Biomedical subjects

V A Holmes

Publications and source records attributed to V A Holmes.

4 recordsLinked to original sources

PubMed2005

Haemostasis in normal pregnancy: a balancing act?

Pregnancy is a risk factor for venous thrombosis and the incidence of venous thromboembolism during normal pregnancy is 6-fold higher during pregnancy than in the general female population of child-bearing age. This incidence is, however, remarkably low given the increases in markers of haemostatic activation observed during normal pregnancy. During normal healthy pregnancy there are substantial changes in the haemostatic system, many of which are procoagulant and supposed to be in preparation for the haemostatic challenge of delivery. Normal haemostasis requires a balance between coagulation and fibrinolysis to maintain the integrity of the vasculature, and complex physiological changes are evident during pregnancy which appear to ensure a constant coagulation/fibrinolysis balance. This balance is maintained, at least partly, by an increase in fibrinolytic activity, but decreases in other factors such as factor XI and monocyte tissue factor expression may also serve to counterbalance procoagulant changes.

Anticoagulants↗

PubMed2004

The Diabetes and Pre-eclampsia Intervention Trial.

OBJECTIVE: Rates of pre-eclampsia in women with type 1 diabetes are two to four times higher than in normal pregnancies. Diabetes is associated with antioxidant depletion and increased free radical production, and an increasing body of evidence suggests that oxidative stress and endothelial cell activation may be relevant to disease pathogenesis in pre-eclampsia. The Diabetes and Pre-eclampsia Intervention Trial (DAPIT) aims to establish if pregnant women with type 1 diabetes supplemented with vitamins C and E have lower rates of pre-eclampsia and endothelial activation compared with placebo treatment. METHODS: DAPIT is a randomised multicentre double-blind placebo-controlled trial that will recruit 756 pregnant women with type 1 diabetes from 20 metabolic-antenatal clinics in the UK over 4 years. Women are randomised to daily vitamin C (1000 mg) and vitamin E (400 IU) or placebo at 8-22 weeks of gestation until delivery. Maternal venous blood is obtained at randomisation, 26 and 34 weeks, for markers of endothelial activation and oxidative stress and to assess glycaemic control. The primary outcome of DAPIT is pre-eclampsia. Secondary outcomes include endothelial activation (PAI-1/PAI-2) and birthweight centile.

Ascorbic Acid↗

PubMed2003

Plasma levels of the immunomodulatory cytokine interleukin-10 during normal human pregnancy: a longitudinal study.

Pregnancy is proposed to be a Th2 phenomenon, where Th2 cytokines inhibit Th1 responses to improve foetal survival. The importance of interleukin-10 (IL-10), an immunomodulatory cytokine produced by Th2 cells, in the maintenance of normal pregnancy is becoming increasingly apparent. In a longitudinal case-control study, the physiological effect of pregnancy on plasma IL-10 was investigated. The plasma concentration of IL-10 was determined using an ELISA technique in 99 pregnant women sampled at 12, 20 and 35 weeks of gestation, 38 non-pregnant control subjects sampled in parallel and in a subgroup of women sampled at 3 days post-partum (n, pregnant 21, non-pregnant 21). Plasma IL-10 was significantly higher in pregnant women at 12, 20 and 35 weeks of gestation (p<0.05, p<0.01 and p<0.0001, respectively), and in mothers post-delivery (p<0.01) when compared to non-pregnant control subjects. Furthermore, there was no significant effect of gestational time on IL-10 concentration. Results from the current study suggest that elevated IL-10 is a physiological consequence of normal healthy pregnancy. These findings help clarify previous conflicting results and establish a range for plasma levels of IL-10 in normal healthy pregnancy.

Adjuvants, Immunologic↗

PubMed2002

Soluble P-selectin levels during normal pregnancy: a longitudinal study.

OBJECTIVE: To investigate soluble P-selectin (sP-selectin) levels and platelet parameters in normal pregnant women compared with non-pregnant control subjects. DESIGN: A longitudinal case-control study. SETTING: Obstetric outpatient clinic in the Jubilee Maternity Hospital, Belfast. POPULATION: One hundred and twenty normal pregnant women and 41 non-pregnant age-matched control subjects. METHODS: The plasma concentration of sP-selectin in pregnant women sampled at 12, 20 and 35 weeks of gestation, and, in a subgroup at three days postpartum, and non-pregnant controls sampled in parallel, was determined using a commercial quantitative sandwich immunoassay kit. Platelet parameters on each blood sample were also recorded using a SYSMEX SE 9500 analyser. MAIN OUTCOME MEASURES: Plasma sP-selectin as a measure of platelet activation in normal pregnancy. RESULTS: Soluble P-selectin was significantly higher in pregnant women than in non-pregnant control subjects at 20 and 35 weeks of gestation, (P < 0.01, and P < 0.001, respectively). Correlation analyses showed positive correlation between sP-selectin and platelet count in pregnant women at 20 and 35 weeks of gestation (r = 0.247, P < 0.05 and r = 0.360, P < 0.001, respectively). Soluble P-selectin concentration per platelet was also significantly higher in pregnant women than in non-pregnant control subjects at 20 and 35 weeks of gestation (P < 0.001). CONCLUSIONS: Our results show that sP-selectin concentration is significantly higher in the second and third trimester of pregnancy when compared with non-pregnant control subjects sampled in parallel. This finding clarifies previous conflicting results on platelet activation in normal pregnancy, and is in agreement with those earlier studies which reported, using other methods, increased platelet activation in normal pregnancy.

Adolescent↗