Search PubMed⌕ Search

Biomedical subjects

I A Greer

Publications and source records attributed to I A Greer.

At least 37 records · Page 2Linked to original sources

The acute management of venous thromboembolism in pregnancy.

Pulmonary thromboembolism is the leading cause of maternal death in the UK. Optimal management of deep venous thrombosis and pulmonary thromboembolism requires an appreciation of risk factors, particularly thrombophilia, and signs or symptoms suggestive of venous thromboembolism, along with objective diagnosis and treatment with anticoagulants. Low molecular weight heparins are now replacing unfractionated heparin for the treatment of deep venous thrombosis and pulmonary thromboembolism in pregnancy because of the lower risk of side effects, ease of administration and reduced need for monitoring.

Anticoagulants↗

A comparison of isosorbide mononitrate, misoprostol and combination therapy for first trimester pre-operative cervical ripening: a randomised controlled trial.

OBJECTIVE: To determine whether a combined therapy with isosorbide mononitrate (40mg) and misoprostol (400 microg) for pre-operative cervical ripening in the first trimester would result in improved clinical effectiveness, and fewer side effects compared with each agent used alone. DESIGN: Randomised controlled trial. SETTING: Glasgow Royal Infirmary. POPULATION: Sixty-six primigravid women scheduled for suction termination of pregnancy. METHODS: Women were randomly assigned to receive before surgery, per vaginam, isosorbide mononitrate 40 mg (n = 22), misoprostol 400 microg (n = 22) or both agents together [isosorbide mononitrate 40 mg and misoprostol 400 microg] (n = 22). MAIN OUTCOME MEASURES: 1. To assess the cumulative force required to dilate the cervix to 8 mm; 2. the onset of new symptoms before termination of pregnancy. RESULTS: The cervical resistance following combination therapy with isosorbide mononitrate and misoprostol was not significantly different than following misoprostol alone [24.5N vs 18.5N; median difference (95% CI) 19N (-22 to 49)]. Pre-treatment with misoprostol used alone resulted in a lower cervical resistance than isosorbide mononitrate alone (18.5N vs 39N, P = 0.04, Mann-Whitney U test). There was no difference in the number of women remaining asymptomatic following either isosorbide mononitrate or misoprostol or combination therapy [14/22 (64%) vs 11/21 (52%) vs 11/22 (50%), Fisher's exact test]. CONCLUSIONS: We have not shown any advantage of combining misoprostol with the nitric oxide donor isosorbide mononitrate compared with misoprostol alone for pre-operative cervical ripening in the first trimester.

Abortifacient Agents, Nonsteroidal↗

The effect of type 1 diabetes mellitus on vascular responses to endothelin-1 in pregnant women.

Diabetes is associated with vascular dysfunction, which may be due in part to altered vascular responses to endogenous peptides such as endothelin-1. These altered responses may also contribute to the decreased maternal peripheral resistance in pregnancy. The aim of this study was to examine the effect of diabetes on the vasoconstrictor response to endothelin-1 in pregnant women. Small arteries were isolated from nine healthy pregnant, seven type 1 diabetic pregnant women, and five healthy nonpregnant women. Contraction curves were performed on a wire myograph for noradrenaline (1 nM to 30 microM) and endothelin-1 (1 pM to 0.3 microM). Maximum responses and sensitivity were compared by t test. No differences in maximum response to noradrenaline or potassium were seen among the three groups. The maximum response to endothelin-1 was significantly increased in pregnancy (P < 0.05), whereas endothelin-1 sensitivity was reduced in the diabetic compared with the nondiabetic pregnant women (P < 0.05). Pregnant women have an increased maximum vasoconstriction response to endothelin-1 compared with nonpregnant women, whereas diabetic pregnant women demonstrate reduced sensitivity to endothelin-1. These observations suggest that endothelin-1 may play a role in maintaining peripheral vascular tone in normal pregnancy, and the decreased sensitivity seen in pregnant women with diabetes may reflect abnormal vascular reactivity.

Adult↗

Circulating leptin concentrations and ovarian function in polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is characterized by ovarian dysfunction. Although the role of leptin in the control of reproduction is unclear, it may be involved in the control of ovulation. The aim of this cross-sectional study was to determine the relationship between circulating leptin concentrations, and anthropometric, metabolic and endocrine variables as well as to examine a possible role of leptin in ovarian dysfunction associated with PCOS. DESIGN: Prospective observational study. METHODS: Seventy-one subjects with PCOS and 23 body mass index (BMI)-matched control subjects were recruited from infertility clinics. The association between serum leptin concentrations and the above variables was measured outwith the luteal phase. A subgroup of 24 PCOS subjects underwent more frequent blood sampling to monitor follicular growth and ovulation. The association between variables was measured by univariate, multivariate and partial correlation analyses. RESULTS: Serum leptin concentrations were not different in subjects with PCOS and controls, and were strongly associated with BMI in both groups. Twelve patients ovulated during the study period. There was no significant difference in serum leptin concentrations between ovulatory and anovulatory subjects. The relationship between BMI and leptin was similar in both groups. CONCLUSION: The results indicated that circulating leptin concentrations relate principally to total body fat in subjects with PCOS and controls, and that this is not associated with the facility for follicular development and ovulation in these patients.

Adult↗

The Glasgow Outcome, APCR and Lipid (GOAL) Pregnancy Study: significance of pregnancy associated activated protein C resistance.

Activated protein C (APC) resistance secondary to Factor V Leiden (FVL) is associated with pregnancy failure and pre-eclampsia (PET). In non-pregnant subjects, the degree of resistance to APC relates to venous thrombosis risk. In pregnancy, resistance to APC occurs in the absence of FVL. We investigated, in an unselected prospective longitudinal study of 1,671 pregnant, non-FVL subjects, the relationship of the APC sensitivity ratio (APC:SR) with demographic variables and pregnancy outcome. Lower APC:SR values at 7-16 weeks gestation were observed in subjects who subsequently developed PET (median APC:SR 2.55, IQR 2.29-2.70 vs 2.69, IQR 2.48-2.93, Mann-Whitney U-test p = 0.003) in the current pregnancy. An APC:SR < the median (2.69) at 7-16 weeks was associated with a 2.95-fold increased risk (CI95 1.2-7.4) of PET in the current pregnancy. No relationship between the APC:SR, at any gestation, and fetal loss was observed. An inverse correlation between the APC:SR and birth weight was noted. Higher APC:SRs were observed in blood group O subjects and smokers. An inverse relationship of the APC:SR with age, diastolic blood pressure and total serum cholesterol was observed.

Abortion, Spontaneous↗

Lipoprotein (a) levels in normal pregnancy and in pregnancy complicated with pre-eclampsia.

Lipoprotein (a) (Lp(a)) is recognised as a risk factor for arterial and venous thrombosis, a property which may relate to its structural similarity to plasminogen. Pregnancy is associated with a hypofibrinolytic state. Elevated Lp(a) may influence fibrinolysis and have an unfavourable role in pregnancy outcome. In this study alterations in plasma Lp(a) concentrations during normal pregnancy was examined, in a detailed longitudinal investigation, in ten women together with changes in other lipid parameters. In addition, Lp(a) concentrations were examined in subjects with pre-eclampsia (n=10) relative to matched controls (n=10), since it has recently been reported that a substantial increase in circulating Lp(a) occurs in this disorder. Lp(a) concentration increased steadily in normal pregnancy between 10 and 35 weeks with a doubling of the median value from 14.5 to 27.0 mg/dl (P=0.01). A significant increase in Lp(a) values was observed in all subjects with increasing gestation (median rise 190%, range 117-340%). This increase was intermediate to those seen in plasma triglyceride and cholesterol. No significant difference in Lp(a) values was observed in subjects with pre-eclampsia, compared with matched normal pregnancy controls (median 14 mg/dl [IQR 4.7-69.0] in pre-eclampsia vs 20 mg/dl [9.0-56. 3] in controls; P=0.57), at a median gestation of 32 weeks. In conclusion, there is a 2-fold increase in Lp(a) during normal pregnancy, which may influence fibrinolysis. Circulating Lp(a) is not significantly elevated in women with pre-eclampsia, and thus is unlikely to play a role in the pathophysiology of this disorder.

Adult↗

Prevalence of the post-thrombotic syndrome in young women with previous venous thromboembolism.

The prevalence of mild, moderate and severe post-thrombotic syndrome (PTS) among 43 young women with a previous single episode of deep vein thrombosis (DVT) was 67%, 7% and 0% respectively. Subjects were assessed at a mean 51 months after the event. Moderate PTS was more common in women with recurrent (n = 9) DVT (44%, P < 0.001). Chronic venous insufficiency, assessed by light reflection rheography (LRR), was significantly (P < 0.05) more prevalent in women with single previous DVT (n = 40), recurrent DVT (n = 9) and isolated pulmonary embolism (PE) (n = 19) compared with healthy age-matched controls (odds ratios 10.9, 52.4 and 3.8 respectively). LRR findings correlated with moderate, but not mild, PTS. There was no correlation between development of PTS and body mass index.

Adolescent↗

Non-haemorrhagic obstetric shock.

The causes of non-haemorrhagic obstetric shock (pulmonary thromboembolism, amniotic fluid embolism, acute uterine inversion and sepsis) are uncommon but responsible for the majority of maternal deaths in the developed world. Clinically suspected pulmonary thromboembolism should be treated initially with heparin and objective testing should be performed. If the diagnosis is confirmed, heparin is usually continued until delivery, following which anticoagulation in the puerperium is achieved with either warfarin or heparin. Amniotic fluid embolism is a rare complication of pregnancy, occurring most commonly during labour. The management of amniotic fluid embolism involves maternal oxygenation, the maintenance of cardiac output and blood pressure, and the management of any associated coagulopathy. Acute uterine inversion arises most commonly following mismanagement of the third stage of labour. The shock in uterine inversion is neurogenic in origin, although there may also be profound haemorrhage. The management of this condition includes maternal resuscitation and replacement of the uterus either manually, surgically or by hydrostatic pressure. Genital tract sepsis remains a significant cause of maternal death, the most common predisposing factor being prolonged rupture of the fetal membranes. The management of septic shock in pregnancy includes resuscitation, identification of the source of infection and alteration of the systemic inflammatory response.

Adolescent↗

Changes in the expression of nitric oxide synthase in the human uterine cervix during pregnancy and parturition.

Nitric oxide (NO) has been proposed as a mediator of cervical ripening. We investigated the expression, using Western blotting, and localization, using immunohistochemistry, of the nitric oxide synthase (NOS) enzymes, inducible NOS (iNOS), endothelial NOS (eNOS) and neuronal NOS (bNOS) in the human cervix during pregnancy and parturition. Cervical biopsies were obtained from non-pregnant women, women in the first trimester of pregnancy, and pregnant women at term before and after the onset of labour. Each of the NOS isoforms was localized in the cervices of both non-pregnant and pregnant subjects using immunohistochemistry. iNOS expression was significantly greater in early pregnancy compared with the non-pregnant state (P: < 0.005). iNOS expression was up-regulated further in samples obtained in the third trimester compared with the first trimester. bNOS expression was greater in samples from the first trimester of pregnancy than in non-pregnant samples (P: < 0. 005), but showed no additional increase in late pregnancy or with the onset of labour. eNOS expression was increased in samples obtained in the third trimester both before (P: = 0.002) and after the onset of labour (P: < 0.002) when compared with non-pregnant samples. The increased expression of NOS isoforms in late pregnancy supports the hypothesis that NO is involved in the process of cervical ripening.

Blotting, Western↗

Antenatal use of enoxaparin for prevention and treatment of thromboembolism in pregnancy.

OBJECTIVE: To assess the safety and efficacy of enoxaparin use for thromboprophylaxis or treatment of venous thromboembolism during pregnancy. DESIGN: Retrospective review of casenotes of women who received enoxaparin during pregnancy. SETTING: Obstetric Medicine Unit at Glasgow Royal Maternity Hospital. SAMPLE: Data were obtained on 57 pregnancies in 50 women over six years. METHODS: Information was obtained from case records in relation to outcome measures, the presence of underlying thrombophilia and indication for anticoagulation. MAIN OUTCOME MEASURES: Incidences of venous thromboembolism, haemorrhage, thrombocytopenia, peak plasma anti-factor Xa levels and symptomatic osteoporosis. RESULTS: There were no thromboembolic events in the thromboprophylaxis group. There were no incidences of heparin-induced thrombocytopenia. Twenty-two women had spinal or epidural anaesthesia and no complications were encountered. There was one instance of antepartum haemorrhage following attempted amniotomy in a woman with previously unknown vasa praevia. Two women sustained postpartum haemorrhage, both secondary to vaginal lacerations, resulting in blood loss > 1,000 mL. Blood loss following caesarean section was not excessive. No instances of vertebral or hip fracture were encountered. The median peak plasma anti-factor Xa level on a dose of 40 mg once daily was 0.235 U/mL; peak plasma anti-factor Xa levels were not affected by gestational age. CONCLUSIONS: The use of enoxaparin in pregnancy is associated with a low incidence of complications and a dose of 40 mg once daily throughout pregnancy provides satisfactory anti-factor Xa levels and appears effective in preventing venous thromboembolism.

Adolescent↗

Prothrombin 20210 G-->A, MTHFR C677T mutations in women with venous thromboembolism associated with pregnancy.

Over 50 unselected women with maternal venous thromboembolism were screened for the prothrombin 20210 G-->A and MTHFR C677T mutations, in addition to screening for other thrombophilias. The prevalence of thrombophilia in these women was compared with its prevalence in the general population in our area. The prothrombin (OR 4.4; 95% CI 1.2-16) and factor V Leiden (OR 4.5; 95% CI 2.1-14.5) mutations were more common in our patients, compared with the general population, whereas women homozygous for the C677T mutation in the methylene tetrahydrofolate reductase gene (OR 0.45; 95% CI 0.13-1.58) were not. It is recommended that women with a personal or strong family history of venous thromboembolism should be screened for the prothrombin mutation either before or early in pregnancy, in addition to screening for other thrombophilias. Screening for the MTHFR mutation does not appear to identify women at increased risk of maternal venous thrombosis.

Cohort Studies↗

Lipoprotein (a), cholesterol and triglycerides in women with venous thromboembolism.

Plasma concentrations of lipoprotein (a), total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglyceride were measured in 62 women who had suffered an episode of objectively confirmed venous thromboembolism (VTE) at < or = 50 years of age, and in 98 age-matched female controls. The mean body mass index (BMI) of cases was significantly (P < 0.001) higher than that of controls. Plasma triglyceride was significantly higher, and total cholesterol/LDL- and HDL-cholesterol significantly lower, in cases compared with controls. After adjustment for BMI, the plasma total cholesterol and LDL-cholesterol remained significantly lower in cases. No significant differences in mean plasma lipoprotein (a) levels were identified between cases and controls. Lipoprotein (a) does not appear to be significantly associated with the development of VTE in young women. The increased risk of VTE in obese subjects may be mediated, at least in part, via hypertriglyceridaemia, which has previously been demonstrated to have effects on levels of coagulation factors, natural anticoagulants, and plasminogen activator inhibitor type 1.

Adult↗