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Biomedical subjects

B J Hunt

Publications and source records attributed to B J Hunt.

At least 19 recordsLinked to original sources
PubMed1999

Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial.

BACKGROUND: Oxidative stress has been implicated in the pathophysiology of pre-eclampsia. This randomised controlled trial investigated the effect of supplementation with vitamins C and E in women at increased risk of the disorder on plasma markers of vascular endothelial activation and placental insufficiency and the occurrence of pre-eclampsia. METHODS: 283 women were identified as being at increased risk of pre-eclampsia by abnormal two-stage uterine-artery doppler analysis or a previous history of the disorder and were randomly assigned vitamin C (1000 mg/day) and vitamin E (400 IU/day) or placebo at 16-22 weeks' gestation. Plasma markers of endothelial activation (plasminogen-activator inhibitor 1 [PAI-1]) and placental dysfunction (PAI-2) were measured every month until delivery. Pre-eclampsia was assessed by the development of proteinuric hypertension. Analyses were done by intention to treat, and in the cohort who completed the study. FINDINGS: Supplementation with vitamins C and E was associated with a 21% decrease in the PAI-1/PAI-2 ratio during gestation (95% CI 4-35, p=0.015). In the intention-to-treat cohort, pre-eclampsia occurred in 24 (17%) of 142 women in the placebo group and 11 (8%) of 141 in the vitamin group (adjusted odds ratio 0.39 [0.17-0.90], p=0.02). In the cohort who completed the study (81 placebo group, 79 vitamin group), the odds ratio for pre-eclampsia was 0.24 (0.08-0.70, p=0.002). INTERPRETATION: Supplementation with vitamins C and E may be beneficial in the prevention of pre-eclampsia in women at increased risk of the disease. Multicentre trials are needed to show whether vitamin supplementation affects the occurrence of pre-eclampsia in low-risk women and to confirm our results in larger groups of high-risk women from different populations.

Adult↗
PubMed1999

Markers of endothelial cell activation and injury in childhood haemolytic uraemic syndrome.

Diarrhoea-associated haemolytic uraemic syndrome (D+ HUS) is usually caused by verotoxin-producing Escherichia coli. Histology shows endothelial swelling with localised thrombus. Activation of coagulation and fibrinolysis also occurs. These facts, combined with the knowledge that recovery usually follows within weeks, led us to hypothesise that verotoxin causes localised endothelial cell activation but not injury. Markers of endothelial cell activation and injury were measured serially in 30 children with acute D+ HUS, healthy children, and children receiving chronic dialysis. Interpretation of markers was complicated by the renal dysfunction characteristic of D+ HUS. Nevertheless there was no evidence for endothelial cell injury, as soluble tissue factor levels were not increased and soluble thrombomodulin levels were lower than dialysed controls (P<0.001). In the acute phase, soluble vascular cell adhesion molecule levels were raised above normal (P<0.001), but were lower than dialysed controls (P<0.001), and soluble E-selectin levels were not significantly increased compared with normal controls (P=0.2). Hence, there was no evidence for endothelial cell damage or endothelial cell activation by the time children reached hospital; but this study did not exclude the possibility that endothelial cell activation occurred prior to hospital admission.

Adolescent↗
PubMed1999

Safety of low-molecular-weight heparin in pregnancy: a systematic review.

Unfractionated heparin (UFH) remains the anticoagulant of choice during pregnancy. Low-molecular-weight heparins (LMWH) are an attractive alternative to UFH due to their logistic advantages and their association with a lower incidence of osteoporosis and HIT. We reviewed all published clinical reports concerning the use of LMWH during pregnancy. In addition, participants of an international interest group contributed a cohort of pregnant women treated with LMWH. Pregnancies were divided into two groups; those with and those without maternal comorbid conditions. The number of adverse fetal outcomes and the occurrence of maternal complications were evaluated in the two groups. In the group of women with comorbid conditions (n = 290), 13.4% of the pregnancies were associated with an adverse fetal outcome. In contrast, in the group of women without comorbid conditions (n = 196), 3.1% were associated with an adverse outcome, which is comparable to that seen in the normal population. We conclude that LMWH appear to be a safe alternative to unfractionated heparin as an anticoagulant during pregnancy.

Anticoagulants↗
PubMed1998

Activation of coagulation and fibrinolysis during cardiothoracic operations.

BACKGROUND: During open cardiac operations using cardiopulmonary bypass, there is activation of coagulation and fibrinolysis. We assessed the separate contributions of the surgical procedure itself and cardiopulmonary bypass to this, by studying sequential samples from patients undergoing routine open cardiac operations or thoracic operations without cardiopulmonary bypass. METHODS: Activation of coagulation and the extent of fibrinolysis were measured from sequential samples obtained before the operation to 48 hours after the operation for 7 thoracic patients and 8 cardiac patients. RESULTS: In the thoracic group operation length was shorter (p = 0.002), and there was no significant increase in thrombin-antithrombin III complexes or D-dimers until 24 hours postoperatively. In contrast, there was a highly significant increase in thrombin-antithrombin III complexes (p = 0.0043) and D-dimer levels (p = 0.009) during cardiopulmonary bypass. The increase in fibrinolytic activity was caused by an increase in tissue plasminogen activator (p = 0.013). At 48 hours postoperatively, the cardiac patients had a more hypercoagulable state than thoracic patients with significantly higher levels of thrombin-antithrombin III complexes (p = 0.041) and plasminogen activator inhibitor-1 activity (p = 0.0033). CONCLUSIONS: This study suggests the major activation of coagulation and fibrinolysis seen during cardiac operations is caused by the use of cardiopulmonary bypass.

Adolescent↗
PubMed1998

Complement activation during major surgery: the effect of extracorporeal circuits and high-dose aprotinin.

OBJECTIVE: To assess the in vivo contribution to complement activation of an extracorporeal circuit and the use of high-dose aprotinin during major surgery. DESIGN: Sequential samples were obtained from 8 patients undergoing thoracic surgery, 20 patients undergoing orthotopic liver transplantation (OLT) using venovenous bypass, and 19 patients undergoing cardiac surgery using cardiopulmonary bypass (CPB). INTERVENTION: The latter two groups were part of a randomized controlled trial of high-dose aprotinin. MEASUREMENTS: Total complement activation was measured with the hemolytic complement activity and the C3 activation-specific marker, C3d antigen. MAIN RESULTS: Complement activation did not occur during thoracic surgery. During OLT, C3d antigen levels, expressed as mean +/- standard deviation (SD), were elevated from baseline at skin closure (8.6 +/- 2.5 v 13.0 +/- 5.2 mg/L; p = 0.0082). During cardiac surgery, C3d antigen levels increased 10 minutes after the start of CPB (pre-CPB, 8.0 +/- 1.9 v 14.2 +/- 3.1 mg/L; p = 0.0001) and remained at greater than baseline values postoperatively (8.0 +/- 1.9 v 11.8 +/- 2.3 mg/L; p = 0.002). There was no difference in complement activation in those receiving high-dose aprotinin during OLT or cardiac surgery. Complement activation during cardiac surgery using extracorporeal circulation occurred to a greater extent than during OLT and thoracic surgery. Complement activation during cardiac surgery or OLT was not attenuated by the use of high-dose aprotinin.

Adolescent↗
PubMed1998

Direct activation of factor X by monocytes occurs during cardiopulmonary bypass.

We hypothesized that monocyte procoagulant activity, which includes up-regulation of tissue factor and direct activation of factor X by CD11b. is an activator of coagulation during cardiopulmonary bypass (CPB), because recent studies have cast doubt on the presumption that the surfaces of CPB activate the intrinsic pathway. Sequential samples were taken from 17 patients undergoing cardiac surgery. During CPB a significant increase in thrombin-antithrombin complexes occurred (P < 0.0005). Factor XIIa levels increased (P < 0.005) but remained within the normal range. Total monocyte procoagulant activity was measured and a functional assay was developed to detect direct activation of factor X alone. There was a significant increase in total procoagulant activity on circulating monocytes from the start of CPB (P < 0.005) to which direct factor X activation was a major contributor (P < 0.005). Direct activation of factor X was inhibited by CD11b blocking peptides. Using flow cytometry, up-regulation of monocyte CD11b (P < 0.0005). but not up-regulation of tissue factor, was found on circulating monocytes. Monocytes adherent on the oxygenator fibres showed increased CD11b expression (P < 0.0001), but no tissue factor when assessed by fluorescent image analysis. In conclusion, direct activation of factor X through monocyte CD11b occurs during CPB and appears to contribute to thrombin generation during CPB.

Adult↗
PubMed1998

The effects of alginate and non-alginate wound dressings on blood coagulation and platelet activation.

Alginates are used as haemostats in wound dressings. They act as calcium ion (Ca) donors as they contain mannuronic (M) or guluronic (G) groups with a high Ca content. This study compared the effects of calcium and zinc containing alginates and non-alginate dressings on blood coagulation and platelet activation to determine which was the best haemostat. We showed that alginate materials activated coagulation more than non-alginate materials. The extent of coagulation activation was affected differently by the alginate M or G group composition. It was demonstrated that alginates containing zinc ions had the greatest potentiating effect on prothrombotic coagulation and platelet activation.

Alginates↗