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Introduction: Pulmonary Surfactant reduces surface tension in the terminal airways thus facilitating breathing and contributes to host's innate immunity. Surfactant Proteins (SP) A, B, C and D were recently identified as inherent proteins of the CNS. Aim of the study was to investigate cerebrospinal fluid (CSF) SP levels in hydrocephalus patients compared to normal subjects. Patients and methods: CSF SP A-D levels were quantified using commercially available ELISA kits in 126 patients (0±84 years, mean 39 years). 60 patients without CNS pathologies served as a control group. Hydrocephalus patients were separated in aqueductal stenosis (AQS, n = 24), acute hydrocephalus without aqueductal stenosis (acute HC w/o AQS, n = 16) and idiopathic normal pressure hydrocephalus (NPH, n = 20). Furthermore, six patients with pseudotumor cerebri were investigated. Results: SP AÐD are present under physiological conditions in human CSF. SP-A is elevated in diseases accompanied by ventricular enlargement (AQS, acute HC w/o AQS) in a significant manner (0.67, 1.21 vs 0.38 ng/ml in control, p<0.001). SP-C is also elevated in hydrocephalic conditions (AQS, acute HC w/o AQS; 0.87, 1.71 vs. 0.48 ng/ml in controls, p<0.001) and in Pseudotumor cerebri (1.26 vs. 0.48 ng/ml in controls, p<0.01). SP-B and SP-D did not show significant alterations. Conclusion: The present study confirms the presence of SPs in human CSF. There are significant changes of SP-A and SP-C levels in diseases affecting brain water circulation and elevation of intracranial pressure. Cause of the alterations, underlying regulatory mechanisms, as well as diagnostic and therapeutic consequences of cerebral SP's requires further thorough investigations.

Introduction: Pulmonary Surfactant reduces surface tension in the terminal airways thus facilitating breathing and contributes to host''s innate immunity. Surfactant Proteins (SP) A, B, C and D were recently identified as inherent proteins of the CNS. Aim of the study was to investigate cerebrospinal fluid (CSF) SP levels in hydrocephalus patients compared to normal subjects. Patients and methods: CSF SP A-D levels were quantified using commercially available ELISA kits in 126 patients (0±84 years, mean 39 years). 60 patients without CNS pathologies served as a control group. Hydrocephalus patients were separated in aqueductal stenosis (AQS, n = 24), acute hydrocephalus without aqueductal stenosis (acute HC w/o AQS, n = 16) and idiopathic normal pressure hydrocephalus (NPH, n = 20). Furthermore, six patients with pseudotumor cerebri were investigated. Results: SP AÐD are present under physiological conditions in human CSF. SP-A is elevated in diseases accompanied by ventricular enlargement (AQS, acute HC w/o AQS) in a significant manner (0.67, 1.21 vs 0.38 ng/ml in control, p<0.001). SP-C is also elevated in hydrocephalic conditions (AQS, acute HC w/o AQS; 0.87, 1.71 vs. 0.48 ng/ml in controls, p<0.001) and in Pseudotumor cerebri (1.26 vs. 0.48 ng/ml in controls, p<0.01). SP-B and SP-D did not show significant alterations. Conclusion: The present study confirms the presence of SPs in human CSF. There are significant changes of SP-A and SP-C levels in diseases affecting brain water circulation and elevation of intracranial pressure. Cause of the alterations, underlying regulatory mechanisms, as well as diagnostic and therapeutic consequences of cerebral SP''s requires further thorough investigations.

BACKGROUND: To determine whether the secretor gene fucosyltransferase (FUT)2 polymorphism G428A is predictive for adverse outcomes in a large cohort of very-low-birth weight (VLBW) infants. METHODS: We prospectively enrolled 2,406 VLBW infants from the population-based multicenter cohort of the German Neonatal network cohort (2009-2011). The secretor genotype (rs601338) was assessed from DNA samples extracted from buccal swabs. Primary study outcomes were clinical sepsis, blood-culture confirmed sepsis, intracerebral hemorrhage (ICH), necrotizing enterocolitis (NEC) or focal intestinal perforation requiring surgery, and death. RESULTS: Based on the assumption of a recessive genetic model, AA individuals had a higher incidence of ICH (AA: 19.0% vs. GG/AG: 14.9%, P = 0.04) which was not significant in the additive genetic model (muitivariable logistic regression analysis; allele carriers: 365 cases, 1,685 controls; OR: 1.2; 95% CI: 0.99-1.4; P = 0.06). Other outcomes were not influenced by FUT2 genotype in either genetic model. CONCLUSION: This large-scale multicenter study did not confirm previously reported associations between FUT2 genotype and adverse outcomes in preterm infants.

Objectives: To assess the influence of an infusion of clonidine 1 mu g/kg/hr on fentanyl and midazolam requirement in ventilated newborns and infants. Design: Prospective, double-blind, randomized controlled multicenter trial. Controlled trials. com/ISRCTN77772144. Setting: Twenty-eight level 3 German PICUs/neonatal ICUs. Patients: Ventilated newborns and infants: stratum I (1-28 d), stratum II, (29-120 d), and stratum III (121 d to 2 yr). Interventions: Patients received clonidine 1 mu g/kg/hr or placebo on day 4 after intubation. Fentanyl and midazolam were adjusted to achieve a defined level of analgesia and sedation according to Hartwig score. Measurements and Main Results: Two hundred nineteen infants were randomized; 212 received study medication, 69.7% were ventilated in the postoperative care and 30.3% for other reasons. Primary endpoint: consumption of fentanyl and midazolam in the 72 hours following the onset of study medication (main observation period) in the overall study population. The confirmatory analysis of the overall population showed no difference in the consumption of fentanyl and midazolam. Explorative age-stratified analysis demonstrated that in stratum I (n = 112) the clonidine group had a significantly lower consumption of fentanyl (clonidine: 2.1 +/- 1.8 mu g/kg/hr, placebo: 3.2 +/- 3.1 mu g/kg/hr; p = 0.032) and midazolam (clonidine: 113.0 +/- 100.1 mu g/kg/hr, placebo: 180.2 +/- 204.0 mu g/kg/hr; p = 0.030). Strata II (n = 43) and III (n = 46) showed no statistical difference. Sedation and withdrawal-scores were significantly lower in the clonidine group of stratum I (p < 0.001). Frequency of severe adverse events did not differ between groups. Conclusions: Clonidine 1 mu g/kg/hr in ventilated newborns reduced fentanyl and midazolam demand with deeper levels of analgesia and sedation without substantial side effects. This was not demonstrated in older infants, possibly due to lower clonidine serum levels.

In dieser Arbeit wird das in vivo-Verhalten der murinen Erythro- und Granulopoese, einschließlich der hämatopoetischer Stammzellen, unter dem Einfluß von exogen appliziertem G-CSF und Erythropoietin mit Hilfe eines mathematischen Kompartimentmodelles untersucht. Der Schwerpunkt liegt auf der Identifizierung von linienübergreifenden Wachstumsfaktoreffekten. Zu diesem Zweck werden experimentelle Daten mit den Modellsimulationen unter Berücksichtigung verschiedener Modellannahmen verglichen. Die experimentellen Daten für die Modellentwicklung stammen zum einem kleinen Teil aus der Literatur, hauptsächlich betrachtet wurden jedoch Daten einer kooperierenden niederländischen Arbeitsgruppe. Die beiden Wachstumsfaktoren wurden kontinuierlich und simultan mittels osmotischer Minipumpen subkutan über einen längeren Zeitraum appliziert. Die experimentellen Daten werden zunächst mit Hilfe eines nichtlinearen Regressionsmodelles analysiert und quantitativ beschrieben, wobei Interaktionseffekte zwischen den Wachstumsfaktoren besondere Berücksichtigung finden. Es wird dann ein umfassendes mathematischen Differentialgleichungsmodell der murinen Erythro- und Granulopoese unter Berücksichtigung der linienübergreifenden Wachstumsfaktoreffekte und Interaktionen aufgestellt. Es wird zunächst überprüft, ob sich die beobachteten Daten unter Simultanstimulation durch die einfache Zusammenschaltung zweier bereits existierender Einzelmodelle der Erythro- und Granulopoese ohne weitere Modellannahmen erklären lassen. Dazu werden Daten von normalen als auch splenektomierten Tieren berücksichtigt. Es zeigt sich nach Prüfung verschiedener Hypothesen, dass erst unter Annahme einer durch Erythropoietin potenzierten Amplifikation der primär G-CSF-abhängigen Zellstufe der lienalen CFU-GM die experimentell beobachteten Effekte erklärt werden können. Es wird außerdem gezeigt, daß sich mit demselben Modell und denselben Modellparametern die bei splenektomierten Tieren zu beobachtetende G-CSFabhängige E