Publications (6)13.31 Total impact
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Article: Albumin as an adjunct to tracheal occlusion in fetal rats with congenital diaphragmatic hernia: a placebo-controlled study.
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ABSTRACT: We sought to investigate effects of intratracheal albumin injection prior to tracheal occlusion (TO) on lung proliferation in fetal rats with nitrofen-induced congenital diaphragmatic hernia. On embryonic day 19, nitrofen-exposed fetuses underwent TO, TO and 50 microL of either intratracheal albumin 20% or saline, or remained untouched. Main outcome at embryonic day 21.5 was expression of the proliferation marker Ki-67. Secondary outcomes were lung-to-bodyweight ratio (LBWR), tropoelastin expression, density and spatial distribution of elastin, pulmonary/alveolar morphometry, and fetal survival. TO increased Ki-67 messenger RNA and LBWR. Albumin further increased LBWR and density of Ki-67-positive cells but also fetal mortality. TO with or without adjuncts induced elastin deposits at the tips of arising secondary crests, increased air space size, and decreased septal thickness. TO had effects on lung proliferation and advanced the morphologic appearance. Addition of albumin increased density of proliferating cells and LBWR, yet at the expense of additional fetal loss.American journal of obstetrics and gynecology 02/2010; 202(2):198.e1-9. · 3.28 Impact Factor -
Article: The effect of fetal tracheal occlusion on lung tissue mechanics and tissue composition.
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ABSTRACT: Fetal tracheal occlusion (TO) is currently used to treat severe cases of congenital diaphragmatic hernia (DH). Clinical and experimental studies suggest an improved postnatal outcome, but lung tissue mechanics after TO have not been studied. We determined the effect of TO on mechanical impedance and lung tissue components in a rabbit model for DH. At 23 days of gestation (term = 31 days) either a sham thoracotomy or a diaphragmatic defect was induced. DH fetuses were randomly assigned to undergo 5 days later TO. Fetuses were delivered by term cesarean section to determine lung to body weight ratio (LBWR), dynamic lung mechanics and lung impedance. Airway resistance (R(aw)), elastance (H(L)), tissue damping (G(L)) and hysteresivity (G(L)/H(L)) were calculated from impedance data. Collagen I and III and elastin were quantified histologically. LBWR was significantly increased by TO compared to DH (P < 0.001) and resistance and compliance of the respiratory system (R(rs), C(rs)) were improved as well. TO resulted in a significant decrease of R(aw) comparable to observations in sham-fetuses, without effect on lung tissue mechanics H(L), G(L) and hysteresivity. This coincides with a significant decrease of collagen I, III and elastin in comparison to DH fetuses. In this first report on lung tissue mechanics in a rabbit model of DH, TO had a substantial effect on tissue morphology yet this was not mirrored in lung mechanics. We conclude that the effect of TO on lung mechanics without in utero reversal of occlusion, is dominated by airway remodeling.Pediatric Pulmonology 02/2009; 44(2):112-21. · 2.53 Impact Factor -
Article: Effects of maternal retinoic acid administration in a congenital diaphragmatic hernia rabbit model.
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ABSTRACT: Maternal retinoid administration has beneficial effects on lung development in the nitrofen rodent toxic model of congenital diaphragmatic hernia (DH). We wanted to investigate the effects in a surgical model, where the retinoid signaling pathway is not primarily disrupted by the toxic agent. We created DH in fetal rabbits at day 23 of gestation, administrated to the does all trans-retinoic acid (ATRA) or vehicle (VHC) intramuscularly for 8 consecutive days and harvested normal and operated (DH) fetuses at 31 d (n = 7 in each group). Normal lungs exposed to ATRA had increased surfactant protein mRNA levels without change in type II pneumocyte density. There was no measurable effect on lung-to-body weight ratio and airway morphometry by ATRA. In DH lungs (DH/VHC) surfactant protein mRNA levels were increased, as well as the density of type II pneumocytes. When supplemented with ATRA (DH/ATRA) these parameters returned to normal (VHC). Cell proliferation or apoptosis were not influenced by ATRA supplementation. In conclusion, maternal ATRA supplementation does not affect gross anatomic, morphologic or proliferation indices in hypoplastic lungs related to surgically induced DH in rabbit. However, ATRA lowers surfactant protein expression and normalizes type I/II pneumocyte ratio to what is observed in normal lungs.Pediatric Pulmonology 07/2008; 43(6):594-603. · 2.53 Impact Factor -
Article: T2 quantifications of lungs in the fetal lamb with experimentally-induced congenital diaphragmatic hernia.
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ABSTRACT: As an aid to evaluate lung hypoplasia, we investigated the difference between T2 value in fetal lungs of lambs with surgically-induced left-sided diaphragmatic hernia (DH) and gestational age (GA)-matched control littermates (normal [NL]). Lungs were divided into two groups: DH (n = 4) and NL (n = 6). DH was induced at 65-75 days GA (term = 145 days). Fetal MRI was performed (mean GA: 120 days) with half-Fourier acquisition single-shot turbo spin-echo (TE: 60 ms) and rapid acquisition with relaxation enhancement (TE: 350 ms) in the same location (1.5-T Philips, Gyroscan, Best, The Netherlands). T2 of each lung was calculated for multiple regions of interest by taking natural logarithm of signal-to-noise ratio. Mean T2 was compared between DH and NL (unpaired analysis for entire group). Paired comparison between left/right lung was made within DH and NL. Unpaired analysis showed significantly lower T2 of left respectively right lungs in DH (p = 0.02 [respectively] 0.05]) compared to NL (n = 6), as well as between the T2 of all DH versus NL (p = 0.001). In DH, calculated T2 appeared to be lower in left than in right lungs (difference ranged from -2 to +49%). In NL, left and right lungs showed comparable T2. Measurement of T2 signal intensity in DH lungs is feasible and show lower T2 in comparison to NL lungs. Left lungs from lambs with DH show lower T2 than right lungs.Fetal Diagnosis and Therapy 02/2007; 22(2):143-8. · 1.05 Impact Factor -
Article: Fetoscopic surgery: encouraged by clinical experience and boosted by instrument innovation.
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ABSTRACT: Today, modern ultrasound equipment and the wide implementation of screening programmes allow the timely diagnosis of many congenital anomalies. For some of these, fetal surgery may be a life-saving option. In Europe, open fetal surgery became poorly accepted because of its invasiveness and the high incidence of postoperative premature labour and rupture of the fetal membranes. In the 1990s, the merger of fetoscopy and advanced video-endoscopic surgery formed the basis for endoscopic fetal surgery. We review the current applications of fetal surgery via both methods of access. The first clinical fetoscopic surgeries were interventions on the umbilical cord and the placenta, often referred to as obstetrical endoscopy. The outcome of a randomized clinical trial demonstrating that fetoscopic laser coagulation of chorionic plate vessels is the most effective treatment for twin-twin transfusion syndrome (TTTS) has revived interest in endoscopic fetal therapy. Operating on the fetus is another more challenging enterprise. Clinical fetal surgery programmes were virtually non-existent in Europe until minimally invasive fetoscopic surgery made such operations clinically possible as well as maternally acceptable. At present, most experience has been gathered with fetal tracheal occlusion as a therapy for severe congenital diaphragmatic hernia. As in other fields, minimally invasive surgery has pushed back boundaries and now allows safe operations to be performed on the fetal patient. Whereas minimal access seems to solve the problem of preterm labour, all procedures remain invasive, and carry a risk to the mother and a substantial risk of preterm prelabour rupture of the membranes (PPROM). The latter problem may prove to be a bottleneck for further developments, although treatment modalities are currently being evaluated.Seminars in Fetal and Neonatal Medicine 01/2007; 11(6):398-412. · 3.91 Impact Factor -
Article: Tracheal occlusion early in gestation leads to greater lung growth and improved remodeling of pulmonary arteries. A nitrofen rat model for congenital …
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ABSTRACT: Congenital diaphragmatic hernia (CDH) is associated with lung hypoplasia and abnormal pulmonary artery development. Prenatal tracheal occlusion (TO) promotes lung growth and partial reversal of structural anomalies in animal models. Limited data exists regarding TO effects at different phases of lung development. This study evaluates the impact of early (d19, pseudoglandular phase) versus late TO (d20, cannalicular phase) in a nitrofen rat model. Wistar rats were mated within a 1-hour interval. Nitrofen was gavage fed on d9 of gestation. On d19 and d20 fetal TO was performed, respectively. Sham-operated and untouched littermates served as controls. On d21 fetuses were harvested. Only CDH+ fetuses were included in further analyzes with a minimum of 6 fetuses per group. Unpaired t-test with Bonferroni correction was used for statistical analysis. LBWR was significantly increased in both TO groups compared to controls with significantly higher values after early versus late TO. Ki-67 RT-qPCR confirmed significantly increased proliferation in the early TO group compared to late TO and control groups. Media and adventitia thickness (%MT, %AT) were consistently reduced in the early TO group versus controls. Compared to the late TO group %MT was significantly smaller in all, %AT in large pulmonary arteries. Our study confirms enhanced lung growth and reversal of structural abnormalities as a Result of fetal TO in a nitrofen rat model. Effects in this model are more evident after early TO (d19) than late TO (d20). These findings support the concept of early TO for fetal CDH therapy in humans.
