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J Egberts

Publications and source records attributed to J Egberts.

At least 19 recordsLinked to original sources
PubMed2002

Plasma guanosine 3',5'-cyclic monophosphate and severity of peri/intraventricular haemorrhage in the preterm newborn.

UNLABELLED: A poorly controlled cerebral circulation, caused by excessive production of nitric oxide, has been suggested as predisposing to peri/intraventricular haemorrhage (PIVH) in the immature neonate. It is hypothesized that a relation exists between plasma cyclic GMP (cGMP) as an effector of endogenous vasodilatory nitric oxide production and severity of PIVH. In 83 consecutively admitted preterm neonates, nitric oxide production was assessed by measuring plasma cGMP at 0, 24, 48, 72 and 168 h of age. Simultaneously, cranial ultrasound investigations were performed and haemodynamic parameters registered. The investigations showed that 60 neonates (72%) had no PIVH; 18 neonates (22%) had mild to moderate PIVH; and 5 neonates (6%) had severe PIVH. At 48 and 72 h of age, cGMP levels of infants with severe PIVH were significantly higher than those of infants with no or only mild PIVH, whereas at 72 and at 168 h, infants with moderate PIVHs had significantly higher cyclic cGMP levels than infants without PIVH. Finally, at 168 h of age infants with mild PIVH also had higher cyclic cGMP values than those of infants without PIVH. Maximal cGMP values preceded the final extension of PIVH in moderate and severe PIVHs. Blood pressure support was necessary significantly more often in infants with moderate and severe PIVH. A logistic regression model revealed that cGMP was significantly associated with PIVH, irrespective of gestational age, mean arterial pressure or severity of infant respiratory distress syndrome. CONCLUSION: Increased cGMP levels are associated with the development of PIVH. It is suggested that vasodilatory nitric oxide-induced impairment of cerebral autoregulation plays a role here.

Cerebral Hemorrhage↗
PubMed2002

A new method to determine the feto-placental volume based on dilution of fetal haemoglobin and an estimation of plasma fluid loss after intrauterine intravascular transfusion.

OBJECTIVES: (1) To calculate the feto-placental volume (FPV), using the haematocrit (Ht) values and the percentages of fetal haemoglobin (HbF), before and after red blood cell transfusion. (2) To estimate the transfusion-induced loss of plasma fluid. DESIGN: Retrospective analysis of data of 42 anaemic fetuses at the first transfusion [gestational age (GA) 19-36 weeks]. SETTING: Department of Obstetrics, Leiden University Medical Centre, The Netherlands. SAMPLE: Fifteen hydropic and 27 non-hydropic fetuses. METHODS: Donor blood volume (V(donor)) and Ht (Ht(donor)), fetal pre- and post-transfusion Ht values (Ht(initial), Htfinal) and percentages of HbF (HbF(initial) and HbF(final)) were used to calculate the FPV. The total red cell volume after transfusion (RCV(final)) and Ht(final) were used to estimate the plasma fluid loss. MAIN OUTCOME MEASURES: Feto-placental blood volume and loss of plasma fluid. RESULTS: The equations that use Htfinal over-estimate the FPV when the formula does not account for the difference between donor and post-transfusion Ht (FPV(Ht) = 21.36 * GA, - 390; r = 0.89). FPV is underestimated (FPV(Ht) = 9.90 * GA - 172; r = 0.84) when the blood volume increases with a volume less than the added donor blood volume. The calculation of FPV, using HbF percentages and the initial fetal RCV, is independent of volume changes (FPVHbF = 15.10 * GA - 279; r = 0.85). Comparing RCV(final) and Ht(final) values showed that 31.1 +/- 14.5% of the transfused volume was lost. Results of the hydropic fetuses did not differ from those of the non-hydropic fetuses. CONCLUSIONS: FPV values based on Ht values are less reliable than those based on RCV and HbF findings. When, for practical reasons, Ht values have to be used, we propose an adapted equation for the calculation of the necessary volume of donor blood: V(donor) = FPV(HbF) * (Ht(final) - Ht(initial) / (Ht(donor) - 0.70 * Ht(final)).

Blood Transfusion, Intrauterine↗
PubMed2001

Derivated fetal haemoglobin as a marker for red cell age in the human fetus reflecting stimulated or impaired red blood cell production.

We have determined whether derivated fetal haemoglobin (dHbF, consisting of glycated and acetylated HbF) can be used as a cell age marker for fetal red blood cells (RBCs). Cord blood was obtained between 19 and 39 weeks of gestation from 28 alloimmunised anaemic fetuses (23 RhD+ and 5 Kell) and from 20 non-anaemic fetuses and newborns (controls). Density gradient centrifugation was applied to 36 samples (20 RhD+, 15 controls and 1 Kell) to obtain fractions of increasing cell age. Blood samples were used for measurements of mean cellular volume (MCV), mean cell haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), pyruvate kinase activity (PK) and derivated fetal haemoglobin (dHbF) by cation-exchange HPLC. Reticulocytes were counted only in the whole blood samples. In all density gradient separated RBC fractions, the values for MCV, MCH and PK activity decreased and those of MCHC and dHbF increased with increasing density (equivalent to increasing cell age). The mean density was lower for RBCs of the anaemic RHD group (1.072+/-0.007 g/ml) than for the non-anaemic controls (1.077+/-0.005 g/ml) (p<0.05) The RBC density of the Kell sensitised fetus did not differ from those of the controls. In the control group, the values of the cell age markers in whole blood changed significantly with the gestational age, showing an increase of mean age of the erythrocyte population. The best linear relationship was found for dHbF (y=6.28+0.17*weeks; r=0.84; p<0.001). In the anaemic RhD+ fetuses, the RBC age markers did not change with gestational age; the dHbF percentages were lower, and the MCV, MCH, PK values and the reticulocyte counts were higher than in the controls (0.05<p<0.001). The dHbF values of the Kell sensitised fetuses were above (p<0.01) and the reticulocyte counts were below normal (p<0.05) for gestational age. For the anaemic fetuses, a significant number of the dHbF values (86%) and of the reticulocyte counts (78%) differed from the values of the controls (p<0.01). The dHbF percentages in RhD+ fetuses showed the best correlation with the Hb deficit, which is a measure for anaemia (r=-0.81, p<0.0001). We conclude that the percentage derivated HbF may indicate whether the RBC production is normal for gestational age. It may in that sense reflect stimulated or impaired erythropoiesis in alloimmunised haemolytic anaemia.

Anemia, Hemolytic↗
PubMed2001

Nitric oxide production during the early neonatal period in small-for-gestational-age infants.

UNLABELLED: In a study of endogenous nitric oxide production in growth-retarded, very preterm newborns (<32 wk GA), urinary NOx/creatinine ratio and plasma guanosine 3',5'-cyclic monophosphate levels were determined during the early neonatal period. Newborns were divided into three groups: appropriate-for-gestational-age (AGA, n = 19), moderately small-for-gestational-age (SGA, n = 13) and severely SGA (n = 6) infants. Severely SGA infants showed significant higher values of nitric oxide derivatives during the first 24 h of life compared with the other groups. CONCLUSION: An increased NO production is found in SGA infants during the first 24 h after birth. This may reflect an increased intrauterine nitric oxide production in the feto-placental circulation found in cases with intrauterine growth retardation,

Analysis of Variance↗
PubMed2000

Evidence of endothelium involvement in the pathophysiology of hydrops fetalis?

A fetus with signs of hydrops is at high risk of intrauterine death. The pathophysiology of hydrops fetalis is still unclear. We found decreased concentrations of cyclic guanosine monophosphate in fetal plasma of alloimmunized pregnancies complicated by hydrops fetalis, which might suggest reduced nitric oxide production due to injury of fetal vascular endothelial cells.

Adult↗
PubMed2000

Apparent rejuvenation of transfused donor blood in the fetus is due to accelerated removal of the older RBCs.

BACKGROUND: In severely anemic fetuses of women alloimmunized to RBC antigens, transfused donor RBCs disappear faster than in adults. This may result from an accelerated linear or nonlinear decline with time. It was investigated whether changes in donor RBC age characteristics after circulation in the fetus may reflect the main type of cellular decline. STUDY DESIGN AND METHODS: Donor RBC age characteristics (density, mean cell volume [MCV], and mean cell Hb content [MCHC]) were determined before intrauterine transfusions. Density gradient centrifugation was used to obtain RBCs of different ages. The results from gradient centrifugation were used to calculate mean values for the density, MCV, and MCHC to be expected after the transfusion interval, assuming a linear decline in RBCs of 1 percent per day. Donor and fetal RBCs, taken just before the second transfusion, were separated by agglutination with IgM D MoAb. For these donor cells, the observed mean values for density, MCV, and MCHC were compared with the calculated, expected values (n = 12). RESULTS: The mean +/- SD transfusion interval was 17.9 +/- 3.6 days. The Hb declined by 1.75 +/- 0.62 percent per day (n = 9). After the transfusion interval and contrary to the expected changes, cell density and MCHC decreased and MCV increased significantly (0. 001<p<0.02). This difference between actual and calculated values decreased with increasing intervals; for MCV, it was also associated with a greater decline in Hb per day (p<0.05). CONCLUSION: All donor cells age during circulation in the fetus. However, after the transfusion interval, the donor RBC population remaining is apparently younger than the RBC population before transfusion. This results from a preferential disappearance of older donor RBCs and not from a linear loss of cells with time. The removal of older RBCs before the transfusion may increase the time between transfusions and thereby reduce the total number of transfusions required.

Blood Component Removal↗
PubMed1999

Nitric oxide metabolites, cyclic guanosine 3,5 monophosphate and dimethylarginines during and after uncomplicated pregnancies: a longitudinal study.

OBJECTIVE: In cross-sectional studies, the variability between women may mask or deny gestational changes, related to the nitric oxide-cyclic GMP system. Therefore, we analyzed longitudinally as markers of this system, the urinary levels of nitrite+nitrate (NOx), cyclic guanosine 3',5' monophosphate (cGMP) and of the inhibitor of nitric oxide synthase, dimethylarginine (DMA). STUDY DESIGN: Late-afternoon urine samples were obtained from 20 women with uncomplicated pregnancies and nine non-pregnant women. Creatinine concentrations (mol) were determined with the Jaffé reagent and NOx (mmol) with the Griess reagent after reduction of nitrate. cGMP (micromol) was determined in an enzyme immunoassay and DMA (mmol) after solid-phase extraction and liquid chromatography. Trend analyses and (paired) t-tests were done for detection of time-related differences. RESULTS: The NOx/creatinine (mmol/mol) ratios of the non pregnant women (63.8+/-18.8, S.D.) did not differ from those of the pregnant women at the onset of pregnancy (70.5+/-36.4). Over the entire pregnancy period these ratios declined significantly (P<0.001) and lower values were found at the end of gestation and after birth (49.6+/-22.4). The cGMP/creatinine (micromol/mol) and DMA/creatinine ratios (mmol/mol) changed parabolically (P<0.001). The maxima of 68.0+/-19.9 and of 4.95+/-1.01 were found at week 20 and 16, respectively. These ratios declined to 45.2+/-17.7 and to 4.03+/-0.83 at the end of gestation but not further during parturition (39.6+/-17.2 and 4.01+/-1.90). The lowest cGMP/creatinine ratios occurred one month after birth (27.4+/-15.7) while in the non-pregnant women the value was 15.3+/-6.2 microM/M. The lowest DMA/creatinine ratios, measured one month after birth (3.41+/-1.28 mmol/mol) were similar to those of the non-pregnant women (3.75+/-0.39 mmol/mol). Positive instead of negative relationships were found between the DMA results and those of the cGMP (P<0.001) and NOx determinations (P<0.05). CONCLUSIONS: (1) The gestational changes of the urinary NOx/creatinine and especially of the GMP/creatinine ratio reflect most likely changes in vascular resistance. (2) Because of the variability of the results between but also within women, these ratios are useless to monitor supposed changes in NO production during parturition.

Adult↗
PubMed1999

Amniotic fluid nitric oxide metabolites, cyclic guanosine 3',5' monophosphate and dimethylarginine in alloimmunized pregnancies.

OBJECTIVE: To determine the relationship between gestational age or the Liley index (the severity of fetal hemolysis) and the amniotic fluid total nitrite (NOx), cyclic guanosine 3',5 'monophosphate (cGMP) and dimethylarginine (DMA) concentrations. We hypothesized that the concentrations of these components change because of fetal growth or adaptation to fetal anemia. STUDY DESIGN: Amniotic fluids (n=64) were obtained between 23 and 37 weeks from fifty-three patients at risk for alloimmunization. Amniotic fluids from the pregnancies with a Liley index=1 were considered as controls (n=17). Creatinine (C, microMol) was determined with the Jaffé reagent, nitrite (NOx, microMol) with the Griess reagent, cGMP (nMol) by an enzyme immunoassay and DMA (microMol) after HPLC. Multiple regression analysis was used for separating the effects of growth and the estimated degree of anemia. RESULTS: The concentration of NOx, cGMP and DMA was not related to the Liley index or whether or not the fetuses needed blood transfusions. The concentrations of creatinine (C), NOx and cGMP increased during pregnancy (in weeks;W) (C=-69.2+6.28W; r2=0.532; P<0.0001, NOx=-17.6+1.29W; r2=0.106; P=0.01, cGMP=-20.9+1.05W; r2=0.414; P<0.0001). The DMA concentration (3.8+/-0.8(SD) and the NOx/creatinine ratio (181+/-110 mM/M) did not change with gestational age. The cGMP/creatinine ratios (microM/M) increased (cGMP/C=-41.8+4.31W; r2=0.134; P=0.007) whereas the DMA/creatinine ratio (mM/M) declined during pregnancy (DMA/C=73.1-1.34W; r2=0.278; P=0.0002). Consequently, the NOx/DMA and cGMP/DMA ratios increased (NOx/DMA=-6.96+0.43W; r2=0.105; P=0.02, cGMP/DMA=-5.9+0.29W; r2=0.391; P<0.0001). CONCLUSIONS: The concentrations in amniotic fluid of cGMP and NOX, but not of DMA increase during gestation. The cGMP/creatinine ratio increases also whereas that of DMA decreases. The changes in products of the NO-cGMP pathway are independent of mild to moderate fetal hemolysis and may result from fetal growth as well as from reduced inhibition of NO synthase by DMA. Gestational age related effects should be taken into account when analyzing nitric oxide metabolites in amniotic fluids.

Amniocentesis↗
PubMed1998

Cervicovaginal fetal fibronectin concentrations: predictive value of impending birth in postterm pregnancies.

OBJECTIVE: To determine the predictive value of cervicovaginal fetal fibronectin (fFN) concentrations > or =50 ng/ml for spontaneous onset of labour within 3 days in pregnancies of 41 weeks gestation or more. STUDY DESIGN: In the Department of Obstetrics, Leiden University Medical Centre, and of the Diaconessen Hospital, Voorburg (The Netherlands), 126 cervicovaginal secretions of fFN, from 80 consenting women between 287 and 304 days gestation were collected. Pregnant women underwent sterile speculum examinations for cervicovaginal sampling from the 41st week onwards. The fFN concentration in these samples was determined with a quantitative solid-phase enzyme-linked immunosorbent assay. Concentrations of <50 ng fFN per ml were characterised as negative test results, meaning that spontaneous delivery would not take place within 3 days, and those of > or =50 fFN ng/ml were taken as positive test results. Sensitivity and specificity of the fFN test were calculated for predicting spontaneous birth. Parametric and nonparametric tests were used for evaluating differences and correlations. RESULTS: Spontaneous delivery took place after 2.5+/-2.5(SD) days with fFN values > or =50 ng/ml and after 4.7+/-3.6 days with fFN concentrations <50 ng/ml (P<0.001). Sensitivity and specificity of the fFN test predicting spontaneous onset of labour within 3 days, were 0.71 [95% confidence interval (CI) 0.58-0.86] and 0.64 (95% CI 0.48-0.78). If fFN > or =50 ng/ml then a spontaneous onset of labour is more likely to occur within 3 days (odds ratio 4.5 (95% CI 1.8-11.3). CONCLUSIONS: The fFN test does not predict accurately enough whether or not birth will take place within 3 days of sampling. Nevertheless, the higher odds for spontaneous delivery within a few days when the test is positive may be of use in planning adjusted induction of labour.

Cervix Uteri↗
PubMed1997

The disappearance of fetal and donor red blood cells in alloimmunised pregnancies: a reappraisal.

OBJECTIVE: To determine the proportional reduction per day in the number of fetal and donor red blood cells from the fetal circulation after intrauterine intravascular transfusions. DESIGN: A retrospective study of 302 transfusions in 101 fetuses. SETTING: The Department of Obstetrics and Gynaecology of the University Medical Centre Leiden, The Netherlands. METHODS: We measured the haematocrit in fetal samples both before and after repeated intravascular intrauterine transfusion in fetuses with alloimmune disease. The percentage of fetal erythrocytes was determined in Kleihauer-Betke stained smears. The decline of fetal, donor and mixed red blood cells was calculated by dividing the proportional decrease of the haematocrit values of the number of days between transfusions, also after correction for changes in fetoplacental volumes. Results (given as mean [SD]) are derived from the proportional changes of haematocrit per day. RESULTS: The interval between the first and second transfusion (15.5 days [SD 5.2]) was shorter than between subsequent transfusions (means ranging from 21.4 to 21.9 days; P < or = 0.0001). The decline per day of mixed, and of donor red blood cells, calculated without corrections for volume changes did not differ from those corrected for volume changes resulting from the transfusion and from fetal growth (correction factor 1.1 [SD 0.4]). Since the coefficient of variance is smaller for the uncorrected decline values, this type of calculation is preferable for clinical purposes. The disappearance of fetal erythrocytes after the first transfusion (6.1%/day [SD 2.9]) was faster than that of mixed fetal and donor red blood cells (3.2%/day [SD 1.2]; P < 0.0001) and of donor cells alone (1.4%/day [SD 1.6]; P < 0.0001). The decline of the mixed red blood cell population became the same as that of the donor cells (2.2%/day [SD 0.8]) after the second transfusion. This decline of donor cells was higher than after the first transfusion (1.4%/day [SD 1.6]; P < 0.05). After the first transfusion the fetal erythrocytes disappeared faster after transplacental puncture of the umbilical cord (6.6%/day [SD 2.8]) than after transamniotic punctures (5.4%/day [SD 2.7]; P = 0.05). The mixed red blood cell also decreased faster (3.5%/day [SD 1.3] versus 2.8%/day [SD 0.9]; P < 0.01). CONCLUSION: The fast disappearance of fetal erythrocytes, especially after transplacental punctures, shows that the interval between the first and second transfusion needs to be shorter than that for intervals between subsequent transfusions. The number of donor erythrocytes declines by approximately 2% per day.

Anemia↗
PubMed1997

Mortality, severe respiratory distress syndrome, and chronic lung disease of the newborn are reduced more after prophylactic than after therapeutic administration of the surfactant Curosurf.

OBJECTIVE: To test the hypothesis that prophylactic treatment with the surfactant Curosurf (Chiesi Farmaceutici SPA, Parma, Italy) improves survival and respiratory problems more than rescue treatment. DESIGN: Meta-analysis of three prophylaxis versus rescue treatment trials, conducted in four countries. METHODS: A meta-analysis was performed with the original, individual data of mortality, severe respiratory distress syndrome, and chronic lung disease of 671 newborns as outcomes. The random-effects logistic model (accounting for the trial-within-country structure) was applied and adjusted for imbalances in covariates. RESULTS: The probability of each outcome differed between the countries, but the actual treatment effect itself did not. The adjusted odds ratios (ORs) and confidence intervals (CIs) for prophylaxis versus rescue were as follows: mortality: OR, .47; 95% CI, .30 to .73; severe RDS: OR, .50; 95% CI, .33 to .74; and chronic lung disease of the newborn in the survivors at day 28 after birth: OR, .54; 95% CI, .34 to .86. Gender, birth weight, gestational age, and prenatal administration of glucocorticosteroids were significant confounding covariates. CONCLUSION: The analysis shows that for the porcine surfactant Curosurf, prophylactic administration of surfactant has significant advantages over rescue therapy.

Biological Products↗
PubMed1996

Urine samples before dinner are preferable when studying changes in endogenous nitrate production under uncontrolled dietary conditions.

Changes in nitric oxide production result in changes in nitrate excretion, but these are difficult to detect if the daily intake of nitrate varies substantially. Instead of using a sample of the combined urine produced in 24 h for analysis, we studied the urine nitrate concentration in urine discharge at various times of the day. This was done with urine samples from each of seven men after a high dietary nitrate intake, followed by a low dietary intake 24 h later. The lowest variability in nitrate concentration was found in the samples before dinner (late afternoon) (511 +/- 201 (S.D.) mumol/l). However, the pre-dinner samples after a day with a nitrate-rich meal had still a 40% increased nitrate concentration (623 +/- 147 mumol/l), when compared with samples before the high nitrate diet (440 +/- 90 mumol/l; P < 0.05). This effect disappeared on the second day after the high nitrate meal (476 +/- 108 mumol/l). Similar results were found when using the nitrate/creatinine ratio. We conclude that urine samples taken before nitrate rich meals are the most reliable samples for estimating (changes in) endogenous nitrate production.

Adult↗