Search PubMed⌕ Search

Biomedical subjects

I A Greer

Publications and source records attributed to I A Greer.

At least 73 records · Page 4Linked to original sources
PubMed1998

The neutrophil and preeclampsia.

Endothelial injury is common to all pathological features of preeclampsia. Neutrophil activation has been implicated in the pathophysiology of preeclampsia and requires binding and transmigration of neutrophils through the endothelium. This occurs via an interaction of endothelial adhesion molecules and surface receptors on neutrophils. Upon activation, neutrophil granules are released, the contents of which are capable of mediating vascular damage. In addition, leukotrienes are synthesized, and superoxide is generated in a respiratory burst. These products also provoke vascular damage. Neutrophil recruitment to the endothelium involves express of P-selectin and released of platelet activating factor from the endothelium. In preeclampsia there is evidence of an increase in neutrophil activation with up-regulation of neutrophil integrin expression and increased regulation of the protease elastase. Furthermore, these markers of neutrophil activation correlate with established markers of disease severity. The primary mechanism of neutrophil activation is unknown, but neutrophils in preeclampsia appear to have normal motor activity. Several potential mechanisms of neutrophil activation have been identified. They include up-regulation of cellular adhesion molecules on the endothelial surface, increased generation of tumor necrosis factor-alpha, and endothelial activation from hyperlipidemia. In additional to activation of neutrophils in preeclampsia, there may be involvement of the interleukin-6 and endothelin-1 in "priming" neutrophils for subsequent superoxide production. Activated neutrophils are likely to play a large part in the arteriopathy and endothelial damage associated with preeclampsia, but it is unclear whether neutrophil activation is the cause or the consequence of endothelial damage.

Biomarkers↗
PubMed1998

Effects of ketorolac and dextran-70 alone and in combination on haemostasis.

BACKGROUND: Dextran may be used in surgical patients for thromboprophylaxis or volume expansion along with ketorolac, a nonsteroidal anti-inflammatory drug, for analgesia. As these two agents can influence the haemostatic system at different sites, it is important to demonstrate that there is no adverse haemostatic interaction between them. METHODS: The haemostatic interaction between intravenous dextran-70 and intramuscular ketorolac was assessed in a double-blind, randomised, crossover study of healthy male volunteers each given all four combinations of ketorolac/placebo intramuscularly and dextran/placebo intravenously. The effect of ketorolac and dextran on haemostasis was assessed by the following techniques: skin bleeding time, in vitro platelet aggregation function, whole blood thromboxane generation, von Willebrand factor antigen, factor VIII coagulant activity and tissue plasminogen activator. The results were analysed for the effects of ketorolac and dextran and for any evidence of an interaction. RESULTS: Ketorolac inhibited platelet function and thromboxane generation. Dextran reduced factor VIII coagulant activity. Neither agent had a significant effect on bleeding time, von Willebrand factor or tissue plasminogen activator. There was only evidence of a small but statistically significant interaction between ketorolac and dextran on thromboxane generation. There was no evidence of any other interaction of ketorolac with dextran. CONCLUSION: This interaction on thromboxane generation is unlikely to be of clinical significance as substantial inhibition of thromboxane generation occurs with ketorolac alone.

Adult↗
PubMed1998

Puerperal thromboprophylaxis: comparison of the anti-Xa activity of enoxaparin and unfractionated heparin.

Low molecular weight heparins are used extensively for thromboprophylaxis. The aim of this study was to compare the activity of the low molecular weight heparin, enoxaparin, 20 mg and 40 mg, given once per day with unfractionated heparin, 7500iu given twice per day, in terms of their anti-Xa activity in puerperal women following caesarean section and with an additional risk factor for venous thromboembolism. Seventeen women were randomised to receive one of the three treatments. The anti-Xa activity associated with each treatment was measured prior to treatment and at 2, 4, 6, 12 and 24 hours. The mean anti-Xa values of the groups receiving enoxaparin, 20 mg and 40 mg, were significantly higher than those of the group receiving unfractionated heparin. There was no difference between the two enoxaparin groups in terms of the anti-Xa activity profiles. This study suggests that the use of enoxaparin is superior to unfractionated heparin in terms of anti-Xa activity.

Anticoagulants↗
PubMed1998

The special case of venous thromboembolism in pregnancy.

Pulmonary thromboembolism remains a major cause of maternal death in the Western world. The frequency of antepartum deaths, including deaths in the first and second trimester, which can be associated with early pregnancy problems such as hyperemesis, is similar in number to the deaths occurring following delivery. Risk factors for deep vein thrombosis have been identified and include age > 35 years, operative delivery (particularly emergency Caesarean section), obesity and a personal or family history of thrombosis or thrombophilia. These risk factors should be used to guide administration of thromboprophylaxis during both pregnancy and the post-partum period, particularly after Caesarean section. Specific consideration towards thromboprophylactic agents is required. Warfarin crosses the placenta, is a known teratogen when used in early pregnancy and can also be associated with bleeding problems in the foetus, particularly at the time of delivery. Thus, warfarin has a limited use in the antenatal period and is usually only employed in patients such as those with artificial heart valves who require long-term anticoagulation. However, as warfarin does not cross the breast in any significant amount, it is suitable during breast feeding. In contrast, heparin does not cross the placenta or the breast therefore foetal problems are not associated with this treatment. However, heparin can be associated with problems such as heparin-induced osteoporosis, allergy and heparin-induced thrombocytopenia. The risk of some of these complications can be reduced by the use of low-molecular-weight heparins. When venous thromboembolism is suspected in pregnancy, it is critically important to obtain an objective diagnosis. This will include real-time or duplex ultrasound scan of the legs to elaborate the venous system, ventilation perfusion lung scan and, occasionally, venography. Treatment of established venous thromboembolism is similar to that in the non-pregnant patient and it is likely that low-molecular-weight heparins will play a major role in thromboprophylaxis in the future.

Adult↗
PubMed1998

Increased nitrotyrosine in the diabetic placenta: evidence for oxidative stress.

OBJECTIVE: To evaluate the presence of nitrotyrosine (NT) residues in placental villous tissue of diabetic pregnancies as an index of vascular damage linked to oxidative stress. RESEARCH DESIGN AND METHODS: Villous tissue was collected and flash frozen after delivery from 10 class C and D IDDM patients (37.9+/-3.2 weeks) and 10 normotensive pregnant individuals (37.5+/-3.8 weeks). Serial sections of tissue were immunostained with specific antibodies to NT, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and manganese superoxide dismutase (MnSOD). Sections were scored for intensity of immunostaining (0-3) by three observers blinded to the identity of tissue. RESULTS: All tissues demonstrated immunostaining for eNOS in both syncytiotrophoblast and stem villous vascular endothelium with no apparent differences between groups. Immunostaining for iNOS was seen in the villous stroma, but again was not different between the two groups. Significantly more intense NT staining was apparent in vascular endothelium and villous stroma (both P < 0.02) of diabetic placentas. The endothelium of large villous vessels of diabetic tissues also showed more intense immunostaining for MnSOD (P < 0.01). CONCLUSIONS: In these diabetic pregnancies, we were unable to show increased eNOS, unlike previous findings in preeclamptic pregnancies. The presence of NT may indicate vascular damage in the diabetic placenta due to peroxynitrite action formed from increased synthesis/interaction of nitric oxide and superoxide. The apparently paradoxical increase in MnSOD expression may be an adaptive response to increased superoxide generation.

Biomarkers↗
PubMed1998

Leptin levels in pregnancy: marker for fat accumulation and mobilization?

BACKGROUND: Leptin, an adipose tissue-derived signalling factor encoded by the obese gene has been shown to be present as a 16-kDa protein in the blood of mice and humans. Resistance to leptin occurs in human obesity. Leptin has also been shown to associate with plasma insulin concentrations and there is currently considerable debate about the potential link between insulin resistance and resistance to leptin. In non-pregnant individuals, circulating leptin concentrations associate strongly with both total body fat mass and body mass index (BMI). In normal human pregnancy, the maternal fat stores increase to a peak in the late second trimester, before declining towards term as fat stores are mobilized to support the rapidly growing fetus. Insulin resistance increases during late pregnancy and is believed to be further enhanced in pregnancies complicated by pre-eclampsia. The aim of this study was to examine if leptin levels were altered in pregnancy and, if so, whether the pattern of change in circulating leptin related to previously established changes in fasting insulin concentrations or fat mass. METHODS: We measured third trimester plasma leptin concentrations in 12 uncomplicated pregnant women, nine women with pre-eclampsia matched for age and booking BMI, and 18 non-pregnant women similarly matched. We also examined the longitudinal course of leptin concentrations occurring throughout gestation (from 10 weeks gestation and at five week intervals thereafter), in five normal pregnancies and two women with gestational-onset diabetes. RESULTS: Leptin concentrations were significantly higher in the normal pregnant women (37.1 microg/L, [15.4-117.0], geometric mean, [range]; p=0.049), and women with pre-eclampsia (45.3 microg/L, [21.3-98.4]; p=0.001), than in non-pregnant controls (17.85 microg/L, [1.3-36.5]), however, there was no significant difference between uncomplicated and pre-eclamptic pregnancies (p=0.22). On examination of the longitudinal course of leptin concentrations occurring throughout gestation, in all seven women plasma leptin concentrations initially increased relative to booking (10 weeks) concentrations, but did so by varying amounts (ranging between 30-233%). Significantly, however, in all seven women plasma leptin concentrations peaked at around 20-30 weeks of gestation before declining towards term. CONCLUSION: On the basis of these observations, we postulate that plasma leptin levels increase significantly in human pregnancies and that the pattern of change in circulating leptin parallels the process of fat accumulation and mobilization.

Adult↗
PubMed1998

Superficial vein thrombosis: incidence in association with pregnancy and prevalence of thrombophilic defects.

Superficial venous thrombotic (SVT) events are a feature of thrombophilic abnormalities, particularly those involving the protein C pathway. We have determined the incidence of SVT associated with pregnancy and the early postpartum period in a retrospective study involving 72000 deliveries. Fourty-nine cases occurring in 47 individuals were recorded, with an overall incidence of 0.68/1000 deliveries (95% CI 0.48-0.88). None had a previous history of deep vein thrombosis or pulmonary embolism. Most events occurred in the early postpartum period (0.54/1000 deliveries). Twenty-four/fourty-seven were screened for established thrombophilic abnormalities, with only 1 abnormality detected (FV(Leiden) heterozygote). Thrombophilia may play a minor role in the aetiology of SVT associated with pregnancy, although a larger study is required to confirm this.

Adult↗
PubMed1998

Activated protein C sensitivity, protein C, protein S and coagulation in normal pregnancy.

A prospective study of activated protein C sensitivity, protein C, protein S, and other coagulation factors in 239 women during normal pregnancy was carried out. Protein C activity appeared unaffected by gestation, although an elevation of protein C activity was observed in the early puerperium. A fall in total and free protein S with increasing gestation was observed. Activated protein C sensitivity ratio (APC:SR) showed a progressive fall through pregnancy. This fall correlated with changes in factor VIIIc, factor Vc and protein S. 38% of subjects, with no evidence of Factor V Leiden or anticardiolipin antibodies, showed a low APC:SR (APC:SR <2.6) in the third trimester of pregnancy. Aside from a significant reduction in birth weight, no difference in pregnancy outcome was observed between these subjects and those with a normal APC:SR. Activated protein C sensitivity ratio, modified by pre-dilution of patient samples with factor V depleted plasma, showed no consistent trend with gestation.

Birth Weight↗
PubMed1997

Lipoprotein subfraction concentrations in preeclampsia: pathogenic parallels to atherosclerosis.

OBJECTIVE: To determine whether large triglyceride-rich lipoproteins, very-low-density lipoprotein1 (VLDL1), and small, dense low-density lipoprotein (LDL-III), are significantly increased in women with preeclampsia compared with concentrations seen in normal pregnancy. METHODS: Plasma concentrations of very-low-density and low-density lipoprotein subfractions and pre-heparin hepatic lipase activity were measured in eight women with preeclampsia and in eight healthy pregnant controls matched for age, gestational age, and weight. RESULTS: Women with preeclampsia exhibited higher median plasma triglyceride concentrations (3.68 versus 1.93 mmol/L, P = .004) compared with controls. This was reflected in an almost threefold increase in median VLDL1 (184 versus 68 mg/dL, P = .002) and a twofold increase in very-low-density lipoprotein2 (VLDL2) (146 versus 76 mg/dL, P = .014), whereas total plasma cholesterol, intermediate-density lipoprotein, and total LDL concentration were the same in subjects and controls. Furthermore, women with preeclampsia demonstrated significantly lower concentrations of the large, buoyant LDL subfractions, LDL-I and LDL-II, and markedly elevated median plasma concentrations of small, dense LDL, LDL-III (170 versus 55 mg/dL, P = .024). High-density lipoprotein-cholesterol concentration also was significantly lower (P = .021), and pre-heparin hepatic lipase activity was significantly elevated (29 versus 18 mumol fatty acids/mL/hour, P = .041) in the preeclamptic group. The concentration of small, dense LDL correlated positively with plasma triglyceride concentration (r2 = 0.504, P = .002). CONCLUSION: Women with preeclampsia exhibit markedly elevated concentrations of triglyceride-rich lipoproteins in the circulation. These particles are potential contributors to endothelial dysfunction and the expression of preeclampsia, both directly and, indirectly, through the generation of small, dense LDL.

Adult↗
PubMed1997

Circulating cell adhesion molecule concentrations in diabetic women during pregnancy.

OBJECTIVE: To determine whether circulating concentrations of defined cell adhesion molecules, which are thought to reflect endothelial expression, are increased in insulin-dependent diabetic women during pregnancy. METHODS: Pregnant diabetic women demonstrating good glycemic control and without major complications before pregnancy were studied at 8-12 (n = 15), 18 (n = 15), 28 (n = 16), 32 (n = 16), and 36 (n = 16) weeks' gestation. A subgroup of ten diabetic women was sampled longitudinally through all five gestational ages. The diabetic women were compared with healthy nondiabetic women sampled cross sectionally at 12 (n = 20), 28 (n = 19), and 36 (n = 19) weeks' gestation. Nonpregnant diabetic (n = 22) and nonpregnant nondiabetic women (n = 28) also were studied. Plasma concentrations of the cell adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular endothelial cell adhesion molecule-1 (VCAM-1) were measured by enzyme-linked immunosorbent assay. RESULTS: Significantly higher median (range) concentrations of E-selectin (63.0 [20.2-107.0] ng/mL) and ICAM-1 (281.5 [171.6-778.4] ng/mL) but not VCAM-1 (459.7 [301.0-909.7] ng/mL) were found in nonpregnant diabetic women compared with nonpregnant nondiabetic women (43.5 [18.1-93.2], 243.6 [174.4-329.2], and 476.0 [253.8-929.4] ng/mL, respectively). During pregnancy these significant differences between diabetic and control groups were lost. The median (range) concentration of E-selectin (50.0 [21.2-96.3] ng/mL) was significantly lower in pregnant compared with nonpregnant diabetic women. The plasma concentrations of E-selectin and ICAM-1 did not change significantly with gestation in either diabetic or nondiabetic pregnant groups. Vascular endothelial cell adhesion molecule-1 concentration changed significantly with gestation in the diabetic pregnant group only. CONCLUSION: Circulating concentrations of defined vascular cell adhesion molecules are not increased abnormally in diabetic women with good glycemic control during otherwise uncomplicated pregnancy.

Adult↗
PubMed1997

Placental expression of vascular endothelial growth factor in placentae from pregnancies complicated by pre-eclampsia and intrauterine growth restriction does not support placental hypoxia at delivery.

In view of the pathological placental features of pre-eclampsia and intrauterine growth restriction (IUGR), and the angiogenic effects of vascular endothelial growth factor (VEGF), the aim of this study was to determine the expression of VEGF in placentae from normal pregnancies and to compare the results with placentae from pregnancies complicated by pre-eclampsia and intrauterine growth restriction (IUGR). ELISA was used to measure circulating VEGF immunoreactivity in umbilical vein serum samples and immunohistochemistry was used to determine tissue expression of the protein. Since VEGF is known to be upregulated by hypoxia, the expression pattern of VEGF would provide further clues to the oxygen status in the placentae at the time of sampling, presently a subject under great debate. The geometric mean concentration of VEGF immunoreactivity in umbilical vein serum of normal pregnant women was 112.46 pg/ml, in women with pre-eclampsia 50.23 pg/ml and in IUGR alone 175.35 pg/ml. These values were not statistically different from each other. Immunolocalization of VEGF in normal term villous placenta was observed in the syncytiotrophoblast with less intense staining in stromal cells. No qualitative differences in localization of staining between the groups (normal pregnancies, pre-eclampsia, pre-eclampsia plus IUGR, and IUGR) was found. Intensity of staining in stromal cells was also similar in the groups studied. However, intensity of VEGF immunostaining in syncytiotrophoblast was significantly reduced in the three pathological groups (P < 0.02) compared with the control group. These results suggest that reduced VEGF may be responsible, at least in part, for the impaired vascular development which occurs in these conditions. Our results are therefore not consistent with villous placental hypoxia at the time of sample collection.

Adult↗
PubMed1997

Prawn sandwiches, red herrings and abdominal pregnancy.

An unusual presentation of abdominal pregnancy is reported. The difficulty in diagnosis of this form of ectopic pregnancy, and the potential risks of delayed intervention are highlighted. The association with uterine anomaly, in this case uterus didelphys, is discussed.

Adult↗
PubMed1997

Epidemiology, risk factors and prophylaxis of venous thrombo-embolism in obstetrics and gynaecology.

Venous thrombo-embolism remains a major cause of mortality and morbidity following gynaecological surgery and in association with pregnancy and delivery. Specific risk factors can be identified pre-operatively and before or during pregnancy and delivery. Clinicians and units should develop guidelines for risk assessment and the implementation of specific thromboprophylactic measures in patients considered to have significant risk. The main prophylactic techniques are unfractionated and low-molecular-weight heparins and physical methods such as graduated elastic compression stockings. It should be noted that there are particular concerns with regard to the use of pharmacological thromboprophylaxis with both heparin and warfarin in pregnancy. Unfractionated heparin is associated with osteoporotic problems, allergy and heparin-induced thrombocytopenia which can cause significant thrombotic problems. Warfarin is associated with teratogenesis and the risk of bleeding in mother and fetus. Clearly, where antenatal thromboprophylaxis is to be used, the risk of the anticoagulants employed must be weighed against the potential benefits. Such assessment might be best done prior to pregnancy in order that the patient can enter pregnancy with a clear view of the potential hazards and benefits. Low-molecular-weight heparins are being increasingly used in pregnancy but it is unclear to what extent they are safer than unfractionated heparins. However, they do appear to have substantially less risk of heparin-induced thrombocytopenia and possibly less risk of heparin-induced osteoporosis. Increasingly, thrombophilia is recognized as underlying many thrombotic problems, particularly in young women, and when the events occur in association with pregnancy. In view of the complexity in the management of such patients, it is important that they be referred to a unit with specific expertise in the management of thrombophilia.

Cesarean Section↗