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J Egberts

Publications and source records attributed to J Egberts.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

Biochemical lung maturity, static respiratory compliance, and pulmonary gas transfer in intubated preterm infants with and without respiratory distress syndrome.

We investigated the relationship between tests of biochemical lung maturity [lecithin/sphingomyelin ratio (L/S ratio)], static compliance of the respiratory system (Crs), and estimates of pulmonary gas transfer [venous admixture and arterial/alveolar (a/A) ratio] in a group of intubated preterm infants with and without respiratory distress syndrome (RDS). Thirty infants were studied once (n = 26) or twice (n = 4). The L/S ratio was obtained by means of high-performance thin-layer chromatography and determination of the phosphorus content. Crs was obtained by the multiple occlusion technique. Transcutaneous blood gases and the percentage of oxygen in the inspired gas were recorded and estimates of pulmonary gas transfer were calculated using algorithms. L/S ratio and Crs correlated well (r = 0.73), indicating a higher compliance in biochemically more mature lungs. Both the a/A ratio and venous admixture correlated significantly with the L/S ratio and Crs (P < 0.001). Crs, L/S ratio, and a/A ratio decreased with increasing severity of radiological RDS, and the percentage venous admixture increased (P < 0.001). Sequential measurements in four infants during the acute phase and after RDS resolved indicated that clinical improvement coincided with improvements in biochemical lung maturity, Crs, and estimates of pulmonary gas transfer.

Chromatography, High Pressure Liquid↗

Theoretical changes in neonatal hospitalisation costs after the introduction of porcine-derived lung surfactant ('Curosurf').

The aims of this study were to determine the effects of porcine-derived lung surfactant (PLS; 'Curosurf') therapy on mortality, periods of care and hospitalisation costs in a model cohort of 1000 premature neonates. In this cohort, 55% of the neonates would develop respiratory distress syndrome (RDS) and this would result in a mortality rate of 35%. The mortality rate among infants without RDS is 19%. Five modes of surfactant therapy were studied: (i) late rescue; (ii) early treatment; (iii) prophylaxis; (iv) multiple-dose treatment; and (v) high multiple-dose treatment. At a 55% incidence of RDS, we found that late rescue and single-dose treatment of severely ill neonates resulted in between 4 and 51 extra survivors, and that multiple-dose treatments increased the number of extra survivors by between 17 and 101. Early treatment and prophylaxis were found to be the most effective strategies, resulting in between 38 and 111 extra survivors. These 2 modes of surfactant therapy were also more effective than the other types of intervention at other incidences of RDS. The introduction of PLS therapy increased the total hospitalisation costs of the cohort of 1000 neonates [71 million Netherlands guilders (NLG) if no patients received surfactant] by 0.8 to 16.0% because of increased survival. Improved survival increased the mean period of intensive care by 0.5 to 12.6% and of nonintensive care by 0.6 to 16.0%, thereby increasing the need for more beds. Costs for PLS ranged from 0.3 to 1.2% of the total hospital costs. The additional costs of PLS therapy per additional survivor, compared with the 'do nothing' option, ranged from NLG68 034 to NLG136 233, and were lowest with prophylaxis and highest with high multiple-dose treatment. Savings in costs per survivor (0.2 to 4.1%) and nonsurvivor (5.1 to 23.1%) were highest with prophylaxis and early treatment, which were found to be the most cost effective of the strategies studied.

Hospitalization↗

Changes of respiratory system mechanics in ventilated lungs of preterm infants with two different schedules of surfactant treatment.

We investigated the time course of changes in the static respiratory system compliance and resistance in relationship to surfactant administration by means of single-breath and multiple-occlusion techniques. The study comprised 12 infants receiving a high-dose schedule (200 mg/kg, maximum 600 mg/kg) and 13 infants receiving a low-dose schedule (100 mg/kg, maximum 300 mg/kg) of porcine surfactant. Eight healthy preterm infants served as a comparison group. Respiratory mechanics were studied before and at 1.5, 8, and 72 h after surfactant administration. Results were related to changes in gas transfer, including an estimate of venous admixture. Static compliance improved after surfactant instillation, and changes were similar in the two treatment groups during the first eight h (0.8 In.(hour + 1) mL.kPa-1). The compliance values remained below the values of the healthy comparison group during the whole study period, but resistance remained at the same level. There was a considerable delay in changes of respiratory mechanics in relationship to the rapid fall of the venous admixture, from 27 to 19%, and the rapid increase of the transcutaneous oxygen pressure/fraction of inspired oxygen ratio from 13 to 27 kPa within the hour. There were no clues that short-term changes in compliance were masked by breathing at a higher and flatter portion of the pressure-volume curve. Both treatment schedules resulted in a similar improvement of compliance within 72 h and the two groups benefited similarly in terms of venous admixture.

Airway Resistance↗

Ultrastructural features of alveolar epithelial cells in the late fetal pulmonary acinus: a comparison between normal and hypoplastic lungs using a rat model of pulmonary hypoplasia and congenital diaphragmatic hernia.

The aim of this study was to describe and compare the ultrastructural features and functional maturity of alveolar epithelial cells in hypoplastic and normal fetal rat lungs. Pulmonary hypoplasia in association with congenital diaphragmatic hernia was induced in fetuses by administration of 2,4-dichlorophenyl-p-nitrophenylether (Nitrofen) to pregnant Sprague Dawley rats (100 mg on day 10 of gestation). Lung tissue of Nitrofen-exposed and control fetal rats aged 19-22 days (vaginal plug day 1, birth day 23) was embedded in Epon. Semithin (1 micron) toluidine blue-stained sections were examined by light microscopy; ultrathin sections (approximately 80 nm) were studied via transmission electron microscopy. In bronchoalveolar lavage fluid from control and Nitrofen-exposed fetuses (day 22), phospholipid fractions and surfactant protein A content were measured semiquantitatively. On day 19 both control and Nitrofen-exposed lungs contained only cuboid alveolar epithelial cells; from day 20 there were cuboid, low cuboid, and thinner epithelial cells. The (low) cuboid cells contained large glycogen fields, some precursory stages of multilamellar bodies (MLBs), and just a few mature MLBs on day 19 and 20; smaller glycogen fields, more precursory stages, and more mature MLBs on day 21; and little or no glycogen but many precursory stages and mature MLBs on day 22. The thinner cells contained little or no glycogen and a few precursory stages of MLBs on days 20-22; very thin cells on day 22 contained neither glycogen nor any precursory stages of MLBs. MLBs and tubular myelin were seen in the lumens of future air spaces from day 20 onward. Nitrofen-exposed lungs differed from control lungs in that inclusion bodies (IBs) were less numerous in (low) cuboid alveolar cells on days 19 and 20, and more glycogen was seen on day 22. In addition intra- and extracellular "MLBs" in exposed lungs more often had an unusual appearance, i.e., a confluent structure and higher electron density. However, despite morphologic differences, there was no clear difference in phospholipid composition and SP-A content per mol phospholipid in bronchoalveolar lavage fluid. We conclude that morphologically hypoplastic lungs are less mature near term, without an apparent effect on surfactant composition.

Animals↗

Comparison of prophylaxis and rescue treatment with Curosurf in neonates less than 30 weeks' gestation: a randomized trial.

OBJECTIVE: The aim of this randomized clinical trial was to evaluate the immediate effects of prophylactic administration of Curosurf and to compare outcomes after prophylactic or expectant management. STUDY DESIGN: Porcine surfactant (Curosurf, 200 mg/kg body weight) was administered intratracheally within 10 minutes of birth to preterm neonates with a gestational age of 26 to 29 weeks (n = 75); rescue-eligible neonates (n = 72) were initially subjected to a sham maneuver. The primary end points of the trial, evaluated at the age of 6 hours, were to obtain (1) a 40% decrease in the ratio between transcutaneous oxygen tension (tcPO2) (kPa) and fraction of inspired oxygen (FIO2), and (2) a 50% decrease in the incidence of radiologically verified respiratory distress syndrome (RDS). After 6 to 24 hours, a similar dose of surfactant was given to the neonates of both the prophylaxis and the rescue-eligible group, if they needed mechanical ventilation with an FIO2 > or = 0.6. RESULTS: At 6 hours the prophylaxis group had, in comparison with the rescue-eligible group, significantly higher tcPO2/FIO2 ratios (mean +/- SD: 39.7 +/- 15.3 vs 28.1 +/- 18.1; P < .001) and less severe RDS by radiological scoring (chi 2 = 14.9; P = .005). Severe RDS was present in 19% of the prophylactically treated neonates versus 32% in the rescue-eligible group (P < .05). The prophylaxis group needed shorter periods of FIO2 > 0.40 than the rescue-eligible neonates (P < .01), and eight neonates of the prophylaxis group (11%) versus 23 of the rescue-eligible group (32%) qualified for rescue treatment with surfactant in the interval 6 to 24 hours (P < .01). There were no differences in the incidence or severity of pneumothorax, pulmonary interstitial emphysema, cerebral hemorrhage, periventricular leukomalacia, patent ductus arteriosus, in the duration of mechanical ventilation or time in supplemental oxygen, or in mortality. CONCLUSIONS: Subgroup analysis revealed (1) that administration of corticosteroids reduced the risk of developing neonatal RDS as effectively as did surfactant prophylaxis at birth, and (2) that prophylaxis was effective especially in neonates with gestational age < 28 weeks or birth weight < 1000 g, in male neonates, and in neonates who had received no antenatal treatment with corticosteroids. Our data indicate that prophylactic treatment with surfactant should be considered in high-risk neonates fulfilling these latter criteria.

Biological Products↗

[Prevention and treatment of respiratory distress syndrome in premature infants using intratracheally administered surfactants].

OBJECTIVE: To study the effects of administration of surfactant immediately after birth (prophylactic) or after 6 hr (therapeutic) to 81 Dutch preterm infants from a multicentre trial. SETTING: University Hospital Leiden and Sint Joseph Hospital, Veldhoven. DESIGN: A randomized controlled trial with stratification for biochemical lung (im)maturity. The aims of the study were (I): to improve the TcPO2/FiO2 ratio by 40% and (2) to prevent the respiratory distress syndrome by 50% at 6 hours after birth. The secondary goal was to compare effects of prophylactic versus therapeutic use of exogenous surfactant (from 6 hours onwards) in surfactant-deficient infants. PATIENTS: The entrance criteria of the study were: (I) inborn children with a gestational age between 26 and 30 weeks, (2) elective intubation and (3) sampling of bronchotracheal or gastric aspirate. After randomization the children received surfactant within 10 minutes after birth prophylactically (n = 42) or 6 hours after birth if they needed more than 60% oxygen (13 of 39 control infants). A second dose of surfactant was given if, at 6 hours after the first dose, the FiO2 was still high (> or = 0.6). TREATMENT: We used a natural porcine surfactant preparation (Curosurf) in a dose of 200 mg/kg given through the endotracheal tube. RESULTS: The mean gestational age of the 81 infants was 28.2 weeks. The TcPO2/FiO2 ratios increased in the prophylactic group compared with the controls (38 versus 30 kPa; p < 0.05). RDS occurred less often and less severely in the prophylactic group (p < 0.05). Neonatal mortality was lower in the prophylactically treated infants (3/42) than in the control group (10/39; p < 0.05). Compared with the control infants with immature lungs, the immature prophylactically treated infants had six hours after birth higher TcPO2/FiO2 ratios (35 vs 13 kPa; p < 0.001), a 35% reduction of the incidence of RDS with a significant reduction of its severity (p < 0.05), and significantly lower mean airway pressures (0.87 versus 1.24 kPa; p < 0.005). The surfactant given 6 hours after birth to the immature controls resulted in an immediate improvement of the oxygenation. Nevertheless, these infants spent more time on the respirator and needed extra oxygen for longer periods than the immature infants prophylactically treated (p < 0.05). CONCLUSION: Surfactant, given either prophylactically or therapeutically, results in clinical improvement of children with biochemically immature lungs. A prophylactic treatment, moreover, results in reduced incidence and severity of RDS, in a significant shortening of the time spent on the respirator and in reduced need of extra oxygen compared with therapeutic treatment. We recommend to give surfactant prophylactically or at the first signs of RDS.

Gestational Age↗

Derivation of tumorigenic and non-tumorigenic mouse alveolar type-II cell lines from fetal type-II cells after a combined in vivo/in vitro carcinogen treatment.

Alveolar type-II cells were isolated from the lungs of fetuses (day 18 of gestation) of the A/WySnAf (A/Sn) mouse strain, which were treated in utero at day 15 with the directly-acting carcinogen N-ethyl-N-nitrosourea (ENU). The isolated type-II cells were again treated with ENU during their initial growth in vitro. After a prolonged culture period, 5 cell lines were obtained, which were identified as type-II cell lines. Differences between cell lines were found with respect to contact-inhibited growth, cell doubling time and ability to grow in a serum-free medium. Two out of the 5 cell lines produced highly invasive type-II cell carcinomas after s.c. injection of 5 x 10(6) cells into nude mice. Thus, both tumorigenic and non-tumorigenic mouse alveolar type-II cell lines were derived after this combined in vivo and in vitro carcinogen treatment of fetal mouse alveolar type-II cells. This offers the possibility of studying in vitro the factors thought to influence lung tumorigenesis in vivo. In addition, our findings strongly suggest that alveolar type-II cells are the progenitor cells of malignant mouse lung tumors.

Animals↗

Estimated costs of different treatments of the respiratory distress syndrome in a large cohort of preterm infants of less than 30 weeks of gestation.

Within a model cohort of 1,000 preterm infants of less than 30 weeks of gestation, the incidence and mortality of RDS change if corticosteroids are used prenatally and surfactant prophylactically or therapeutically after birth. Combined pre- and postnatal therapies give the best results: approximately 125 extra survivors. Therapeutic surfactant administration even in combination with prenatal corticosteroids has cost implications because extra intensive care beds (7-11%) are needed. More special care places (12-24%) are required after each type of intervention. The estimated costs per extra survivor are the lowest for prenatal corticosteroid administration. The combination of corticosteroids prenatally and prophylactic surfactant postnatally seems to be most cost-effective because it produces the greatest number of survivors and the lowest number of intensive and high dependency care days in hospital.

Adrenal Cortex Hormones↗

Development of a human lung surfactant, derived from extracted amniotic fluid.

Using a surfactant preparation of human origin for the treatment of the respiratory distress syndrome (RDS) instead of an animal-derived surfactant will minimize immunological problems. Therefore we isolated surfactant material from human amniotic fluid. Protein and phospholipid fractions of extracted human amniotic fluid (HAFS) were separated by Lipidex 5000 or acidulated LH20 liquid chromatography systems. Fractions of HAFS, the phospholipid or the recombined phospholipid-protein fractions, were tested in the 27-day fetal rabbit model. The results were compared with the results of the corresponding fractions of extracted ovine lung lavage (EOS) and of the already clinically tested surfactant Curosurf. The in situ surface activity of HAFS, EOS, and of their combined phospholipid + protein fractions (200 mg/kg body wt.) resulted in a lung compliance which was significantly higher than the control (saline) values. The compliances of HAFS, EOS, their combined fractions, and Curosurf were similar, but the lung stability values (V5) differed significantly among these surfactant extracts. The best V5 values (greater than or equal to 0.020 ml/g body wt.) were found after installing EOS or its LH20 phospholipid + protein fractions. HAFS had a poor stabilizing capacity which increased significantly after Lipidex chromatography and even more after enrichment of the Lipidex material with 10% palmitic acid. The Lipidex HAFS + 10% palmitic acid surfactant is at present the best obtainable human surfactant extract. Further development is in progress for the clinical application of this surfactant in preterm neonates.

Amniotic Fluid↗

Postmortem effects on the yield and composition of alveolar surfactant from rat lungs.

Isolation of alveolar surfactant from human cadaver lungs might be ineffective because of postmortem effects. We studied therefore in the rat the effect of autolysis on the yield and composition of alveolar surfactant at different intervals after death. The total amount of phospholipids in the lavage fluids decreased at 4 h postmortem and increased thereafter again. Increased amounts of proteins, significant deviations from the normal phospholipid composition of surfactant and decreased surface activity were already present from 2 h onwards. However, a normal alveolar surfactant can be obtained up to 16 h after death by using a sucrose gradient centrifugation procedure. With this procedure it is possible to isolate a surfactant with adequate surface activity from mildly, but not from severely autolytic rat lungs.

Animals↗