Nitric oxide (NO) regulates blood flow in the human placenta. As increased resistance to blood flow is seen in the fetal-placental vasculature in pregnancies complicated by pre-eclampsia and/or intrauterine growth restriction (IUGR), we examined expression of endothelial nitric oxide synthase (eNOS) in these placentas. Placental villous tissue sections were obtained from normotensive control (n = 5), IUGR alone (n = 5) or pre-eclamptic (with or without IUGR (n = 9) patients, immunostained for eNOS and scored for localization, type (punctate or diffuse) and intensity of eNOS staining in syncytiotrophoblast and placental vessels. The significance of differences was calculated using the Mann-Whitney U-test. No differences in intensity or type of immunostaining in syncytiotrophoblast were seen. Placentas from patients with pre-eclampsia with or without IUGR had a significantly more basal distribution of eNOS in syncytiotrophoblast. eNOS immunostaining was absent in terminal villous capillary and faint in stem villous vessel endothelium of normal placentas, but was intense in the endothelium of both of these types of vessels in the IUGR and pre-eclampsia groups, with significantly greater staining seen in stem vessels of patients with IUGR alone. This increased eNOS expression and hence increased NO production in the fetal-placental vasculature may be an adaptive response to the increased resistance and poor perfusion in these pathological pregnancies.

Human neutrophil elastase may be a major mediator of vascular damage and could contrihutc to the vascular damage seen in women with pregnancy-induced hypertension (PTH). Elevated plasma levels of this substance will reflect neutrophil activation in vivo. To determine neutrophil activation in PIH, we studied 30 normal nonpregnant women, 32 women with normal pregnancies, 19 with mild/ moderate PIH and 16 with severe PIH between 28 and 39 weeks gestation. Plasma neutrophil elastase was measured by radioimniunoassay. 'There was a significantly higher concentration of plasma neutrophil elastase in both mild/moderate and severe PIH than in iiormotensive pregnancies and this may contribute to thc vascular lesion associated with DIH. Concentrations were also significantly higher in normal pregnancy than in non-pregnant women which suggests that neutrophil activation and degranulation are increased in normal pregnancy.Pregnancy-induced hypertension (PUT) remains a leading cause of maternal inortality in the UK (DHSS 1986) and is a major source of perinatal mortality and morbidity. Its precise aetiology remains obscure, but it is charactcrizcd by increased vascular reactivity (Gant r / al. 1973), platelet activation, coagulation changes (Howie 1977) and vascular damage (Robertson & Khong 1986). This last fcature has been termed

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Summary. Three hundred and twenty-two consecutive women aged 16±70 years who presented with objectively confirmed symptomatic venous thromboembolism (VTE) were studied to determine precipitating factors for thrombosis. One hundred and eighty-seven presented with deep vein thrombosis (DVT), 116 with either definite or possible pulmonary embolism (PE) and 19 with both DVT and PE. Injecting drug use (IDU) via femoral vein puncture was a common risk factor for DVT, associated with 21´4% of all cases of DVT and 52´4% of cases of DVT in women under 40 years. All women with drug-related thrombosis presented with DVT. None presented with symptomatic PE. A number of clinically diagnosed DVT associated with IDU were also documented, suggesting that IDU may be the most common risk factor for DVT in our region. DVT associated with IDU presents significant management challenges.Keywords: deep vein thrombosis, injecting drug use, venous thromboembolism, pulmonary embolism.Venous thromboembolism (VTE) remains an important cause of morbidity and mortality, particularly in women. This relates predominantly to female exposure to risk factors for VTE, such as pregnancy (McColl et al, 1997), the oral contraceptive pill (World Health Organization, 1995a, b;Farmer et al, 1997) and hormone replacement therapy (Daly et al, 1996;Grodstein et al, 1996;Perez Gutthann et al, 1997). In Glasgow, injecting drug use (IDU) is prevalent, with injection into the femoral vein a common mode of administration (Makower et al, 1992). Anecdotally, physicians in our area acknowledge that such an injection technique may constitute a risk for development of deep vein thrombosis (DVT). However, the contribution of IDU to the development of VTE has received little attention to date.The aims of our study were to document risk factors for VTE in a cohort of consecutive women aged 16±70 years diagnosed with either DVT and/or pulmonary embolism (PE) and who were treated at one of two Glasgow hospitals between 1993 and 1997, to determine the contribution of IDU to the development of VTE. PATIENTS AND METHODSPatients. Consecutive women aged 16±70 years who had a hospital discharge diagnosis of DVT or PE and who were treated at one of two Glasgow hospitals between 1993 and 1997 were the subject of study.Diagnosis. All case notes were examined to identify risk factors and details of diagnosis and treatment. The diagnosis of DVT was accepted if confirmed using compression or duplex Doppler ultrasound scanning or contrast venography. For PE, we accepted a high probability ventilationperfusion (V/Q) scan as definite evidence of PE. A diagnosis of possible PE was made where the V/Q scan was of intermediate probability and patients were treated with at least 6 months anticoagulation. The case-note search identified a large number of women who were ID users who had developed apparent DVT. Many such cases were diagnosed clinically; this data is also presented.Statistical techniques. Normally distributed patient characteristics were assessed by using the Student's t-test. ...

Summary. Human neutrophil elastase may be a major mediator of vascular damage and could contribute to the vascular damage seen in women with pregnancy‐induced hypertension (PTH). Elevated plasma levels of this substance will reflect neutrophil activation in vivo. To determine neutrophil activation in PIH, we studied 30 normal nonpregnant women, 32 women with normal pregnancies, 19 with mild/moderate PIH and 16 with severe PIH between 28 and 39 weeks gestation. Plasma neutrophil elastase was measured by radioimmuno‐assay. There was a significantly higher concentration of plasma neutrophil elastase in both mild/moderate and severe PIH than in normotensive pregnancies and this may contribute to the vascular lesion associated with PIH. Concentrations were also significantly higher in normal pregnancy than in non‐pregnant women which suggests that neutrophil activation and degranulation are increased in normal pregnancy.

SummaryA randomised double-blind controlled study was performed to examine the effect of diclofenac on skin bleeding time and in vitro whole blood platelet aggregation. Twenty thoracotomy patients were studied; I0 were given diclofenac 75 mg intramuscularly at induction of anaesthesia, and I0 formed a control group. Skin bleeding times and platelet aggregation tests were performed the day before and repeated one hour after induction of anaesthesia. Diclofenac prolonged skin bleeding time and reduced platelet aggregation. There were no significant changes in the control group. Key wordsAnalgesics; diclofenac. Blood; coagulation.The use of nonsteroidal anti-inflammatory drugs (NSAIDs) to provide postoperative analgesia is becoming accepted practice. Intramuscular diclofenac was shown to be an effective analgesic,' but there is concern over the perioperative use of the NSAIDs since they have potential side effects related to their mechanism of action, inhibition of the enzyme cyclo-oxygenase.2 This enzyme is essential in platelets for the production of thromboxane A, which is an important mediator of platelet aggregation and vasoconstriction. These are processes that constitute the primary haemostatic response to vessel injury. Peri-operative administration of a NSAID could affect platelet function and inhibit haemostasis.It is clear that NSAIDs and aspirin, which has a similar inhibitory effect on cyclo-oxygenase, inhibit aggregation and prolong bleeding time in v~lunteers,~,~ but there is little information on the peri-operative situation where the haemostatic response may be altered by the stress of surgery. It has recently become possible to study platelet aggregation in whole b l~o d .~.~ This may be more physiological than traditional turbidometric methods using platelet-rich plasma, since the platelets are left in their natural milieu surrounded by red and white cells that can influence the aggregatory respon~e.~.~ To our knowledge there is no previous study which uses the whole blood aggregation technique to investigate the effect of NSAIDs on platelet aggregation in the peri-operative situation. The aim of this study was to investigate the effect of intramuscular diclofenac on skin bleeding time and whole blood platelet aggregation in a randomised, double-blind, controlled, peri-operative study. MethodsTwenty ASA 1 and 2 patients aged 27 to 79 years undergoing thoracotomy were studied. The investigation was approved by the regional ethics committee and each subject provided written informed consent before enrolment. Exclusion criteria consisted of a history of peptic ulcer disease, bleeding tendency, asthma, allergies, recent aspirin or NSAID ingestion, and alcohol or narcotic abuse. The general anaesthetic technique was standardised (premedication, papaveretum and hyoscine; induction, thiopentone, suxamethonium; maintenance, nitrous oxide, oxygen, enflurane, fentanyl, alcuronium). Subcutaneous heparin (2500 IU subcutaneously, one hour before operation) was given as prophylaxis against venous thrombosis. A...

Venous thromboembolism (VTE) is the leading cause of maternal mortality in the UK and is also a major cause of long-term morbidity. Recent UK national guidelines recommend thromboprophylaxis, which includes the use of graduated compression stockings (GCS), for high-risk women to reduce the risk of VTE in both the antenatal and postpartum period. This study of 17 women examined the effects of GCS on the deep venous system in the immediate postpartum period and found a statistically significant reduction in the diameter of the common femoral vein (

The purpose of this study was to determine the relaxant effects in vitro of two nitric oxide donors, glyceryl trinitrate and sodium nitroprusside, which are currently available for use in vivo, on contractions of non-labouring myometrium from pregnant women. Since nitric oxide also mediates relaxation by increasing the concentration of cGMP, sensitivity to 8-bromo-cGMP (a cGMP analogue) was also determined. The effects of the K(+)-channel opener lemakalim and of the Ca(2+)-channel blocker nifedipine were studied for comparison. After the addition of glyceryl trinitrate (0.1-100 mumol l-1), sodium nitroprusside (0.1-100 mumol l-1) or 8-bromo-cGMP (0.001-3 mmol l-1), the spontaneous rhythmic contractility of myometrial strips was inhibited in a concentration-dependent manner: the maximum inhibition produced by the highest tested concentration of each drug was 40 +/- 7%, 53 +/- 8% and 39 +/- 8% of the original degree of contraction, respectively. Myometrial contractions were completely abolished by lemakalim and by nifedipine and verapamil at concentrations of > or = 10(-5) mol l-1. The nitric oxide donors, glyceryl trinitrate and sodium nitroprusside, attenuate myometrial contractions and are therefore useful as tocolytic agents. However, at equimolar concentrations in vitro, the ability of glyceryl trinitrate and sodium nitroprusside to attenuate myometrial contractions is less than that of lemakalin, nifedipine and verapamil. Controlled trials are required to determine the side-effects and clinical efficacy of each of these agents in vivo.