Publications by authors named "Mario Rüdiger"

86 Publications

Mesenchymal stromal cells in the development and therapy of bronchopulmonary dysplasia.

Mol Cell Pediatr 2016 Dec 3;3(1):18. Epub 2016 May 3.

Department of Neonatology and Pediatric Critical Care Medicine, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, Dresden, 01307, Germany.

Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, remains a major healthcare burden. Despite great progresses in perinatal medicine over the past decades, no cure for BPD has been found. The complex pathophysiology of the disease further hampers the development of effective treatment strategies, but recent insights into the biology of mesenchymal stem (MSCs) and progenitor cells in lung development and disease have ignited the hope of preventing or even treating BPD. The promising results of pre-clinical studies have lead to the first early phase clinical trials. However, these treatments are experimental and much more needs to be learned about the mechanism of action and manufacturing of MSCs. In this mini review, we briefly summarize the role of resident and exogenous MSCs in the development and treatment of BPD.
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http://dx.doi.org/10.1186/s40348-016-0046-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854850PMC
December 2016

Neonatal assessment in the delivery room--Trial to Evaluate a Specified Type of Apgar (TEST-Apgar).

BMC Pediatr 2015 Mar 8;15:18. Epub 2015 Mar 8.

Children's Hospital, University of Göttingen, 37099, Göttingen, Germany.

Background: Since an objective description is essential to determine infant's postnatal condition and efficacy of interventions, two scores were suggested in the past but weren't tested yet: The Specified-Apgar uses the 5 items of the conventional Apgar score; however describes the condition regardless of gestational age (GA) or resuscitative interventions. The Expanded-Apgar measures interventions needed to achieve this condition. We hypothesized that the combination of both (Combined-Apgar) describes postnatal condition of preterm infants better than either of the scores alone.

Methods: Scores were assessed in preterm infants below 32 completed weeks of gestation. Data were prospectively collected in 20 NICU in 12 countries. Prediction of poor outcome (death, severe/moderate BPD, IVH, CPL and ROP) was used as a surrogate parameter to compare the scores. To compare predictive value the AUC for the ROC was calculated.

Results: Of 2150 eligible newborns, data on 1855 infants with a mean GA of 28(6/7) ± 2(3/7) weeks were analyzed. At 1 minute, the Combined-Apgar was significantly better in predicting poor outcome than the Specified- or Expanded-Apgar alone. Of infants with a very low score at 5 or 10 minutes 81% or 100% had a poor outcome, respectively. In these infants the relative risk (RR) for perinatal mortality was 24.93 (13.16-47.20) and 31.34 (15.91-61.71), respectively.

Conclusion: The Combined-Apgar allows a more appropriate description of infant's condition under conditions of modern neonatal care. It should be used as a tool for better comparison of group of infants and postnatal interventions.

Trial Registration: clinicaltrials.gov Protocol Registration System (NCT00623038). Registered 14 February 2008.
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http://dx.doi.org/10.1186/s12887-015-0334-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4374498PMC
March 2015

Mask CPAP during neonatal transition: too much of a good thing for some term infants?

Arch Dis Child Fetal Neonatal Ed 2015 Sep 15;100(5):F378-9. Epub 2015 Apr 15.

Division of Neonatology and Paediatric Intensive Care, Department of Paediatrics, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Germany.

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http://dx.doi.org/10.1136/archdischild-2015-308236DOI Listing
September 2015

Apgar score and risk of cause-specific infant mortality.

Lancet 2015 Feb;385(9967):505-6

Department of Neonatology and Pediatric Intensive Care, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

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http://dx.doi.org/10.1016/S0140-6736(15)60196-9DOI Listing
February 2015

Influences of a dedicated parental training program on parent-child interaction in preterm infants.

Early Hum Dev 2015 Mar 9;91(3):205-10. Epub 2015 Feb 9.

Neonatologie & Pädiatrische Intensivmedizin am Universitätsklinikum Dresden, Germany. Electronic address:

Objective: To investigate influences on the interaction between preterm infants and their parents by a dedicated parental training program on the care of preterm infants.

Methods: Standardized scenarios of mother-child interactions (50 mother-child dyads of very low birth weight infants (VLBWI), birth weight<1500g) were videotaped in two perinatal centers (PC-A, PC-B). The videos were reviewed and scored using a standardized instrument. In both centers, parents were integrated in the daily care by pediatric nurses, while additionally PC-A had a structured parental training program.

Results: PC-A and PC-B were comparable regarding patient spectrum and number of admissions of VLBWIs/year. Both centers had similar care values with respect to the "baby friendly" initiative. No significant differences were seen in characteristics of patients (gestational age, birth weight, postnatal age) and mothers (age, parity, marital status, professions). However, in scoring the mother-child interactions significant differences were observed: In contrast to PC-B the recorded behavior in mother-child dyads of PC-A was significantly more often scored as interaction-oriented.

Conclusion: A dedicated, structured, and actively encouraging training program for parents of preterm infants was found to be more strongly correlated toward neurodevelopmental enhancing mother-child-interactions than an approach of merely integrating parents into daily care routine.
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http://dx.doi.org/10.1016/j.earlhumdev.2015.01.012DOI Listing
March 2015

Suctioning habits in the delivery room and the influence on postnatal adaptation - a video analysis.

J Perinat Med 2015 Nov;43(6):777-82

Aims: To determine how often infants are suctioned during delivery and how it affects the neonate.

Methods: Single-center analysis of video-recorded delivery room management after c-section from January 2012 until April 2013. Time point, duration, and frequency of suctioning in term and preterm newborns were analyzed along with vital parameters (heart rate (HR) and saturation values).

Results: Three hundred forty-six videos were analyzed. Twenty-three percent of term and 66% of preterm newborns were suctioned. Newborns were suctioned up to 14 times; total duration spent for suctioning was between 2 and 154 s. Suctioning before face mask application occurred in 31% of the suctioned newborns requiring respiratory support. No severe bradycardia (<60 bpm) was noticed. Suctioning did not have an effect on HR and saturation in preterm infants but was associated with significantly higher HR in term infants requiring respiratory support. Term infants who did not require respiratory support showed significantly higher saturation values at 3, 5, 6, 7, 8, 9, and 10 min if they were not suctioned.

Conclusions: Suctioning of newborns in the delivery room does not adhere to recommendations of international guidelines. However, previously described side effects of suctioning could not be confirmed.
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http://dx.doi.org/10.1515/jpm-2014-0188DOI Listing
November 2015

Analyzing support of postnatal transition in term infants after c-section.

BMC Pregnancy Childbirth 2014 Jul 11;14:225. Epub 2014 Jul 11.

Department of Neonatology and Pediatric Intensive Care, Medizinische Fakultät Carl Gustav Carus, TU Dresden, Fetscherstraße 74, Dresden 01307, Germany.

Background: Whereas good data are available on the resuscitation of infants, little is known regarding support of postnatal transition in low-risk term infants after c-section. The present study was performed to describe current delivery room (DR) management of term infants born by c-section in our institution by analyzing videos that were recorded within a quality assurance program.

Methods: DR- management is routinely recorded within a quality assurance program. Cross-sectional study of videos of term infants born by c-section. Videos were analyzed with respect to time point, duration and number of all medical interventions. Study period was between January and December 2012.

Results: 186 videos were analyzed. The majority of infants (73%) were without support of postnatal transition. In infants with support of transition, majority of infants received respiratory support, starting in median after 3.4 minutes (range 0.4-14.2) and lasting for 8.8 (1.5-28.5) minutes. Only 33% of infants with support had to be admitted to the NICU, the remaining infants were returned to the mother after a median of 13.5 (8-42) minutes. A great inter- and intra-individual variation with respect to the sequence of interventions was found.

Conclusions: The study provides data for an internal quality improvement program and supports the benefit of using routine video recording of DR-management. Furthermore, data can be used for benchmarking with current practice in other centers.
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http://dx.doi.org/10.1186/1471-2393-14-225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096413PMC
July 2014

Individual course of cranial symmetry and proportion in preterm infants up to 6 months of corrected age.

Early Hum Dev 2014 Sep 21;90(9):511-5. Epub 2014 Apr 21.

Department of Neonatology and Pediatric Intensive Care, Medizinische Fakultät Carl Gustav Carus an der TU Dresden, Germany.

Introduction: A significant proportion of preterm infants have dolichocephaly and/or deformational plagiocephaly (DP) at term equivalent age. However, quantitative data on the clinical course after discharge is limited in these infants.

Aims: To quantify the individual course of cranial symmetry and proportion in infants born <32 gestational weeks up to six months of corrected age (CA) and to investigate, whether measurements at discharge predict subsequent cranial deformations.

Methods: A total of 56 infants were examined at discharge, three and six months of CA. Cranial proportion and symmetry were quantified using a 3D laser scan method. Classification and prevalence data were obtained using age related reference values. Predictive value of DP at discharge regarding subsequent deformation was evaluated.

Results: Cranial Vault Asymmetry Index was 3.9% at discharge, 4.5% at three months and 3.7% at six months of CA. Prevalence of DP was 34% at discharge, 46% at three months and 27% at six months. Cranial Index was 71.4% at discharge and constantly increased over the examination period. Prevalence of dolichocephaly was high at discharge (77%) and subsequently decreased. While severe DP at discharge was predictive for a persistent deformation (PPV 0.78), 46% of infants without DP at discharge developed DP by six months of CA.

Discussion: Despite a high prevalence at discharge, the decreased prevalence of DP and dolichocephaly at six months of CA suggests an optimistic course. However, changes in head shape are hardly predictable for the individual infant. Thus, an accurate quantification should be part of neonatal follow-up programs.
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http://dx.doi.org/10.1016/j.earlhumdev.2014.03.008DOI Listing
September 2014

Positioning of term infants during delivery room routine handling - analysis of videos.

BMC Pediatr 2014 Feb 4;14:33. Epub 2014 Feb 4.

Department of Neonatology and Pediatric Intensive Care, Medizinische Fakultät Carl Gustav Carus, TU Dresden, Fetscherstraße 74, Dresden 01307, Germany.

Background: Delivery room management (DR) of the newly born infant should be performed according to international guidelines, but no recommendations are available for an infant's position immediately after birth. The present study was performed to answer the following questions: 1. How often is DR-management performed in term infants in side position? 2. Is routine DR-management possible in side position? 3. Is there any benefit of side position with respect to agitation or vital parameters?

Methods: Cross-sectional study of video-recorded DR-management in term newborns delivered by C-section in 2012. Videos were analysed for infant's position, administered interventions, vital parameters and agitation.

Results: 187 videos were analysed. The Main Position (defined as position spent more than 70% of the time) was "supine" in 91, "side" in 63 and "not determinable" in 33 infants. "Supine" infants received significantly (p < 0.001) more often stimulation (12.5% of the total time) than "side" infants (3.9% of time). There were no differences between both groups with regard to suctioning; CPAP was exclusively (98%) administered in supine position. Newborns on side were less agitated than those on supine. There was a trend towards a better oxygenation in "side" positioned infants (p = 0.055) and significantly (p = 0.04) higher saturation values in "left-sided" infants than "right-sided" infants at 8th minute. "Side" positioned infants reached oxygen saturation values >90% earlier than "supine" positioned infants (p = 0.16).

Conclusions: DR-management is feasible in the side position in term infants. Side position seems to be associated with reduced agitation and improved oxygenation. However, it remains unclear whether this represents a causal relationship or an association. The study supports the need for a randomized controlled trial.
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http://dx.doi.org/10.1186/1471-2431-14-33DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3922774PMC
February 2014

[Health insurance expenses for children in the first five years of life - a cohort-based analysis].

Z Evid Fortbild Qual Gesundhwes 2013 29;107(7):451-60. Epub 2013 Sep 29.

Universitätsklinikum Carl Gustav Carus, Dresden.

Introduction: The development of paediatrics is characterised by several changes in the past few years, concerning, in particular holistic treatments or preventive check-ups, but also the transfer of treatment from the inpatient to the outpatient sector. There are no reference values for assessing emerging health insurance expenses. The aim of this study was to obtain a frame of reference for the costs of the treatment for neonates, infants, and young children using the example of the expenditures of one health insurance fund.

Methods: The individual health insurance expenditures were analysed for the first five years of life of children insured with the AOK PLUS in Saxony, Germany, in 2005. Costs of hospital treatment, ambulatory care, remedies, tools, medicines and care were included.

Results: The costs per insured child and year amounted to approximately 1,277 Euro (N = 11,147), with the highest costs arising in the first two years. 858 Euro were spent annually for an "average" child; 5,691 Euro per year incurred for a child with special medical needs.

Discussion: The present cost analysis describes both the height and structure of a health insurance's spendings on children within the first five years of their life in consideration of regional medical care offers. The question of whether this analysis provides valid reference values for other health insurances or other service areas will have to be answered by other analyses.
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http://dx.doi.org/10.1016/j.zefq.2013.08.015DOI Listing
August 2014

Prevalence of head deformities in preterm infants at term equivalent age.

Early Hum Dev 2013 Dec 6;89(12):1041-7. Epub 2013 Sep 6.

Department of Neonatology and Pediatric Intensive Care, University Hospital Carl Gustav Carus, Dresden, Germany.

Introduction: Due to a rising number of head deformities in healthy newborns, there has been an increasing interest in nonsynostotic head deformities in children over recent years. Although preterm infants are more likely to have anomalous head shapes than term newborns, there is limited data available on early prevalence of head deformities in preterm infants.

Aims: The purposes of the present study were to acquire quantitative data on head shape of preterm infants at Term Equivalent Age (TEA), to determine the prevalence of symmetrical and asymmetrical head deformities and to identify possible risk factors.

Methods: In a cross-sectional study design, Cranial Vault Asymmetry Index (CVAI) and Cranial Index (CI) calculated from routine head-scans with a non-invasive laser shape digitizer were recorded and categorized in type and severity of deformation for three different groups of gestational age. Perinatal and postnatal patient data was tested for possible associations.

Results: Scans of 195 infants were included in the study. CVAI at TEA was higher in very preterm (4.1%) compared to term and late preterm infants. Prevalence of deformational plagiocephaly was 38% in very preterm infants. CI was lower in very (71.4%) and late (77.2%) preterm infants compared to term infants (80.0%). Compared to term babies (11%), a large number of very (73%) and late (28%) preterm infants exhibited dolichocephaly at TEA.

Discussion: Prevalence of symmetrical and asymmetrical head deformities in preterm infants is high at TEA. Interventions are required to prevent head deformities in preterm infants during the initial hospital stay.
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http://dx.doi.org/10.1016/j.earlhumdev.2013.08.011DOI Listing
December 2013

Improved weight gain in very-low-birth-weight infants after the introduction of a self-created computer calculation program for individualized parenteral nutrition.

Pediatr Neonatol 2014 Feb 31;55(1):41-7. Epub 2013 Jul 31.

Department of Pediatrics II (Neonatology), Innsbruck Medical University, Innsbruck, Austria. Electronic address:

Background: Although 90% of babies <1500 g (very-low-birth-weight or VLBW) are appropriate for gestational age (AGA) at birth, almost all are small for gestational age at 36 weeks of gestation, mainly due to nutritional deficiency in the first weeks of life. A computer calculation program (CCP) to calculate parenteral nutrition (PN) was introduced to improve nutritional intake in preterm infants.

Methods: Somatometric data and composition of PN of VLBW infants were compared with two points of time measured over a period of 4 years.

Results: Data from 56 patients born before the introduction of the CCP (2001-2002) and 59 patients born after the introduction of the CCP (2004-2005) were obtained. Although the number of AGA infants at birth did not differ, the computer-calculated group had significantly more AGA infants at the time of discharge from hospital (44% vs. 14%, p < 0.05). In this group, more protein and fat were administered in the first 5 days of life (7.3 g/kg vs. 4.5 g/kg, p < 0.05 and 5 g/kg vs. 0.5 g/kg, p < 0.05) and the duration of total PN was shorter (16 days vs. 24 days, p < 0.05).

Conclusion: Because the CCP contributes to a better weight gain in VLBW infants due to simplification of PN calculation, we suggest its use in the calculation of PN in VLBW infants.
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http://dx.doi.org/10.1016/j.pedneo.2013.05.010DOI Listing
February 2014

A comparison of conventional surfactant treatment and partial liquid ventilation on the lung volume of injured ventilated small lungs.

Physiol Meas 2013 Aug 26;34(8):915-24. Epub 2013 Jul 26.

Clinic of Neonatology, Charité University Medicine, Berlin, Germany.

As an alternative to surfactant therapy (ST), partial liquid ventilation (PLV) with perfluorocarbons (PFC) has been considered as a treatment for acute lung injury (ALI) in newborns. The instilled PFC is much heavier than the instilled surfactant and the aim of this study was to investigate whether PLV, compared to ST, increases the end-expiratory volume of the lung (VL). Fifteen newborn piglets (age <12 h, mean weight 678 g) underwent saline lung lavage to achieve a surfactant depletion. Thereafter animals were randomized to PLV (n = 8), receiving PFC PF5080 (3M, Germany) at 30 mL kg(-1), and ST (n = 7) receiving 120 mg Curosurf®. Blood gases, hemodynamics and static compliance were measured initially (baseline), immediately after ALI, and after 240 min mechanical ventilation with either technique. Subsequently all piglets were killed; the lungs were removed in toto and frozen in liquid N2. After freeze-drying the lungs were cut into lung cubes (LCs) with edge lengths of 0.7 cm, to calculate VL. All LCs were weighed and the density of the dried lung tissue was calculated. No statistically significant differences between treatment groups PLV and ST (means ± SD) were noted in body weight (676 ± 16 g versus 679 ± 17 g; P = 0.974) or lung dry weight (1.64 ± 0.29 g versus 1.79 ± 0.48 g; P = 0.48). Oxygenation index and ventilatory efficacy index did not differ significantly between both groups at any time. VL (34.28 ± 6.13 mL versus 26.22 ± 8.1 mL; P < 0.05) and the density of the dried lung tissue (48.07 ± 5.02 mg mL(-1) versus 69.07 ± 5.30 mg mL(-1); P < 0.001), however, differed significantly between the PLV and ST groups. A 4 h PLV treatment of injured ventilated small lungs increased VL by 30% and decreased lung density by 31% compared to ST treatment, indicating greater lung distension after PLV compared to ST.
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http://dx.doi.org/10.1088/0967-3334/34/8/915DOI Listing
August 2013

Bacterial contamination of mechanically extracted breast milk.

Am J Perinatol 2014 Apr 13;31(4):293-8. Epub 2013 Jun 13.

Department for Neonatology and Pediatric Intensive Care Medicine, Klinik für Kinder- und Jugendmedizin Universitätsklinikum Carl Gustav Carus, Dresden, Germany.

Objective: Positive effects of breast milk feeding for preterm newborns have been demonstrated but bacterial contamination of mechanically expressed breast milk may cause neonatal sepsis. Pasteurizing breast milk reduces the bacterial count but impairs helpful nutrients. The aim of the study was (1) to analyze bacterial concentration in expressed breast milk and (2) to clarify if procedures after extraction cause an increase of bacterial contamination.

Study Design: Routine bacterial breast milk cultures of newborns < 32 weeks of gestational age were analyzed retrospectively from the year 2010. Serial milk cultures from both breasts of 50 mothers, the collecting bottle, and the in-house milk bank were tested prospectively.

Results: Forty percent of milk samples from 2010 contained more than 100,000 colony-forming units (CFU) per milliliter or more than 10,000 CFU/mL potential pathogenic bacteria. In the prospective study no significant differences in bacterial concentration after breast milk extraction were observed.

Conclusion: High concentrations of bacteria are frequently observed in expressed breast milk. The study provides evidence that these bacteria are in the breast milk directly after emission. The pumping procedure and further transportation to the milk bank are of no influence.
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http://dx.doi.org/10.1055/s-0033-1348028DOI Listing
April 2014

Pulmonary surfactant preserves viability of alveolar type II cells exposed to polymyxin B in vitro.

PLoS One 2013 19;8(4):e62105. Epub 2013 Apr 19.

Department of Pediatrics, University of Luebeck, Luebeck, Germany.

Background: Exogenous surfactant derived from animal lungs is applied for treatment of surfactant deficiency. By means of its rapid spreading properties, it could transport pharmaceutical agents to the terminal air spaces. The antimicrobial peptide Polymyxin B (PxB) is used as a topical antibiotic for inhalation therapy. Whereas it has been shown that PxB mixed with surfactant is not inhibiting surface activity while antimicrobiotic activity is preserved, little is known concerning the effects on synthesis of endogenous surfactant in alveolar type II cells (ATIIC).

Objective: To investigate ATIIC viability and surfactant-exocytosis depending on PxB and/or surfactant exposure.

Methods: ATIIC were isolated from rat lungs as previously described and were cultivated for 48 h. After incubation for a period of 1-5 h with either PxB (0.05 or 0.1 mg/ml), modified porcine surfactant (5 or 10 mg/ml) or mixtures of both, viability and exocytosis (spontanously and after stimulation) were determined by fluorescence staining of intracellular surfactant.

Results: PxB 0.1 mg/ml, but not porcine surfactant or porcine surfactant plus PxB reduces ATIIC-viability. Only PxB alone, but not in combination with porcine surfactant, rapidly reduces fluorescence in ATIIC at maximum within 3 h, indicating stimulation of exocytosis. Subsequent ionomycin-stimulation does not further increase exocytosis of PxB incubated ATIIC. In presence of surfactant, stimulating effects of PxB and ionomycin on exocytosis are reduced.

Conclusion: PxB alone shows negative effects on ATIIC, which are counterbalanced in mixtures with surfactant. So far, our studies found no results discouraging the concept of a combined treatment with PxB and surfactant mixtures.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0062105PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3631157PMC
November 2013

Three-dimensional digital capture of head size in neonates - a method evaluation.

PLoS One 2013 8;8(4):e61274. Epub 2013 Apr 8.

Department of Neonatology and Paediatric Intensive Care, University Hospital Carl Gustav Carus, Dresden, Germany.

Introduction: The quality of neonatal care is mainly determined by long-term neurodevelopmental outcome. The neurodevelopment of preterm infants is related to postnatal head growth and depends on medical interventions such as nutritional support. Head circumference (HC) is currently used as a two-dimensional measure of head growth. Since head deformities are frequently found in preterm infants, HC may not always adequately reflect head growth. Laser aided head shape digitizers offer semiautomatic acquisition of HC and cranial volume (CrV) and could thus be useful in describing head size more precisely.

Aims: 1) To evaluate reproducibility of a 3D digital capture system in newborns. 2) To compare manual and digital HC measurements in a neonatal cohort. 3) To determine correlation of HC and CrV and predictive value of HC.

Methods: Within a twelve-month period data of head scans with a laser shape digitizer were analysed. Repeated measures were used for method evaluation. Manually and digitally acquired HC was compared. Regression analysis of HC and CrV was performed.

Results: Interobserver reliability was excellent for HC (bias-0.005%, 95% Limits of Agreement (LoA) -0.39-0.39%) and CrV (bias1.5%, 95%LoA-0.8-3.6%). Method comparison data was acquired from 282 infants. It revealed interchangeability of the methods (bias-0.45%; 95%LoA-4.55-3.65%) and no significant systematic or proportional differences. HC and CrV correlated (r(2) = 0.859, p<0.001), performance of HC predicting CrV was poor (RSD ±24 ml). Correlation was worse in infants with lower postmenstrual age (r(2) = 0.745) compared to older infants (r(2) = 0.843).

Discussion: The current practice of measuring HC for describing head growth in preterm infants could be misleading since it does not represent a 3D approach. CrV can vary substantially in infants of equal HC. The 3D laser scanner represents a new and promising method to provide reproducible data of CrV and HC. Since it does not provide data on cerebral structures, additional imaging is required.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0061274PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3620274PMC
October 2013

Continuous noninvasive monitoring of lung recruitment during high-frequency oscillatory ventilation by electrical impedance measurement: an animal study.

Neonatology 2013 25;103(3):218-23. Epub 2013 Jan 25.

Department of Neonatology and Paediatric Intensive Care, University Hospital Carl Gustav Carus Dresden, Dresden, Germany.

Background: Ventilatory pressures should target the range between the upper and lower inflection point of the pressure volume curve in order to avoid atelecto- and volutrauma. During high-frequency oscillatory ventilation (HFOV), this range is difficult to determine. Quadrant impedance measurement (QIM) has recently been shown to allow accurate and precise measurement of lung volume changes during conventional mechanical ventilation.

Objectives: To investigate if QIM can be used to determine a static pressure-residual impedance curve during a recruitment-derecruitment manoeuvre on HFOV and to monitor the time course of alveolar recruitment after changing mean airway pressure (MAP).

Methods: An incremental and decremental MAP trial (6 cm H2O to 27 cm H2O) was conducted in five surfactant-depleted newborn piglets during HFOV. Ventilatory, gas exchange and haemodynamic parameters were recorded. Continuous measurement of thoracic impedance change was performed.

Results: Mean residual impedance (RI) increased with each stepwise increase of MAP resulting in a total mean increase of +26.5% (±4.0) at the highest MAP (27 cm H2O) compared to baseline ventilation at 6 cm H2O. Upon decreasing MAP levels, RI fell more slowly compared to its ascent; 83.4% (±19.1) and 84.8% (±16.4) of impedance changes occurred in the first 5 min after an increase or decrease in airway pressure, respectively.

Conclusions: QIM could be used for continuous monitoring of thoracic impedance and determination of the pressure-RI curve during HFOV. The method could prove to be a promising bedside method for the monitoring of lung recruitment during HFOV in the future.
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http://dx.doi.org/10.1159/000345612DOI Listing
August 2013

Persurf, a new method to improve surfactant delivery: a study in surfactant depleted rats.

PLoS One 2012 17;7(10):e47923. Epub 2012 Oct 17.

Department for Neonatology and Pediatric Intensive Care Medicine, Klinik für Kinderheilkunde, Universitätsklinikum Carl Gustav Carus, Medizinische Fakultät der Technischen Universität Dresden, Dresden, Germany.

Purpose: Exogenous surfactant is not very effective in adults with ARDS, since surfactant does not reach atelectatic alveoli. Perfluorocarbons (PFC) can recruit atelectatic areas but do not replace impaired endogenous surfactant. A surfactant-PFC-mixture could combine benefits of both therapies. The aim of the proof-of-principal-study was to produce a PFC-in-surfactant emulsion (Persurf) and to test in surfactant depleted Wistar rats whether Persurf achieves I.) a more homogenous pulmonary distribution and II.) a more homogenous recruitment of alveoli when compared with surfactant or PFC alone.

Methods: Three different PFC were mixed with surfactant and phospholipid concentration in the emulsion was measured. After surfactant depletion, animals either received 30 ml/kg of PF5080, 100 mg/kg of stained (green dye) Curosurf™ or 30 ml/kg of Persurf. Lungs were fixated after 1 hour of ventilation and alveolar aeration and surfactant distribution was estimated by a stereological approach.

Results: Persurf contained 3 mg/ml phospholipids and was stable for more than 48 hours. Persurf-administration improved oxygenation. Histological evaluation revealed a more homogenous surfactant distribution and alveolar inflation when compared with surfactant treated animals.

Conclusions: In surfactant depleted rats administration of PFC-in-surfactant emulsion leads to a more homogenous distribution and aeration of the lung than surfactant alone.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0047923PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3474734PMC
April 2013

Acupuncture for treatment of hospital-induced constipation in children: a retrospective case series study.

Acupunct Med 2012 Dec 21;30(4):258-60. Epub 2012 Aug 21.

Department of Paediatrics, Carl Gustav Carus-TU Dresden, Fetscher Str. 74, 01307, Dresden, Germany.

Objective: Acupuncture is a promising option in the treatment of functional bowel disorders. The aim of this study was to evaluate the feasibility and acceptance of acupuncture for the treatment of hospital-induced constipation (HIC) in children.

Methods: Bilateral stimulation of acupuncture point LI11 was applied in 10 children with HIC using fixed indwelling acupuncture needles (0.9 mm long) before considering starting conventional local constipation therapy with laxative suppositories. The clinical records were studied retrospectively for feasibility, acceptance and effectiveness of acupuncture.

Results: Acupuncture was feasible in all children and application of the indwelling needles was tolerated without fear. Side effects were not observed. After a median of 3 days of HIC, all children defaecated within 2 h after LI11 stimulation. No patient required conventional local constipation therapy.

Conclusions: Acupuncture for the treatment of HIC is feasible and acceptable. Its effect should be verified in a randomised controlled trial.
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http://dx.doi.org/10.1136/acupmed-2012-010192DOI Listing
December 2012

The expression of vascular endothelial growth factor and its receptors in congenital bronchopulmonary cystic malformations.

Eur J Pediatr Surg 2012 Apr 19;22(2):127-32. Epub 2012 Apr 19.

Department of Neonatology, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Background: Bronchopulmonary sequestration (BPS) and congenital cystic adenomatoid malformation (CCAM) represent rare hamartomatous abnormalities of the lung. Dysregulation of cytokines that influence pulmonary vasculogenesis and epithelial growth, both known to be altered in BPS and CCAM, may play a role in their pathogenesis.

Objective: We hypothesized that expression of vascular endothelial growth factor (VEGF) or its receptors might be altered in CCAM and BPS, possibly distinguishing CCAM from BPS, or from controls.

Methods: Lung biopsy specimens obtained from infants who had undergone surgery for BPS (n = 4) or CCAM (n = 5) within the first month of life and normal lung autopsy samples (n = 4) serving as controls were investigated immunohistochemically for the protein expression levels of VEGF and its corresponding receptors.

Results: VEGF, vascular endothelial growth factor receptor 1 (VEGFR1), vascular endothelial growth factor receptor 2 (VEGFR2), and vascular endothelial growth factor receptor 3 (VEGFR3) staining was detected in CCAM and BPS specimens, as well as in control samples. VEGFR2 expression increased from controls to CCAM and from CCAM to BPS, the difference between controls and BPS being significant. The expression of VEGF, VEGFR1, and VEGFR3 was similar among the three groups. Consistent with a possible involvement of VEGFR2 in altered vasculogenesis-bronchiogenesis interaction, its expression was predominantly found in bronchial but not alveolar regions.

Conclusions: The data suggest a possible role of VEGF-VEGFR2 interaction in the pathogenesis of congenital bronchopulmonary cystic malformations. However, VEGFR2 does not represent a suitable histochemical marker to distinguish between BPS and CCAM.
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http://dx.doi.org/10.1055/s-0032-1308692DOI Listing
April 2012

Preterm resuscitation I: clinical approaches to improve management in delivery room.

Early Hum Dev 2011 Nov 14;87(11):749-53. Epub 2011 Sep 14.

Department for Neonatology and Pediatric Intensive Care, Children's Clinic of the University Hospital Carl Gustav Carus, Fetscherstrasse 74, Dresden, Germany.

Delivery room (DR-) management has a great potential to optimise quality of long term outcome in extremely preterm infants. However, a new conceptual framework that focuses on an individualised 'support of transition' rather than on 'resuscitation' is necessary. Video-recordings of DR-management represent a valuable tool to improve care. Recording combined with a structured feed-back should be introduced in step-wise approach in clinical routine. To describe the postnatal condition of groups of infants or to compare interventions in a research setting, a numerical score-- representing the sum of several objective findings--is required. The conventional Apgar-Score has severe limitations that restrict its applicability. The Specified-Apgar allows an assessment of infant's condition independent of interventions and regardless of gestational age. The Expanded-Apgar quantifies the interventions needed to achieve the condition described by the Specified-Apgar. In summary, beside a new conceptual framework an individualised monitoring and an objective assessment of DR-management are required.
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http://dx.doi.org/10.1016/j.earlhumdev.2011.08.019DOI Listing
November 2011

Continuous non-invasive monitoring of tidal volumes by measurement of tidal impedance in neonatal piglets.

PLoS One 2011 7;6(6):e21003. Epub 2011 Jun 7.

Department of Neonatology and Paediatric Intensive Care, University Hospital Carl Gustav Carus, Dresden, Germany.

Background: Electrical Impedance measurements can be used to estimate the content of intra-thoracic air and thereby give information on pulmonary ventilation. Conventional Impedance measurements mainly indicate relative changes, but no information concerning air-volume is given. The study was performed to test whether a 3-point-calibration with known tidal volumes (VT) during conventional mechanical ventilation (CMV) allows subsequent calculation of VT from total Tidal-Impedance (tTI) measurements using Quadrant Impedance Measurement (QIM). In addition the distribution of TI in different regions of the thorax was examined.

Methodology And Principal Findings: QIM was performed in five neonatal piglets during volume-controlled CMV. tTI values at three different VT (4, 6, 8 ml/kg) were used to establish individual calibration curves. Subsequently, each animal was ventilated with different patterns of varying VT (2-10 ml/kg) at different PEEP levels (0, 3, 6, 9, 12 cmH(2)O). VT variation was repeated after surfactant depletion by bronchoalveolar lavage. VT was calculated from tTI values (VT(calc)) and compared to the VT delivered by the ventilator (VT(PNT)). Bland-Altman analysis revealed good agreement between VT(calc) and VT(PNT) before (bias -0.08 ml; limits of agreement -1.18 to 1.02 ml at PEEP = 3 cmH(2)O) and after surfactant depletion (bias -0.17 ml; limits of agreement -1.57 to 1.22 ml at PEEP = 3 cmH(2)O). At higher PEEP levels VT(calc) was lower than VT(PNT), when only one fixed calibration curve (at PEEP 3 cmH(2)O) was used. With a new calibration curve at each PEEP level the method showed similar accuracy at each PEEP level. TI showed a homogeneous distribution over the four assessed quadrants with a shift toward caudal regions of the thorax with increasing VT.

Conclusion: Tidal Impedance values could be used for precise and accurate calculation of VT during CMV in this animal study, when calibrated at each PEEP level.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0021003PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110249PMC
October 2011

Effect of exogenous surfactants on viability and DNA synthesis in A549, immortalized mouse type II and isolated rat alveolar type II cells.

BMC Pulm Med 2011 Feb 17;11:11. Epub 2011 Feb 17.

Innsbruck Medical University, Department for Pediatrics, Neonatology, Austria.

Background: In mechanically ventilated preterm infants with respiratory distress syndrome (RDS), exogenous surfactant application has been demonstrated both to decrease DNA-synthesis but also and paradoxically to increase epithelial cell proliferation. However, the effect of exogenous surfactant has not been studied directly on alveolar type II cells (ATII cells), a key cell type responsible for alveolar function and repair.

Objective: The aim of this study was to investigate the effects of two commercially available surfactant preparations on ATII cell viability and DNA synthesis.

Methods: Curosurf® and Alveofact® were applied to two ATII cell lines (human A549 and mouse iMATII cells) and to primary rat ATII cells for periods of up to 24 h. Cell viability was measured using the redox indicator resazurin and DNA synthesis was measured using BrdU incorporation.

Results: Curosurf® resulted in slightly decreased cell viability in all cell culture models. However, DNA synthesis was increased in A549 and rat ATII cells but decreased in iMATII cells. Alveofact® exhibited the opposite effects on A549 cells and had very mild effects on the other two cell models.

Conclusion: This study showed that commercially available exogenous surfactants used to treat preterm infants with RDS can have profound effects on cell viability and DNA synthesis.
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http://dx.doi.org/10.1186/1471-2466-11-11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3055216PMC
February 2011

Nutrition of preterm infants in relation to bronchopulmonary dysplasia.

BMC Pulm Med 2011 Feb 3;11. Epub 2011 Feb 3.

Medical University Innsbruck, Department for Pediatrics, Neonatology, Austria.

Background: The pathogenesis of bronchopulmonary dysplasia (BPD) is multifactorial. In addition to prenatal inflammation, postnatal malnutrition also affects lung development.

Methods: A retrospective study was performed to analyse during the first two weeks of life the total, enteral and parenteral nutrition of premature infants (<31 weeks, birth weight ≤1500 g) born between 08/04 and 12/06.

Results: Ninety-five premature infants were analysed: 26 with BPD (27 ± 1 weeks) and 69 without BPD (28 ± 1 weeks). There was no statistical significant difference in the total intake of fluids, calories, glucose or protein and weight gain per day in both groups. The risk of developing BPD was slightly increased in infants with cumulative caloric intake below the minimal requirement of 1230 kcal/kg and a cumulative protein intake below 43.5 g/kg. Furthermore, the risk of developing BPD was significantly higher when infants had a cumulative fluid intake above the recommended 1840 ml/kg. In infants who developed BPD, the enteral nutrition was significantly lower than in non-BPD infants [456 ml/kg (IQR 744, 235) vs. 685 (IQR 987, 511)]. Infants who did not develop BPD reached 50% of total enteral feeding significantly faster [9.6 days vs. 11.5].

Conclusions: Preterm infants developing BPD received less enteral feeding, even though it was well compensated by the parenteral nutrient supply. Data suggest that a critical minimal amount of enteral feeding is required to prevent development of BPD; however, a large prospective clinical study is needed to prove this assumption.
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http://dx.doi.org/10.1186/1471-2466-11-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3040142PMC
February 2011

Effects of perfluorocarbons on surfactant exocytosis and membrane properties in isolated alveolar type II cells.

Respir Res 2010 May 9;11:52. Epub 2010 May 9.

University Hospital Dresden, Department for Pediatric Intensive Care and Neonatology, Technical University Dresden, Germany.

Background: Perfluorocarbons (PFC) are used to improve gas exchange in diseased lungs. PFC have been shown to affect various cell types. Thus, effects on alveolar type II (ATII) cells and surfactant metabolism can be expected, data, however, are controversial.

Objective: The study was performed to test two hypotheses: (I) the effects of PFC on surfactant exocytosis depend on their respective vapor pressures; (II) different pathways of surfactant exocytosis are affected differently by PFC.

Methods: Isolated ATII cells were exposed to two PFC with different vapor pressures and spontaneous surfactant exocytosis was measured. Furthermore, surfactant exocytosis was stimulated by either ATP, PMA or ionomycin. The effects of PFC on cell morphology, cellular viability, endocytosis, membrane permeability and fluidity were determined.

Results: The spontaneous exocytosis was reduced by PFC, however, the ATP and PMA stimulated exocytosis was slightly increased by PFC with high vapor pressure. In contrast, Ionomycin-induced exocytosis was decreased by PFC with low vapor pressure. Cellular uptake of FM 1-43 - a marker of membrane integrity - was increased. However, membrane fluidity, endocytosis and viability were not affected by PFC incubation.

Conclusions: We conclude that PFC effects can be explained by modest, unspecific interactions with the plasma membrane rather than by specific interactions with intracellular targets.
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http://dx.doi.org/10.1186/1465-9921-11-52DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2876085PMC
May 2010

Inflammatory cytokine mRNA in monocytes is modified by a recombinant (SP-C)-based surfactant and porcine surfactant.

Methods Find Exp Clin Pharmacol 2009 Jun;31(5):317-23

Medical University Innsbruck, Department of Pediatrics and Neonatology, Austria.

Respiratory distress syndrome (RDS) is mainly caused by a deficiency of surfactant in structurally immature lungs. Therapy for RDS consists of mechanical ventilation and administration of exogenous surfactant. Animal-derived surfactant preparations that are used to treat newborn infants show inhibition of proinflammatory cytokines. There are no data available concerning the effects of the new generation of surfactants. In the present study, the effects of an animal-derived surfactant (Curosurf) and a synthetic surfactant (Venticute) on lipopolysaccharide (LPS)-induced inflammation were tested in human monocyte THP-1 cells. The effects were measured as changes in messenger RNA (mRNA) expression of the chemokine interleukin-8 (IL-8), proinflammatory TNF-alpha and the anti-inflammatory IL-10 cytokine. Both surfactant preparations inhibited the LPS-induced increase in TNF-alpha expression. A comparison of both preparations revealed a similar effect on IL-10 expression. However, IL-10 expression was higher after incubation with Venticute. Curosurf increased IL-8 expression at higher concentrations, but Venticute had no effect. The anti-inflammatory effect of an animal-derived surfactant and a new-generation synthetic surfactant preparation may influence postnatal pulmonary inflammation.
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http://dx.doi.org/10.1358/mf.2009.31.5.1380462DOI Listing
June 2009

Variations of Apgar score of very low birth weight infants in different neonatal intensive care units.

Acta Paediatr 2009 Sep 25;98(9):1433-6. Epub 2009 Jun 25.

Department of Neonatology and Pediatric Intensive Care, University Hospital Carl Gustav Carus Dresden, Dresden, Germany.

Objective: The Apgar score should be an objective method to assess the state of newborns; however, its applicability in preterm infants is hampered by large variations among different observers. The study tested whether physicians that give low scores to written case descriptions also apply lower scores to preterm infants.

Patients And Methods: Descriptions (BMJ 2004; 329: 143-4) were sent to 14 neonatal units. Physicians were asked to evaluate the Apgar (case score). From seven units Apgar scores of all very low birth weight infants (VLBW) born between January 2004 and December 2006 were obtained from charts (clinical score).

Results: In total, 121 physicians from 14 institutions (median 9, range 3-15) replied: 24 residents with <6-month and 28 with >6-month neonatal experience, and 69 consultants. The assessment of the case scores was very heterogeneous with large variations in respiration, muscle tone and reflexes. Clinical scores were obtained from 1000 VLBW infants. The score depended on the gestational age, with a median of 4 at 24 and 7 at 27 weeks. With one exception, centres that assigned low case scores had also low clinical scores.

Conclusion: There is considerable variation in assigning Apgar scores. Definitions are required to apply the Apgar score to infants under clinical conditions such as preterm delivery, resuscitation or artificial ventilation.
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http://dx.doi.org/10.1111/j.1651-2227.2009.01347.xDOI Listing
September 2009

Vascular endothelial growth factor as marker for tissue hypoxia and transfusion need in anemic infants: a prospective clinical study.

Pediatrics 2009 Mar;123(3):784-90

University Hospital Carl Gustav Carus Dresden, Department of Neonatology and Pediatric Intensive Care, Pediatrics, Fetscherstrasse 74, 01307 Dresden, Germany.

Objective: Oxygen-carrying capacity of blood is reduced in anemic infants because of low hemoglobin levels. Red blood cell transfusions become necessary if low hematocrit causes tissue hypoxia. No reliable parameters exist for detecting chronic tissue hypoxia. Vascular endothelial growth factor is upregulated by hypoxia; hence, elevated vascular endothelial growth factor levels may be a marker for tissue hypoxia and may indicate the need for red blood cell transfusions.

Methods: In a prospective study, plasma vascular endothelial growth factor levels were measured in 3 groups of infants suspected of requiring red blood cell transfusions to find a vascular endothelial growth factor cutoff value indicative of tissue hypoxia. The 3 groups were acute anemic (an episode of acute bleeding [hematocrit drop > 5%] per day); chronic anemic (hematocrit drop < 5% per day); and nontransfused (hematocrit drop < 5% per day) but not meeting clinical criteria for a transfusion. Blood was sampled before transfusion and again 48 hours after transfusion if required. Plasma vascular endothelial growth factor and erythropoietin concentrations were measured.

Results: Vascular endothelial growth factor concentrations were lower in acutely anemic compared with chronically anemic infants, whereas erythropoietin levels did not differ between these groups. The vascular endothelial growth factor concentration was <140 pg/mL in all acutely anemic infants, and this was deemed the threshold level indicating sufficient tissue oxygenation in subsequent analysis. We found that 30% of chronically anemic and 43% of nontransfused infants had vascular endothelial growth factor levels of >140 pg/mL. In transfused infants, with elevated vascular endothelial growth factor levels, red blood cell transfusion resulted in lowering of vascular endothelial growth factor concentrations.

Conclusions: Vascular endothelial growth factor concentrations of >140 pg/mL may indicate insufficient oxygen delivery to tissues and may serve as a marker of the need for transfusion or of tissue hypoxia in other diseases.
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http://dx.doi.org/10.1542/peds.2007-2304DOI Listing
March 2009

The expression of VEGF and its receptors in the human ductus arteriosus.

Pediatr Res 2008 Oct;64(4):340-5

Department of Neonatology, Humboldt University, 13353 Berlin, Germany.

Programmed proliferative degeneration of the human fetal ductus arteriosus (DA) preceding definite postnatal closure has a large developmental variability and is controlled by several signaling pathways. Among these vascular endothelial growth factor (VEGF) and its receptors (VEGF-Rs) play an important role. Until now, gestational age dependent expression of VEGF and its receptors has not been investigated in a large number of human DA tissue specimens. We examined protein expression of VEGF and the three VEGF-Rs immunohistochemically in 63 human fetal autopsy DA specimens of 11-38 wk gestation. Specimens were classified into different maturity stages according to their histologic appearance. VEGF and VEGF-Rs-staining was detected in all maturity stages. VEGF-staining was localized perinuclearly in all vascular layers and did not change during development. VEGF-R1 and VEGF-R3 expression was marked in the endothelium in early maturity stages and decreased during development. In contrast, -R2 predominated in the media in later developmental stages. Our results emphasize the importance of VEGF as a mediator during programmed proliferative degeneration of fetal DA and support the hypothesis that VEGF-R1 and VEGF-R3 are required for normal blood vessel development during embryogenesis. In contrast, VEGF-R2 is the predominant receptor in later angiogenic signaling.
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http://dx.doi.org/10.1203/PDR.0b013e318180a375DOI Listing
October 2008