Frans Walther - Academia.edu (original) (raw)

Papers by Frans Walther

European Journal of Pediatrics, 2012

Patent ductus arteriosus (PDA) is a frequent complication in preterm infants. Ibuprofen and indom... more Patent ductus arteriosus (PDA) is a frequent complication in preterm infants. Ibuprofen and indomethacin (both COX inhibitors) are used for pharmacological closure of PDA. In most centers, a failed second course of COX inhibitors is followed by surgical closure. Our aim was to estimate the closure rate of clinically significant PDA after second and third courses of ibuprofen and record possible side effects. A study population, consisting of 164 preterm infants (<32 weeks' gestational age) with PDA admitted at our tertiary care center between November 2005 and September 2011, was retrospectively analyzed. Primary outcome was the closure rate after repeated courses of ibuprofen. The closure rate was similar after the first (109/ 164), second (24/43), and third (6/11) course of ibuprofen (X 2 02.1, p00.350). Late start of the first course of ibuprofen was a predictive factor for increased need of a second course (X 2 04.4, p00.036). No additional side effects of multiple courses of ibuprofen were detected. In conclusion, repeated courses of ibuprofen are an effective and safe alternative for surgical closure and should be considered after failure of the first course of ibuprofen.

Neonatology, 2015

after birth]. The increase in left-to-right shunting during crying was independent from the cardi... more after birth]. The increase in left-to-right shunting during crying was independent from the cardiac cycle as the QRS start of shunt interval time was 138 (82) ms during crying and 156 (35) ms during quiet breathing (n.s.). The DA flow ratio was lower in infants who cried at 0-1 time points versus those who cried at 2-3 time points (n.s.) out of the 3 time points measured. Left ventricular output was higher in infants who cried at 2-3 time points versus 0-1 time points (n.s.). Conclusion: Crying at birth significantly influences the DA shunt during transition.

Biophysical Journal, 2000

Surfactant protein B (SP-B) is a 17-kDa dimeric protein produced by alveolar type II cells. Its m... more Surfactant protein B (SP-B) is a 17-kDa dimeric protein produced by alveolar type II cells. Its main function is to lower the surface tension by inserting lipids into the air/liquid interface of the lung. SP-B's function can be mimicked by a 25-amino acid peptide, SP-B 1-25 , which is based on the N-terminal sequence of SP-B. We synthesized a dimeric version of this peptide, dSP-B 1-25 , and the two peptides were tested for their surface activity. Both SP-B 1-25 and dSP-B 1-25 showed good lipid mixing and adsorption activities. The dimeric peptide showed activity comparable to that of native SP-B in the pressure-driven captive bubble surfactometer. Spread surface films led to stable near-zero minimum surface tensions during cycling while protein free, and films containing SP-B 1-25 lost material from the interface during compression. We propose that dimerization of the peptide is required to create a lipid reservoir attached to the monolayer from which new material can enter the surface film upon expansion of the air/liquid interface. The dimeric state of SP-B can fulfill the same function in vivo.

Neonatology and Blood Transfusion, 2005

In physiological circumstances the foetal immune system matures in an environment which is — exce... more In physiological circumstances the foetal immune system matures in an environment which is — except the foeto-maternal exchange — sterile and devoid from alloantigens. The immune system of the new born is thought to be qualitatively normal, but naïve and memory cells have not yet been established. Indeed, clinical reports show at one hand that the foetus is capable to reject allogeneic haematopoietic stem cells from the 14–16th gestational week onwards [1]. At the other hand the quantitative response is impaired and cord blood transplantation in adults (albeit based on limited numbers) suggest that the capacity to respond in the Graft versus Host (GvHD) direction is reduced. At the level of the B cell, the neonate does not produce immunoglobulins, The neonatal B cells fail to up-regulate co-stimulatory factors, while also a lack of specific T cell helper factors may exist. With respect to the innate immune system, the foetal macrophages are capable of ADC (antigen dependent cytotoxicity) as reflected by alloimmune haemolytic disease, but resistance to microbial infections is impaired. This is attributed to impaired opsonizing capacity of granulocytes and macrophages due to the low levels of immunoglobulins and complement [2].

Biophysical Journal, 2009

been previously shown to simulate the phase properties of the lipid components in lung surfactant... more been previously shown to simulate the phase properties of the lipid components in lung surfactant bilayers and monolayers. Presence of native palmitoylated SP-C reduced the size of lo domains in the DPPC/DOPC/cholesterol membrane model as detected by Förster Resonance Energy Transfer (FRET). Interestingly, very similar effects on the lo/ld equilibrium could be observed in the presence of a recombinant variant of SP-C, in which the two palmitoylcysteines of the native protein had been replaced by phenylalanines. It has been suggested that phenylalanines can act as functional mimics of palmitoylated cysteines in SP-C from some animal species. We therefore propose that the effects of SP-C on domain size could be related to selective interactions of this protein with liquid-ordered membrane regions and that this could be important for SP-C-promoted stabilization of lung surfactant films in vivo.

Journal of Clinical Virology, 2006

Parvovirus B19 is a small single-stranded DNA virus and a potent inhibitor of erythropoiesis, due... more Parvovirus B19 is a small single-stranded DNA virus and a potent inhibitor of erythropoiesis, due to its cytotoxicity to erythroid progenitor cells. Infection with parvovirus B19 during pregnancy can cause several serious complications in the fetus, such as fetal anemia, neurological anomalies, hydrops fetalis, and fetal death. Early diagnosis and treatment of intrauterine parvovirus B19 infection is essential in preventing

Background: Bronchopulmonary dysplasia, a complex chronic lung disease in premature children in w... more Background: Bronchopulmonary dysplasia, a complex chronic lung disease in premature children in which oxidative stress and surfactant deficiency play a crucial role, is characterized by arrested alveolar and vascular development of the immature lung. The spatial and temporal patterns of expression of surfactant proteins are not yet fully established in newborn infants and animal models suffering from BPD.

Vox Sanguinis, 2010

Objective To study the effect of a restrictive guideline for exchange transfusion (ET) on the num... more Objective To study the effect of a restrictive guideline for exchange transfusion (ET) on the number of top-up transfusions in neonates with Rh hemolytic disease.

Vox Sanguinis, 2014

Background Neonates after perinatal asphyxia are at increased risk of thrombocytopenia. The corre... more Background Neonates after perinatal asphyxia are at increased risk of thrombocytopenia. The correlation between perinatal asphyxia and the risk and severity of early-onset thrombocytopenia is not well known.

Transfusion, 2008

The objective was to investigate the use of autologous red blood cells (RBCs) derived from umbili... more The objective was to investigate the use of autologous red blood cells (RBCs) derived from umbilical cord blood (UCB), as an alternative for allogeneic transfusions in premature infants admitted to a tertiary neonatal center. UCB collection was performed at deliveries of less than 32 weeks of gestation and processed into autologous RBC products. Premature infants requiring a RBC transfusion were randomly assigned to an autologous or allogeneic product. The primary endpoint was an at least 50 percent reduction in allogeneic transfusion needs. Fifty-seven percent of the collections harvested enough volume (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =15 mL) for processing. After being processed, autologous products (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =10 mL/kg) were available for 36 percent of the total study population and for 27 percent of the transfused infants and could cover 58 percent (range, 25%-100%) of the transfusion needs within the 21-day product shelf life. Availability of autologous products depended most on the gestational age. Infants born between 24 and 28 weeks had the lowest availability (17%). All products, however, would be useful in view of their high (87%) transfusion needs. Availability was highest (48%) for the infants born between 28 and 30 weeks. For 42 percent of the infants with transfusion needs in this group, autologous products were available. For the infants born between 30 and 32 weeks, autologous products were available for 36 percent of the infants. Transfusion needs in this group were, however, much lower (19%) compared to the other gestational groups. Autologous RBCs derived from UCB could not replace 50 percent of allogeneic transfusions due to the low UCB volumes collected and subsequent low product availability.

Transfusion, 2006

This prospective study investigated whether the odds of receiving a red blood cell (RBC) transfus... more This prospective study investigated whether the odds of receiving a red blood cell (RBC) transfusion in premature infants can be predicted at birth and for whom of these infants harvesting of umbilical cord blood (UCB) for autologous transfusion within 30 days after birth would be worthwhile. Characteristics were evaluated from 288 premature infants with a gestational age between 24 and 36 weeks and who were admitted to our neonatal center. In 144 (63%) of these infants UCB collection was attempted and the early transfusion needs could be compared with the amount of UCB available for transfusion. Sixty-nine of 114 (61%) inborn infants with a gestational age of less than 32 weeks received one or more RBC transfusions of 10 mL per kg within 30 days after birth. Apgar score at 1 minute of less than 6 and gestational age of less than 32 weeks were independently associated with the chance of receiving a transfusion in this group. In 31 of 69 (46%) infants, at least 15 mL of UCB per kg of birth weight was collected and in 28 of 69 (41%) this would have been sufficient to cover their early transfusion needs. The decision to collect UCB for postnatal transfusion can be made just after labor, based on Apgar score and gestational age. The collection of UCB is most effective and efficient for premature infants between 29 and 31 weeks of gestation. For infants less than 29 weeks of gestation, the technical aspects of UCB collection need improvement. This pilot study requires a prospective clinical study to evaluate the proportion of premature infants that can be fully or substantially supported with autologous UCB.

Soft Matter, 2008

Surfactants at air/water interfaces are often subjected to mechanical stresses as the interfaces ... more Surfactants at air/water interfaces are often subjected to mechanical stresses as the interfaces they occupy are reduced in area. The most well characterized forms of stress relaxation in these systems are first order phase transitions from lower density to higher density phases. Here we study stress relaxation in lipid monolayers that occurs once chemical phase transitions have been exhausted. At these highly compressed states, the monolayer undergoes global mechanical relaxations termed collapse. By studying four different types of monolayers, we determine that collapse modes are most closely linked to in-plane rigidity. We characterize the rigidity of the monolayer by analyzing inplane morphology on numerous length scales. More rigid monolayers collapse out-of-plane via a hard elastic mode similar to an elastic membrane, while softer monolayers relax in-plane by shearing. † Electronic supplementary information (ESI) available: Fluorescence microscopy movies showing the different types of monolayer collapse modes. See

Respiratory Research, 2009

Background: Phosphodiesterase-5 inhibition with sildenafil has been used to treat severe pulmonar... more Background: Phosphodiesterase-5 inhibition with sildenafil has been used to treat severe pulmonary hypertension and bronchopulmonary dysplasia (BPD), a chronic lung disease in very preterm infants who were mechanically ventilated for respiratory distress syndrome.

Radiology, 2009

To investigate the incidence and characteristics of cerebellar injury in a cohort of very preterm... more To investigate the incidence and characteristics of cerebellar injury in a cohort of very preterm infants by using the mastoid fontanelle (MF) and posterior fontanelle (PF) approach in addition to routine cranial ultrasonography (US) through the anterior fontanelle (AF), with magnetic resonance (MR) imaging as the reference standard. The institutional review board approved this prospective study and informed consent was obtained. A cohort of 77 preterm infants (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 32 weeks) was examined with serial cranial US throughout the neonatal period by using the AF, PF, and MF views. MR imaging was performed around term-equivalent age in 59 of 77 infants. Sensitivity, specificity, positive predictive value, and negative predictive value of routine cranial US and cranial US with additional views were calculated. At cranial US performed through the MF, seven (9%) of 77 infants were identified to have posterior fossa hemorrhage. In only two of seven infants, the lesions were seen on routine AF views. The PF approach did not increase the detection rate of posterior fossa hemorrhage. MR images confirmed cranial US findings in all cases. MR images showed punctate hemorrhage in the cerebellum in six infants with normal cranial US findings. Among the 59 infants examined with both cranial US and MR imaging, cerebellar injury was diagnosed in 11 (19%). Cerebellar injury is a frequent finding in very preterm infants. Cranial US through the MF can demonstrate injury missed by using the routine AF approach. Punctate hemorrhagic lesions may remain undetected even when the MF approach is used; the prognostic implications of these smaller lesions need further attention.

Pediatric Research, 2014

Cardiac output depends on stroke volume and heart rate (HR). Only HR is used to monitor hemodynam... more Cardiac output depends on stroke volume and heart rate (HR). Only HR is used to monitor hemodynamic transition. In 24 term newborns born via cesarean section, HR and preductal blood pressure (BP) were measured. Also, using echocardiography, left ventricular dimensions and (Doppler derived) left ventricular output (LVO) were examined at 2, 5, and 10 min after birth. Mean (SD) HR and BP did not change with time (mean HR: 157 (21) bpm at 2 min, 154 (17) bpm at 5 min, and 155 (14) bpm at 10 min; mean BP: 51.2 (15.4) mm Hg at 2 min, 50.5 (11.7) mm Hg at 5 min, and 49.6 (9.5) mm Hg at 10 min). Left ventricular end-diastolic diameter increased from 2 to 5 min (14.3 (1.3) vs. 16.3 (1.7) mm; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and stabilized at 10 min (16.7 (1.4) mm). LVO increased between 2 and 5 min (151 (47) vs. 203 (55) ml/kg/min; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and stabilized at 10 min (201 (45) ml/kg/min). LVO increase was associated with rise in left ventricular stroke volume (r = 0.94; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), not with rise in HR (r = 0.37; P value not significant). Left ventricular dimensions and LVO significantly increased the first 5 min after birth and stabilized at 10 min, whereas BP remained stable. LVO and left ventricular dimension increase are presumably due to increasing left ventricular preload resulting from pulmonary blood flow and ductal shunting increase.

Pediatric and Developmental Pathology, 2006

The pathogenetic mechanisms leading to the development of congenital heart disease and congenital... more The pathogenetic mechanisms leading to the development of congenital heart disease and congenital intracranial arteriovenous malformation are still unclear. We report on a monochorionic twin pregnancy with twin-to-twin transfusion syndrome (TTTS), in which vein of Galen malformation (VGM) was diagnosed in the donor twin and transposition of the great arteries (TGA) in the recipient twin. The development of TTTS, VGM, and TGA in a single monochorionic pregnancy could be pure coincidence, but there might also be a causative link. We discuss the possible contribution of genetic factors, fetal flow fluctuations, vascular endothelial growth factors, and the process of twinning itself to the development of these congenital anomalies.

Neuroradiology, 2010

Introduction Cranial ultrasound (cUS) may not be reliable for detection of diffuse white matter (... more Introduction Cranial ultrasound (cUS) may not be reliable for detection of diffuse white matter (WM) injury. Our aim was to assess in very preterm infants the reliability of a classification system for WM injury on sequential cUS throughout the neonatal period, using magnetic resonance imaging (MRI) as reference standard. Methods In 110 very preterm infants (gestational age <32 weeks), serial cUS during admission (median 8, range 4-22) and again around term equivalent age (TEA) and a single MRI around TEA were performed. cUS during admission were assessed for presence of WM changes, and contemporaneous cUS and MRI around TEA additionally for abnormality of lateral ventricles. Sequential cUS (from birth up to TEA) and MRI were classified as normal/ mildly abnormal, moderately abnormal, or severely abnormal, based on a combination of findings of the WM and lateral ventricles. Predictive values of the cUS classification were calculated. Results Sequential cUS were classified as normal/mildly abnormal, moderately abnormal, and severely abnormal in, respectively, 22%, 65%, and 13% of infants and MRI in, respectively, 30%, 52%, and 18%. The positive predictive value of the cUS classification for the MRI classification was high for severely abnormal WM (0.79) but lower for normal/mildly abnormal (0.67) and moderately abnormal (0.64) WM. Conclusion Sequential cUS during the neonatal period detects severely abnormal WM in very preterm infants but is less reliable for mildly and moderately abnormal WM. MRI around TEA seems needed to reliably detect WM injury in very preterm infants.

Neonatology, 2008

Approximately 40 years ago, Dr. Peter Dunn introduced a simple method to determine the insertion ... more Approximately 40 years ago, Dr. Peter Dunn introduced a simple method to determine the insertion length of umbilical catheters in neonates, by using the 'shoulder-umbilical' (S-U) length. Since then, various studies have reported a high rate of malposition of umbilical catheters. One of the possible reasons is that the method used to determine the S-U length varies among paediatric professionals. We performed a questionnaire study among 101 paediatric professionals in the Netherlands and found that the method used by the participants to measure the S-U length was highly inconsistent. Placement of an umbilical venous catheter in a too deep position may lead to potentially life-threatening complications. Therefore, uniformity in measurement is paramount for clinical and teaching purposes. Paediatric professionals using Dunn's definition to place umbilical catheters should adhere more strictly to the original description of the measurement of the S-U length.

Neonatology, 2012

were independently associated with cholestasis: treatment with at least one IUT (OR 5.81, 95% CI ... more were independently associated with cholestasis: treatment with at least one IUT (OR 5.81, 95% CI 1.70-19.80, p = 0.005) and rhesus D type of alloimmunization (OR 4.66, 95% CI 1.05-20.57, p = 0.042). Additional diagnostic tests to investigate possible causes of cholestasis were all negative. In 5 infants (12%), supportive medical and nutritional therapy was started, and one neonate required iron chelation therapy. Conclusion: Cholestasis occurs in 13% of neonates with HDN due to red cell alloimmunization, and it is independently associated with IUT treatment and rhesus D type of alloimmunization.