Biomedical subjects

Enrico Danzer

Publications and source records attributed to Enrico Danzer.

13 recordsLinked to original sources

PubMed2006

Fetal head biometry assessed by fetal magnetic resonance imaging following in utero myelomeningocele repair.

OBJECTIVE: To examine the impact of fetal myelomeningocele (MMC) repair on fetal head biometry and cerebrospinal fluid (CSF) spaces assessed by magnetic resonance imaging (MR) studies. STUDY DESIGN: Axial measurements of intracranial structures were taken at defined anatomical landmarks. Pre- and postnatal head biometry data and CSF spaces obtained from in utero repaired MMC fetuses (n = 22) were compared to the pre- and postnatal measurements of MMC patients that underwent standard neurosurgical MMC repair after birth (n = 16) and a cohort of age-matched control patients (prenatal, n = 52; postnatal, n = 9). RESULTS: In fetuses with MMC, initial MR scans showed an almost complete absence of supratentorial and posterior fossa CSF spaces. No differences in postnatal CSF spaces were found between controls and prenatally repaired MMC newborns. In fetuses with postnatal MMC repair, CSF spaces remained significantly reduced (p < 0.0001). The mean ventricular diameter (VD) increase in the postnatal repaired MMC group was significantly higher compared to the mean percentage of VD increase in the fetal repaired MMC group (6.4 vs. 4.2 mm; p = 0.02). Pre- and postnatal brain thickness measurements were significantly reduced in both MMC populations compared to age-matched normal values (p < 0.0001). In contrast to postnatally repaired patients, in utero repair fetuses showed significant reversal of hindbrain herniation and normalization of the posterior fossa CSF spaces. CONCLUSION: Mid-gestational repair of MMC promotes normalization of extra-axial CSF spaces. Due to progressive ventriculomegaly, brain thickness remains decreased in both prenatal repaired and age-matched non-repaired MMC patients when compared to age-matched normal values. Restoration of CSF volume in the posterior fossa after in utero repair is indicative of reversal of hindbrain herniation.

Brain↗

PubMed2006

Structural and functional characterization of bladder smooth muscle in fetal rats with retinoic acid-induced myelomeningocele.

Myelomeningocele (MMC) is the most common cause of neurogenic bladder dysfunction (NBD). We recently developed a novel retinoic acid (RA)-induced MMC model in fetal rats. The objective of this study was to use this model to assess functional and structural characteristics of the detrusor muscle in MMC-associated NBD. Time-dated pregnant Sprague-Dawley rats were gavage fed 60 mg/kg RA dissolved in olive oil or olive oil alone [embryonic day 10 (E10)]. Bladder specimens from olive oil-exposed fetuses (OIL; n = 71), MMC (n = 79), and RA-exposed-no MMC (RA, n = 62) were randomly assigned for functional and histopathological evaluation and protein analysis. Contractility responses to field and agonist-mediated stimulation (KCl and bethanecol) were analyzed. The expression patterns of alpha-smooth muscle actin, myosin, desmin, vimentin, and collagen III and I were analyzed by immunohistochemistry and Western blotting. Spatial and temporal distribution of nerve fibers within the detrusor muscle was monitored by neurotubulin-beta-III throughout gestation. Neither OIL, MMC, nor RA detrusor responded to field stimulation. MMC bladder strips showed a significant decrease in contractility after KCl and bethanechol stimulation compared with OIL and RA bladders. Bladder detrusor morphology and expression patterns of smooth muscle markers were similar between groups. Detrusor muscles in OIL and RA fetuses were densely innervated, possessing abundant intramural ganglia and nerve trunks that branch to supply smooth muscle bundles. In MMC bladders, neurotubulin-beta-III-positive nerve fibers were markedly decreased with advancing gestational age and were almost completely absent at term (E22). We conclude that the biomechanical properties of fetal rat MMC bladders are analogous to that seen in humans with MMC-associated NBD. Decreased nerve density indicates loss of peripheral neural innervation throughout gestation. The early observation of decreased innervation and decreased contractility in the absence of morphologic abnormalities in muscle structure or extracellular matrix supports a pathophysiological hypothesis that denervation is the primary insult preceding the observed alterations in bladder muscle structure and function.

Animals↗

PubMed2006

Prenatal glucocorticoids improve lung morphology and partially restores surfactant mRNA expression in lambs with diaphragmatic hernia undergoing fetal tracheal occlusion.

In fetal sheep with surgically created diaphragmatic hernia (DH), tracheal occlusion (TO) can restore lung growth but does not ameliorate the increase in inter-alveolar wall thickness (T(W)). We determined whether prenatal exposure to glucocorticoids (GC) could reduce T(w) in fetuses with DH undergoing TO. At 65 days of gestation, DH was created in 12 fetal sheep, and TO subsequently performed at 110 days (DH/TO). Six of these fetuses were exposed to betamethasone (DH/TO + GC; 0.5 mg/kg; maternal, IM) 48 hr before delivery; Sham operated fetuses (n = 7) served as controls. At 139 days, we measured alveolar surface density (S(V)), parenchymal tissue fraction, T(W), alveolar type 2 (AE2) cell density and lung surfactant protein (SP) mRNA expression. Prenatal GC decreased T(W) and S(V) by 33% and 27% respectively, and increased fixed lung volume (by 55%), AE2 cell density and partially restored SPmRNA expression. Our data indicate that prenatal exposure to GC can reverse some of the negative effects of prolonged fetal TO. We hypothesize that a GC-induced reduction in lung liquid volume during TO contributes, in part, to the observed increase in AE2 cell density and SPmRNA expression.

Animals↗

PubMed2006

Tracheal occlusion in fetal rats alters expression of mesenchymal nuclear transcription factors without affecting surfactant protein expression.

BACKGROUND/PURPOSE: Mesenchymal nuclear transcription factors (MNTF) are involved in lung development and maturation and regulate surfactant protein (SP) expression. Prolonged (>2 weeks) fetal tracheal occlusion (TO) has been shown to accelerate lung growth and inhibit pulmonary surfactant synthesis. The effects of TO on SP expression and MNTF, however, have not been formally assessed. The objectives of this study were to evaluate the effects of short-term (3 days) TO on normal lung growth and protein expression of pulmonary MNTF involved in SP synthesis. METHODS: At E19 (term, 22 days), 2 fetuses per time-dated Sprague-Dawley rats underwent either TO (n = 23) or a sham (n = 22) operation. Lungs were harvested 72 hours post surgery. Pulmonary SP-A; SP-B; SP-C messenger RNA (mRNA) expression; and SP-A and SP-B, Hoxb5, thyroid transcription factor 1, and retinoic X receptor-alpha protein expression were analyzed. RESULTS: Lung weight was significantly increased by TO (TO 0.32 +/- 0.02g vs SHAM 0.14 +/- 0.01 g; P < .001), resulting in 123% increase of the lung-to-body-weight ratio. No difference of SP-A-mRNA (177 +/- 4.3 TO vs 169 +/- 4.4 SHAM; P = .25), SP-B-mRNA (87.7 +/- 0.2 TO vs 87.4 +/- 0.02 SHAM; P = .33), and SP-C-mRNA (186.5 +/- 3.2 TO vs 183.2 +/- 2.7 SHAM; P = .45) expression was found. Surfactant protein A (175.6 +/- 25.3 TO vs 192.5 +/- 19.8 SHAM; P = .59) and SP-B (163.4 +/- 5.2 TO vs 166.8 +/- 9.3 SHAM; P = .75) protein expression were similar in both groups; however, Hoxb5 (70.3 +/- 18.9 TO vs 130.6 +/- 5.1 SHAM; P = .02) and thyroid transcription factor 1 (102.6 +/- 19 TO vs 181.1 +/- 6.3 SHAM; P = .007) expression were significantly decreased. Retinoic X receptor-alpha expression tended to be increased by TO (171.9 +/- 6.0 TO vs 155.4 +/- 6.7 SHAM; P = .06). CONCLUSIONS: Short-term TO late in gestation induces rapid lung growth. Surfactant protein-mRNA and protein expression are not significantly altered. Thyroid transcription factor 1 and Hoxb5 are down-regulated by TO, suggesting that duration and timing of occlusion are important in balancing the effects of TO on lung growth vs lung maturation.

Animals↗

PubMed2006

Prenatal glucocorticoids and exogenous surfactant therapy improve respiratory function in lambs with severe diaphragmatic hernia following fetal tracheal occlusion.

Fetal tracheal occlusion (TO) accelerates lung growth and can reverse severe lung hypoplasia associated with diaphragmatic hernia (DH), however, lung compliance (Cl) and respiratory gas exchange remain abnormal. We determined the individual and combined effects of prenatal glucocorticoids (GC) and exogenous surfactant therapy (S) on postnatal pulmonary function in lambs with DH that underwent prolonged TO. DH was created in 22 fetal sheep at 65 d of gestation and TO performed at 110 d. Eleven DH/TO animals received prenatal GC (betamethasone, 0.5 mg/kg) 48 h before delivery; six GC-treated and five non-GC lambs were administered surfactant (Infasurf, 3 mg/kg) at birth. Six sham-operated lambs served as controls. Lambs were delivered at 139 d gestation and ventilated for 2 h. GC or surfactant therapy alone significantly improved respiratory gas exchange, Cl, and ventilatory efficiency index. Total lung capacity was normalized only in DH/TO lambs that received both GC and S.

Animals↗

PubMed2006

Diagnosis and characterization of fetal sacrococcygeal teratoma with prenatal MRI.

OBJECTIVE: The purpose of this study was to determine whether prenatal MRI provides additional information about fetal sacrococcygeal teratoma compared with prenatal sonography. MATERIALS AND METHODS: Twenty-two pregnant women with fetal sacrococcygeal teratoma underwent prenatal MRI (mean gestational age, 23 weeks). The size, location, mass characteristics, and compressive effects of the tumors were determined and correlated with sonography and postnatal findings. RESULTS: Based on the MRI findings, the following American Academy of Pediatrics, Surgical Section classifications were assigned: type I in six patients, type II in 12, and type III in four. No type IV tumors were found. The sacrococcygeal teratoma appeared entirely cystic in five fetuses, microcystic in one, mixed cystic and solid in 12, and solid in four. The diagnosis of sacrococcygeal teratoma was accurate in all cases assessed at our center using both MRI and sonography. Two additional patients initially referred with the diagnosis of sacrococcygeal teratoma had a different diagnosis at reevaluation at our institution (healthy, n = 1; myelomeningocele, n = 1). MRI was superior to sonography for detecting displacement of the colon (n = 11), urinary tract dilatation (n = 9), hip dislocation (n = 4), intraspinal extension (n = 2), and vaginal dilation (n = 1). In fetuses with sacrococcygeal teratoma types II and III, MRI better showed the cephalic extent of the tumor compared with sonography. MRI findings were confirmed at surgery or autopsy in all patients. Three fetuses with high output cardiac physiology underwent open fetal resection of the tumor at 21-, 24-, and 26-weeks' gestational age with two surviving. CONCLUSION: Our results show that ultrafast fetal MRI is a useful adjunct to the prenatal evaluation of fetal sacrococcygeal teratoma. Compared with sonography, MRI more accurately characterized the intrapelvic and abdominal extent of the tumors and provided more information on compression of adjacent organs. The additional anatomic resolution provided by MRI resulted in more accurate prenatal counseling and improved preoperative planning for surgical resection.

Female↗

PubMed2005

Surfactant protein expression is increased in the ipsilateral but not contralateral lungs of fetal sheep with left-sided diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) impairs fetal lung growth and increases the density of alveolar epithelial type 2 (AE2) cells. There is controversy whether surfactant protein (SP) expression is altered in CDH. The primary aim of this study was to assess SP expression (mRNA and protein) in the left and right lungs of fetal sheep with and without a diaphragmatic hernia (DH). Left-sided DH was created in four fetal sheep at 65 days of gestational age (g.a.). Sham-operated animals were used as controls. At 138 days g.a., lungs were harvested and the following parameters were measured: SP-A, -B, and -C mRNA expression (Northern blot), SP-A and -B expression (Western blot), and AE2 cell density (immunohistochemistry). The lung weight-to-body weight ratio was reduced by 42% in DH animals. The left-to-right lung weight ratio was lower in DH animals (0.47 +/- 0.03 vs. 0.69 +/- 0.03), indicative of asymmetric lung growth. SP-A, -B, and -C mRNA expression were increased by 61.7%, 32.9%, and 75.5%, respectively, in the left lungs of DH animals. SP-A and SP-B were also increased in DH. In the right lung, SP expression (mRNA and protein) was not different between groups. AE2 cell density was higher (by 67%) in the left but not right lungs of DH animals. Although DH in fetal sheep results in significant lung hypoplasia, SP expression is not reduced. On the contrary, SP expression was increased in the ipsilateral lung of fetuses with left-sided DH. Furthermore, AE2 cell density is increased in DH, suggesting that the increase in SP mRNA and protein levels is due to increases AE2 cell number. Our data further support the premise that fetal lung hypoplasia favors an AE2 phenotype.

Animals↗

PubMed2005

Reconstitution of hematopoiesis following intrauterine transplantation of stem cells.

In utero hematopoietic stem cell transplantation is an entirely nonmyeloablative approach to achieve mixed hematopoietic chimerism and associated donor-specific tolerance. This chapter provides the rationale and methodologic detail for the administration of stem cells to the "preimmune" mouse fetus by a variety of routes. The development of murine model systems for in utero transplantation has accelerated progress in the field of in utero hematopoietic stem cell transplantation. Creative use of these models should also have experimental application to the fields of fetal gene therapy, stem cell biology, and developmental biology.

Animals↗

PubMed2003

Minimal access fetal surgery.

The development of fetal surgery has led to promising therapeutic options for a number of congenital malformations. However, preterm labor (PTL) and premature rupture of membranes continue to be ubiquitous risks for both mother and fetus. To reduce maternal morbidity and the risk of prematurity, minimal access surgical techniques were developed and are increasingly employed. Congenital diaphragmatic hernia (CDH), obstructive uropathy, twin-to-twin transfusion syndrome (TTTS), and sacrococcygeal teratoma have already been successfully treated using minimal access fetal surgical procedures. Other life-threatening diseases as well as severely disabling but not life-threatening conditions are potentially amenable to treatment. The wider application of minimal access fetal surgery depends on a continued improvement in technology and a better understanding of complications associated with fetal intervention.

Congenital Abnormalities↗

PubMed2003

Comparison of drainage techniques for biliary atresia.

PURPOSE: Traditional Kasai portoenterostomy and porto-appendiceal duodenostomy have been utilized for biliary atresia. Differences in outcome between patients who underwent either Kasai portoenterostomy or porto-appendiceal duodenostomy were compared. METHODS: A review of all children who underwent a drainage procedure for biliary atresia from 1986 to 2000 (n = 30) was performed. Age at drainage procedure, subsequent liver transplantation, and outcomes were evaluated. Outcome variables included success rates (total bilirubin < 2.0 mg/dL) and survival rate. Statistical analysis was done with chi2 and Student's t test. RESULTS: Long-term follow-up was available on 28 of 30 patients. Age at biliary drainage was insignificant. Success rates between porto-appendiceal duodenostomy (31%) and Kasai portoenterostomy (82%) were statistically significant. Survival rate for patients who underwent a Kasai portoenterostomy was 10 of 11 patients. Survival rate for patients who underwent porto-appendiceal duodenostomy was 14 of 16 patients. Overall survival rate was comparable between porto-appendiceal duodenostomy (88%) and Kasai portoenterostomy (91%). CONCLUSIONS: Although overall survival rate was comparable, patients who underwent porto-appendiceal duodenostomy were less successful in alleviating hyperbilirubinemia compared with Kasai portoenterostomy. This is shown further by the greater incidence of subsequent liver transplantation in infants with prior porto-appendiceal duodenostomy. Although the appendix may serve as an alternative biliary conduit, traditional Kasai portoenterostomy appears to achieve better biliary drainage.

Adolescent↗

PubMed2003

Attitudes of Swiss mothers toward unrelated umbilical cord blood banking 6 months after donation.

BACKGROUND: During the past decade, the use of umbilical cord blood (CB) as a source of transplantable hematopoietic stem cells has been increasing. Little is known about the psychosocial consequences that later affect parents after unrelated CB donation. The objective of this study was to evaluate the attitudes of mothers toward unrelated donation of umbilical CB for transplantation 6 months after giving birth. STUDY DESIGN AND METHODS: A prospective study was performed with a standardized, anonymous questionnaire distributed to 131 women 6 months after CB donation. The questionnaire included topics concerning views about the ethical accuracy of having donated CB, emotional responses after donation, concerns about genetic testing and research with CB samples, attitude toward anonymity between her child and possible unrelated CB recipient, and willingness to repeatedly donate umbilical CB in a next pregnancy. RESULTS: The vast majority (96.1%) stated that they would donate umbilical CB again, and all respondents were certain that their decision to have donated umbilical CB was ethical. With regard to the potential risks of genetic testing and "experimentation" of umbilical CB, a significant correlation (p = 0.01) was found between negative attitudes and the decision not to donate umbilical CB again. Additionally, it was observed that women who had a negative experience concerning the donation of CB would not donate again (p = 0.004). CONCLUSIONS: This study shows a high degree of satisfaction of unrelated umbilical CB donation for banking in women 6 months after delivery. Despite a well-performed and detailed informed consent procedure, one of the ongoing issues for the donators in CB banking involves the concern regarding of improper use of the cells, such as genetic testing or experimentation. Accurate and detailed counseling of pregnant women and their partners therefore maximizes the likelihood that they will donate CB for unrelated banking. These data provide a basis for the improvement of donor selection procedures and public education regarding the use of CB for banking and transplantation.

Adult↗

PubMed2003

The impact of intrapartum factors on umbilical cord blood stem cell banking.

AIMS: Umbilical cord blood can be used as an alternative source for related and unrelated allogeneic stem cell transplantation. This study was undertaken to determine whether intrapartum factors have an influence on the hematopoietic cell compartment of cord blood. METHODS: Cord blood samples were obtained from 102 normal full-term deliveries for the banking of stem cells. We analyzed the influence of intrapartum factors on the count of CD34+ cells, total nucleated cells, colony forming units and total volume of collection. Fluorescence-activated cell sorting was used to measure CD34+ cell numbers. Statistical analysis was undertaken using Pearson correlation test and multiple regression analysis. RESULTS: The higher the infants' birthweight the larger was the volume. A lower arterial umbilical pH and a larger blood volume resulted in an increased number of CD34+ cells. A large blood volume, long duration of labor, lower arterial and venous pH were correlated with more nucleated cells. A higher birthweight, larger blood volume and lower arterial pH resulted in an increased number of colony forming units. CONCLUSIONS: Some intrapartum factors have an impact on the characteristics of collected cord blood cells. Stress during delivery may influence the number of hematopoetic cells, through altered cytokine production. This knowledge may facilitate the selection of optimal cord blood samples for unrelated banking and the early discarding of suboptimal cord blood samples thus resulting in the saving of costs related to expensive further processing.

Antigens, CD34↗

PubMed2002

Ultrasound-guided stem cell sampling from the early ovine fetus for prenatal ex vivo gene therapy.

OBJECTIVE: Prenatal ex vivo gene therapy might be an effective and safe strategy with which to treat severe genetic disorders in utero. For this purpose, autologous fetal stem cells must be collected before the second trimester, transfected in vitro, and transplanted back to the fetus. The aim of this study was to determine whether stem cells can be sampled from the first trimester fetal liver in ongoing gestation. STUDY DESIGN: Fetal liver stem cell sampling was performed in 21 ovine fetuses. Pregnant ewes at 57 +/- 2 gestational days were generally anesthesized. A 20-gauge needle was inserted transcutaneously into the fetal liver under ultrasound guidance. Fetal liver cells were sampled by suction. The numbers of nucleated cells and progenitor/stem cells were determined. RESULTS: All 21 fetuses showed normal heart rate 5 minutes after the procedure. A mean (+/-SEM) of 2.07 +/- 0.5 x 10(7) nucleated cells and 172 +/- 53 colony-forming units per 10(5) cells (hematopoietic progenitors/stem cells) were collected. Fetal loss rate at term was 7 of 21 fetuses (33%). CONCLUSION: This study shows that fetal liver cells can be collected in the early fetus with an ultrasound-guided technique. The number of fetal liver cells that are collectable is large enough for autologous transplantation and engraftment of genetically engineered (transfected) stem cells.

Animals↗