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Biomedical subjects

A Franx

Publications and source records attributed to A Franx.

At least 19 recordsLinked to original sources
PubMed2006

Acute activation of the endothelium results in increased levels of active von Willebrand factor in hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome.

BACKGROUND: HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome is a severe complication of pre-eclampsia in pregnancy, characterized by microvascular platelet thrombi. Activation of the endothelium is thought to play a key role in pre-eclampsia and HELLP syndrome. Activation of endothelial cells may lead to release of von Willebrand factor (VWF) multimers, which are highly reactive with platelets. Normally, newly released multimers are cleaved by ADAMTS13, resulting in less reactive derivatives. OBJECTIVE: We hypothesized that HELLP syndrome is characterized by increased amounts of active VWF compared with healthy pregnancy and pre-eclampsia, due to acute activation of endothelial cells. This might contribute to thrombocytopenia and thrombotic microangiopathy. METHODS: Active VWF and ADAMTS13 activity were measured in healthy pregnant volunteers (n = 9), patients with pre-eclampsia (n = 6) and patients with HELLP syndrome (n = 14) at similar gestational ages. To study the role of endothelial cell activation, the propeptide/mature VWF ratio was determined, and VWF released by cultured endothelial cells was analyzed. RESULTS: Active VWF levels were increased 2.1-fold in HELLP syndrome compared with healthy pregnant volunteers (P < 0.001) and 1.6-fold compared with patients with pre-eclampsia (P = 0.001). ADAMTS13 activity was moderately decreased in patients with HELLP syndrome compared with healthy pregnant volunteers (P < 0.004), but not compared with patients with pre-eclampsia. The propeptide/mature VWF ratio was increased 1.7-fold compared with healthy pregnant volunteers (P < 0.001) and 1.5-fold compared with patients with pre-eclampsia (P < 0.05). A significant correlation was found between this ratio and the activation factor of VWF (r = 0.68, P < 0.001). The amount of active VWF was increased 1.4-fold in medium of stimulated endothelial cells when compared with non-stimulated cells (P < 0.05). CONCLUSION: Acute endothelial cell activation in HELLP syndrome and decreased ADAMTS13 activity result in increased amounts of active VWF. This might explain the consumptive thrombocytopenia and thrombotic microangiopathy associated with HELLP syndrome. Inhibition of circulating active VWF could be a potential new approach in the treatment of patients with HELLP syndrome.

ADAM Proteins↗
PubMed2006

[Pregnancy complications as a risk factor for metabolic and cardiovascular disease in later life].

In recent years several large epidemiological studies have been published that demonstrate that women who experience gestational diabetes, pregnancy-induced hypertension or pre-eclampsia have an increased risk of developing type-2 diabetes mellitus and cardiovascular disease. 15-50% of women who experience gestational diabetes develop type-2 diabetes mellitus; the risk is particularly high in those who require insulin therapy during pregnancy. - Chronic hypertension frequently develops years after a pregnancy complicated by pregnancy-induced hypertension, especially in women who have had pregnancy-induced hypertension in multiple pregnancies. Women who experience pre-eclampsia in the first 36 weeks of pregnancy or in multiple pregnancies have an increased risk of cardiovascular morbidity and mortality in later life. Therefore gestational diabetes, pregnancy-induced hypertension and pre-eclampsia provide an opportunity to identify individuals with an increased risk of type-2 diabetes mellitus and cardiovascular disease at an early age. This may create new perspectives on prevention.

Adult↗
PubMed2006

Prenatal ultrasonographic prediction of the umbilical coiling index at birth and adverse pregnancy outcome.

OBJECTIVES: To evaluate whether the antenatal umbilical coiling index (aUCI) as measured by ultrasonography predicts the postnatal umbilical coiling index (pUCI) and adverse pregnancy outcome. METHODS: In a prospective study in 117 pregnancies, the aUCI was measured between 28 weeks and term by ultrasonography. The aUCI was calculated as the reciprocal value of the mean pitch of one complete coil. The pUCI was calculated as the number of coils divided by the cord length in cm. The correlation between aUCI and pUCI was assessed and likelihood ratios for adverse pregnancy outcome were calculated. RESULTS: We had complete data on 81 subjects. Mean aUCI +/- SD was 0.30 +/- 0.09 and mean pUCI +/- SD was 0.17 +/- 0.08. The correlation coefficient between aUCI and pUCI was 0.66, P < 0.001. Limits of agreement were 0-0.28 coils/cm. The positive likelihood ratio for small-for-gestational-age infants was 2.6 (95% confidence interval (CI) 0.6-11.6) for ultrasound hypocoiling, and 5.7 (95% CI 1.3-24.8) for ultrasound hypercoiling. The positive likelihood ratio for interventional delivery for non-reassuring fetal status was 1.2 (95% CI 0.2-9.0) for ultrasound hypocoiling, and 10.3 (95% CI 2.1-50.2) for ultrasound hypercoiling. CONCLUSIONS: Strong correlation coefficients comparing the aUCI and pUCI do not reflect agreement. Since the limits of agreement were almost as wide as the full range for the pUCI, the aUCI does not predict the pUCI with sufficient precision. Larger prospective studies are required to confirm the predictive potential of the aUCI for adverse pregnancy outcome.

Adult↗
PubMed2005

The transplacental passage of prednisolone in pregnancies complicated by early-onset HELLP syndrome.

During pregnancy the placental 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2) enzyme inactivates prednisolone by interconversion into prednisone, protecting the fetus from high levels of prednisolone. Recent reports suggest decreased placental 11beta-HSD2 activity in pregnancies complicated by preeclampsia. The purpose of our investigation was to study the transplacental passage of prednisolone in patients suffering from early preterm HELLP syndrome, a severe complication of preeclampsia. We examined the maternal and umbilical cord plasma concentration of prednisolone in nine women receiving 50 mg of prednisolone twice a day. Samples were obtained during caesarean section at a gestational age between 27 and 31 weeks. Mean fetal concentration was 10-fold lower as compared to maternal prednisolone concentration (mean+/-SD 52.8 nmol/L+/-27.0 vs. 477.5 nmol/L+/-300, p<0.01). A significant correlation was found between the last dose of prednisolone to delivery interval and the fetal prednisone concentration (Spearman's correlation coefficient r=-0.946, p<0.000). Our data demonstrate unimpaired placental 11beta-HSD2 activity in patients suffering from HELLP syndrome at early gestational age as shown by both a 10-fold lower fetal prednisolone concentration as compared to the mother and a strong correlation between the last dose of prednisolone to delivery interval and the fetal prednisone concentration. Prednisolone may therefore have less effect on the fetus than betamethasone or dexamethasone.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2005

Corticosteroids, pregnancy, and HELLP syndrome: a review.

Corticosteroids are potent antiinflammatory and immunosuppressive drugs, which are used in the treatment of a wide range of medical disorders. During pregnancy, several corticosteroids are administered for maternal as well as fetal reasons. Prednisone and prednisolone show limited transplacental passage and are thus used for treatment of maternal disease. Dexamethasone and betamethasone, drugs that can easily cross the placenta, are more suitable for fetal indications. During the last decade, administration of corticosteroids was introduced in the treatment of hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome), a severe form of preeclampsia unique to human pregnancy. Several randomized, controlled trials as well as other prospective and retrospective studies have been performed to investigate this beneficial effect of corticosteroids on biochemical measures and clinical signs. This review discusses the characteristics of corticosteroids in humans and details the use of corticosteroids during pregnancy. A review of literature on the effect of corticosteroids on HELLP syndrome is given and possible mechanisms of action are discussed.

Adrenal Cortex Hormones↗
PubMed2004

[Activity loss of Von Willebrand factor cleaving protein (ADAMTS-13) is diagnostic for primary and pregnancy-related thrombotic thrombocytopenic purpura].

OBJECTIVE: To determine whether the measurement of the Von Willebrand factor cleaving protease ADAMTS-13, such as is carried out at the University Medical Centre of Utrecht, The Netherlands, contributes towards the diagnosis and treatment of patients with thrombotic thrombocytopenic purpura (TTP). DESIGN: Descriptive. METHOD: In a group of 98 patients from 21 hospitals, with a Coombs-negative haemolytic anaemia and thrombocytopenia, the ADAMTS-13 activity was measured. Treatment was given irrespective of ADAMTS-13 activity. RESULTS: ADAMTS-13 activity was absent in 27 of 29 patients diagnosed with primary TTP and in all 5 pregnancy-TTP patients. In patients suffering from TTP after bone marrow transplantation (post-BMT) and in all other patients included in this study, ADAMTS-13 activity was normal. Of the 32 patients with absent ADAMTS-13 activity, 28 underwent plasmapheresis. This treatment proved effective as all 28 patients responded well. 17 patients with normal ADAMTS-13 activity also underwent plasmapheresis; 5 (30%) responded well to treatment. In 2 cases a final diagnosis of primary TTP was made, in a further 2, haemolytic uraemic syndrome and in 1 case sepsis was diagnosed. CONCLUSION: In this study, the absence of ADAMTS-13 activity predicted primary TTP and TTP of pregnancy with a sensitivity of 93% and a specificity of 100%. Absence of ADAMTS-13 activity is a strong indication for plasma exchange.

ADAM Proteins↗
PubMed2003

Increased high molecular weight fibrinogen in pre-eclampsia.

INTRODUCTION: The major coagulation protein fibrinogen (Fg) is a heterogeneous protein with three main fractions: high molecular weight fibrinogen (HMW-Fg), low molecular weight fibrinogen (LMW-Fg) and low molecular weight' fibrinogen. The clottability of high molecular weight fibrinogen is highest as compared to the other fractions. Pre-eclampsia is associated with a state of hypercoagulability, and with an increase of fibrinogen concentration. The aim of the present study was to examine if the increased total fibrinogen plasma concentration in patients with pre-eclampsia is associated with a change in distribution of the main fibrinogen fractions. MATERIAL AND METHODS: Plasma was collected from 14 patients with pre-eclampsia and from 14 healthy pregnant matched controls. Total fibrinogen concentrations were determined according to Clauss. The percentage high molecular weight fibrinogen was assessed by SDS-electrophoresis and densitometry after isolation of fibrinogen by precipitation. The study groups were compared by the Mann-Whitney U-test. RESULTS: The median (range) total fibrinogen concentration in the pre-eclampsia group was 5.04 (3.25-6.51) g/l and in the control group 4.19 (3.61-5.38) g/l (p<0.05). The median (range) percentage high molecular weight fibrinogen was 76.5 (69.6-84.0)% and 73.0 (69.0-78.9)% in the pre-eclampsia and control group, respectively (p<0.05). CONCLUSIONS: In pre-eclampsia, the concentration of total fibrinogen is increased and the percentage high molecular weight fibrinogen is also slightly higher than in normal pregnancy. These results may be a reflection of the exaggerated inflammatory response, and subsequent endothelial activation, which are currently believed to be the key pathophysiological mechanisms in pre-eclampsia.

Adult↗
PubMed2003

Changes of plasma lipoprotein(a) during and after normal pregnancy in Caucasians.

OBJECTIVE: Elevated plasma concentrations of lipoprotein(a) are associated with an increased risk for development of atherosclerosis. High lipoprotein(a) concentrations may also be associated with pregnancy-induced hypertension and pre-eclampsia, but reference data on the course of lipoprotein(a) during uneventful pregnancies are limited and questionable. METHODS: We studied plasma lipoprotein(a) concentrations in 19 healthy nulliparous Caucasian women during and after uncomplicated pregnancy. Blood was sampled every 4 weeks during pregnancy from 9 weeks onwards, during labor and at 2-4 weeks and 3-5 months after delivery. An apolipoprotein(a) (apo(a)) isoform-independent enzyme-linked immunosorbent assay (ELISA) was used to measure lipoprotein(a). Multilevel analysis was used to describe the data. RESULTS: Lipoprotein(a) increased until 35 weeks, subsequently decreased slightly until delivery, and fell to values below early pregnancy concentrations thereafter. The curve is defined by the formula lipoprotein(a) (mg/l) = exp [4.789 + (0.05215 x GA) + (-0.0007371 x GA2)] where GA = gestational age in weeks. CONCLUSIONS: We constructed a curve for plasma lipoprotein(a) which may serve as the standard reference for changes in pregnancy. Its formula is helpful in predicting changes of gestational age-dependent changes of lipoprotein(a) in normal pregnancy.

Adult↗
PubMed2002

Placental pathology in early onset pre-eclampsia and intra-uterine growth restriction in women with and without thrombophilia.

OBJECTIVE: The incidence of placental thrombotic lesions in early onset preeclampsia (PE) and/or intrauterine growth restriction (IUGR) were compared between women with and without thrombophilia or hyperhomocysteinemia. STUDY DESIGN: Matched case-control study. 183 women with a history of early onset PE and/or IUGR were tested for thrombophilia and hyperhomocysteinemia. From the 66 women with a thrombophilic factor the placental histological slides were available in 47 women. These were matched for maternal condition (PE and/or IUGR), gestational age at delivery, parity and maternal age, to 47 women with no thrombophilic factor. All slides were revised for lymphohistiocytic villitis, fetal thrombosis and fibrin depositions. RESULTS: There were no significant differences between the placentas of the matched groups with and without a thrombophilic factor. CONCLUSION: Placental thrombotic and inflammatory lesions associated with early onset PE and/or IUGR do not occur more often in women with compared to women without thrombophilia or hyperhomocysteinemia.

Case-Control Studies↗
PubMed2002

The umbilical coiling index in normal pregnancy.

OBJECTIVE: To provide reference values for the umbilical coiling index in uncomplicated pregnancy. METHODS: Umbilical cords were collected from livebom singleton infants born after uncomplicated pregnancies. The umbilical coiling index (UCI) was calculated as the number of coils divided by the cord length in centimeters. The mean value (SD) for the UCI was calculated, and possible correlations of the UCI with maternal age, parity, gestational age at delivery, mode of delivery, sex and birth weight of the infant were examined. RESULTS: A total of 122 umbilical cords were included. The frequency distribution of the UCI was skewed to the right. The mean (SD) UCI was 0.17 (0.009) coils/cm. There were no significant correlations of the UCI with maternal age, parity, gestational age at delivery, mode of delivery, sex or birth weight of the infant. CONCLUSIONS: This is the first study to determine the UCI in a group exclusively consisting of uncomplicated pregnancies. The mean value that we found for the UCI may serve as the standard reference, allowing proper interpretation of umbilical coiling in complicated pregnancy.

Adult↗
PubMed2002

Fetal and maternal cardiovascular diurnal rhythms in pregnancies complicated by pre-eclampsia and intrauterine growth restriction.

OBJECTIVES: To determine whether the diurnal blood pressure profiles in pregnant women with pre-eclampsia and/or intrauterine growth restriction (IUGR) differ from those in normal pregnant controls, and, if so, to establish whether such a difference is accompanied by altered diurnal rhythms of fetal heart rate (FHR) and its variation. METHODS: Twenty-two women in the third trimester of pregnancy with pre-eclampsia, IUGR, or both, entered the study. Eleven healthy pregnant women served as controls. Maternal systolic and diastolic blood pressures and heart rate (MHR) were determined automatically at 30-min intervals during a period of 26 h starting at 09.00. During the study period, nine 1-h recordings of FHR were made at predetermined timepoints. FHR was analyzed numerically. RESULTS: Systolic and diastolic blood pressures and MHR showed diurnal patterns, with the highest values during the day and a trough during the night in all women. Daytime and night-time blood pressures were higher in pre-eclamptic women (p < 0.001), and the day-night difference was smaller than in controls (p < 0.001). Diurnal patterns of FHR and its variation did not differ qualitatively between the three study groups. However, FHR was affected by the maternal blood pressure profile, and all FHR parameters and their diurnal ranges were quantitatively different in IUGR fetuses (p < 0.05). CONCLUSION: In pre-eclamptic women, there was blunting of the diurnal blood pressure profile. This altered maternal hemodynamics was associated with a similar reduction in FHR amplitude during the 26-h period but not with FHR variation. Although diurnal rhythms of FHR and its variation persisted qualitatively in the IUGR fetuses, they seemed to have been reset quantitatively, leading to a flattened diurnal pattern.

Adult↗
PubMed2001

Salivary cortisol levels and anxiety are not increased in women destined to develop preeclampsia.

OBJECTIVE: To compare salivary cortisol levels and maternal anxiety (general and pregnancy-specific) in the early and late second trimester of pregnancy between women who developed preeclampsia (PE) and women who remained normotensive. DESIGN: Nested case-referent study. In a prospectively studied cohort of 250 pregnant women, nine women developed PE in late pregnancy. These nine patients were matched and compared with nine controls. Diurnal cortisol levels were obtained by collecting saliva samples at 17-18 and 27-28 weeks gestation. Salivary cortisol levels were determined by radioimmunoassay. Maternal anxiety was determined by Spielberger's State-Trait Anxiety Inventory (STAI) and a pregnancy-specific stress questionnaire. RESULTS: For both patients and controls, a similar pattern of salivary cortisol excretion was observed. Salivary cortisol levels and anxiety scores (general and pregnancy-specific) did not differ significantly between patients and controls. CONCLUSIONS: Our findings do not lend support to a role for maternal anxiety or second trimester increases in circulating stress hormones in the pathogenesis of PE.

Analysis of Variance↗
PubMed2001

Placental superoxide is increased in pre-eclampsia.

One of the current hypotheses on the pathophysiology of pre-eclampsia (PE) states that the placenta secretes one or more cytotoxic factors resulting in maternal endothelial dysfunction. Among the candidate factors are the products of increased oxidative stress. Although there is circumstantial evidence of such an increase, direct evidence is still lacking. Electron paramagnetic spin trap resonance (EPR), the most direct method to detect free radicals in tissues, was used to measure superoxide levels in placentae from normal pregnancies (n=13) and pregnancies complicated by PE (n=10). The superoxide level was significantly increased in the placental tissue of pre-eclamptic women. Moreover, upon inhibition of Cu-Zn superoxide dismutase (SOD) activity the relative increase of the superoxide levels was significantly smaller in the placentae from the PE patients, implying decreased basal Cu-Zn SOD activity. These findings lend direct support to the hypothesis that oxidative stress in placental tissue is increased in PE.

Adult↗
PubMed2001

The accuracy of lamellar body count and lecithin/sphingomyelin ratio in the prediction of neonatal respiratory distress syndrome: a meta-analysis.

OBJECTIVE: To compare the performance of the lecithin/sphingomyelin ratio and the lamellar body count in the prediction of neonatal respiratory distress syndrome. DESIGN: Meta-analysis. SAMPLE: Six studies reporting on the performance of both the lecithin/sphingomyelin ratio and the lamellar body count published between January 1966 and August 1999. METHODS: We performed a computerised MEDLINE search to identify articles published on the subject. For the six selected studies, prevalence of respiratory distress syndrome and sensitivity and specificity of the tests in the prediction of respiratory distress syndrome were calculated, and overall performance was assessed by constructing summary receiver-operating characteristic curves. RESULTS: The constructed summary receiver-operating characteristic curves showed the lamellar body count to perform slightly better than the lecithin/sphingomyelin ratio in the prediction of respiratory distress syndrome (P= 0.13). CONCLUSIONS: Since the lamellar body count can be performed quickly and since it is less expensive than the lecithin/sphingomyelin ratio, we recommend the former as the test of first choice in the assessment of fetal lung maturity.

Amniotic Fluid↗
PubMed1999

[Sodium intake during pregnancy].

International studies have yielded contradictory results on efficacy of a sodium-restricted diet during pregnancy in preventing and curing hypertension of pregnancy. In the Netherlands three studies have been performed to investigate the value of dietary sodium restriction in pregnancy; they concerned epidemiology, prevention and treatment. Midwives often prescribed this dietary intervention. Urinary sodium excretion was not related to blood pressure changes in pregnancy. Dietary sodium restriction from the third month of pregnancy onwards did not reduce the incidence of pregnancy-induced hypertension. Maternal side effects were a decreased intake of nutrients, decreased maternal weight gain, lowered plasma volume and stimulation of the renin-angiotensin-aldosterone system. A dietary sodium restriction in women with early symptoms of pregnancy-induced hypertension showed no therapeutic effect on blood pressure. There is no place for dietary sodium restriction in the prevention or treatment of hypertension in pregnancy.

Adult↗
PubMed1999

Sodium-blood pressure interrelationship in pregnancy.

In non-pregnant individuals, a strong positive association of sodium intake with blood pressure has been established, but the relationship between sodium intake and blood pressure in human pregnancy remains obscure up to date. The aim of this prospective observational cohort study was to assess the relationship between urinary sodium excretion (as a measure for intake) and blood pressure from the early second trimester onwards throughout pregnancy. The study group consisted of 667 low-risk women with singleton pregnancies, of whom 350 were nulliparous and 317 parous. Blood pressure was measured in a standardised fashion at predetermined intervals from the first antenatal visit prior to 16 weeks gestation until delivery. Urinary sodium excretion was measured in 24-h urine collections on at least four occasions between 16 and 38 weeks gestation. Main outcome measures were the coefficients of correlation between changes in urinary sodium output and changes in blood pressure during six different gestational epochs. No significant correlations were found between changes in urinary sodium output and changes in blood pressure. Correlation coefficients were alike for nulliparous and parous women and for different gestational intervals. Prior to 32 weeks gestation, no differences were observed in sodium excretion between women who remained normotensive and those who developed gestational hypertension. These results suggest that changes in sodium intake are not associated with blood pressure changes in low-risk pregnant women. Blood pressure increases as observed in the second half of normotensive and hypertensive pregnancies are unlikely to be caused by changes in renal sodium handling.

Adult↗