High blood pressure, a red flag for the neonatal manifestation of urea cycle disorders.

Background: Neonatal manifestation of life-threatening hyperammonemic encephalopathy in urea cycle disorders (UCD) is often misdiagnosed as neonatal sepsis, resulting in significantly delayed start of specific treatment and poor outcome. The major aim of this study was to identify specific initial symptoms or signs to clinically distinguish hyperammonemic encephalopathy in neonates from neonatal sepsis in order to identify affected individuals with UCD and to start metabolic therapy without delay. Furthermore, we evaluated the impact of diagnostic delay, peak plasma ammonium (NH) concentration, mode of emergency treatment and transfer to a tertiary referral center on the outcome.

CD8/FOXP3-ratio in osteosarcoma microenvironment separates survivors from non-survivors: a multicenter validated retrospective study.

Osteosarcoma is the most common primary bone tumor characterized by juvenile onset, tumor heterogeneity, and early pulmonary metastasis. Therapeutic improvement stagnates since more than two decades. Unlike major malignancies, biomarkers as prognostic factors at time of diagnosis are missing.

Deleted in malignant brain tumors 1 (DMBT1) elicits increased VEGF and decreased IL-6 production in type II lung epithelial cells.

Background: Deleted in malignant brain tumors 1 (DMBT1) is an innate defence protein expressed in the lungs of preterm infants and adults. Recent studies showed that DMBT1 is important in angiogenesis and can bind to different growth factors including VEGF. We aimed at examining relationships between VEGF and IL-6 levels to DMBT1 expression in the lungs of preterm and term infants and in lung epithelial cells in vitro.

Neutrophil chemotaxis in cord blood of term and preterm neonates is reduced in preterm neonates and influenced by the mode of delivery and anaesthesia.

Bacterial infections, even without any perinatal risk factors, are common in newborns, especially in preterm neonates. The aim of this study was to evaluate possible impairment of neutrophil chemotaxis in term and preterm neonates compared with adults as well as neonates with different modes of delivery and anaesthesia. We analysed the expression of the adhesion molecule L-Selectin as well as shape change, spontaneous and N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced transmigration of neutrophils in a flow cytometric assay of chemotaxis after spontaneous delivery with Cesarian Section (CS) under spinal anaesthesia (mepivacaine, sufentanil), epidural anaesthesia (ropivacaine or bupivacaine, sufentanil) or general anaesthesia (ketamine, thiopental, succinylcholine).

[Correction of Acidosis in Neonatal Intensive-care Medicine: A National Survey].

Background: Metabolic acidosis is a common problem of patients on neonatal intensive care units. Only little data exists in literature and there are no clinical guidelines. The aim of this national survey was to assess criteria for correction of metabolic acidosis in neonatal patients and if there were effects to be observed.

The olive oil-based lipid clinoleic blocks leukocyte recruitment and improves survival during systemic inflammation: a comparative in vivo study of different parenteral lipid emulsions.

Although fish oil-based and olive oil-based lipid emulsions have been shown to exert anti-inflammatory functions, the immunomodulating properties of lipids are still controversial. Therefore, we investigated the anti-inflammatory effect of three different parenterally administered lipid emulsions in vivo: olive oil-based Clinoleic, fish oil-based Smoflipid, and soybean oil-based Lipofundin. We observed leukocyte recruitment in inflamed murine cremaster muscle using intravital microscopy and survival in a murine model of LPS-induced systemic inflammation and analyzed expression of leukocyte and endothelial adhesion molecules.

Managing neonatal severe sepsis in Germany: a preliminary survey of current practices.

Background: In 2002 and 2007, the American College of Critical Care Medicine (ACCCM) provided clinical guidelines for hemodynamic support of pediatric and neonatal patients in septic shock. In 2008 and 2013, the Surviving Sepsis Campaign (SSC) Guidelines Committee offered up-to-date clinical guidelines for the management of severe sepsis and septic shock in adults and in pediatric patients. The aim of this study was to assess the standard of care of neonates with severe sepsis and septic shock in German neonatal intensive care units (NICUs) with regard to variability in management and guideline conformity.

LPS- and LTA-induced expression of IL-6 and TNF-α in neonatal and adult blood: role of MAPKs and NF-κB.

As nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) seem to be critical mediators in the inflammatory response, we studied the effects of lipopolysaccharide (LPS) and lipoteichoic acid (LTA) on (a) the activation of NF-κB and MAPKs and (b) the expression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) with or without the specific inhibitors of these intracellular signal transduction pathways in neonatal cord and adult blood. TNF-α and IL-6 concentrations showed a sharp increase in the supernatants of cord and adult whole blood after stimulation. TNF-α concentrations were significantly higher, whereas IL-6 concentrations were tendentially lower in adult blood after stimulation.

RAGE controls leukocyte adhesion in preterm and term infants.

Background: Insufficient leukocyte recruitment may be one reason for the high incidence of life-threatening infections in preterm infants. Since the receptor of advanced glycation end products (RAGE) is a known leukocyte adhesion molecule and highly expressed during early development, we asked whether RAGE plays a role for leukocyte recruitment in preterm and term infants.

Methods: Leukocyte adhesion was analyzed in dynamic flow chamber experiments using isolated leukocytes of cord blood from extremely premature (<30 weeks of gestation), moderately premature (30-35 weeks of gestation) and mature neonates (>35 weeks of gestation) and compared to the results of adults.

Improved survival in osteosarcoma patients with atypical low vascularization.

Background: Osteosarcoma is considered a highly vascularized bone tumor with early metastatic dissemination through intratumoral blood vessels mostly into the lung. Novel targets for therapy such as tumor vascularization are highly warranted since little progress has been achieved in the last 30 years. However, proof of relevance for vascularization as a major prognostic parameter has been hampered by tumor heterogeneity, difficulty in detecting microvessels by immunohistochemistry, and small study cohorts.

First report of a Chinese strain of coxsackie B3 virus infection in a newborn in Germany in 2011: a case report.

Introduction: Enteroviruses commonly encounter babies and children and infections present in a wide variety of symptoms ranging from asymptomatic infection, benign illness, and aseptic meningitis, hand-foot-and-mouth disease to severe life-threatening disease. Some newborns develop severe disease in the first 2 weeks of life and long-term sequelae may occur among survivors.

Case Presentation: We present a case report of a Caucasian newborn baby boy with severe encephalitis and systemic coxsackievirus B3 infection.

Anti-inflammatory functions of protein C require RAGE and ICAM-1 in a stimulus-dependent manner.

By binding β 2-integrins both ICAM-1 and the receptor for advanced glycation end products (RAGE) mediate leukocyte recruitment in a stimulus-dependent manner. Using different inflammatory mouse models we investigated how RAGE and ICAM-1 are involved in anti-inflammatory functions of protein C (PC; Ceprotin, 100 U/kg). We found that, depending on the stimulus, RAGE and ICAM-1 are cooperatively involved in PC-induced inhibition of leukocyte recruitment in cremaster models of inflammation.

Osteosarcoma microenvironment: whole-slide imaging and optimized antigen detection overcome major limitations in immunohistochemical quantification.

Background: In osteosarcoma survival rates could not be improved over the last 30 years. Novel biomarkers are warranted to allow risk stratification of patients for more individual treatment following initial diagnosis. Although previous studies of the tumor microenvironment have identified promising candidates, novel biomarkers have not been translated into routine histopathology.

RAGE controls activation and anti-inflammatory signalling of protein C.

Aims: The receptor for advanced glycation endproducts, RAGE, is a multiligand receptor and NF-κB activator leading to perpetuation of inflammation. We investigated whether and how RAGE is involved in mediation of anti-inflammatory properties of protein C.

Methods And Results: We analyzed the effect of protein C on leukocyte adhesion and transmigration in WT- and RAGE-deficient mice using intravital microscopy of cremaster muscle venules during trauma- and TNFα-induced inflammation.

Treatment of neonatal abstinence syndrome in preterm and term infants.

Objective: Neonatal abstinence syndrome (NAS) is treated with a variety of drug preparations. With the optional treatment of NAS with chloral hydrate, phenobarbital or morphine the cumulative drug consumption of the mentioned drugs, the length of hospital stay and treatment duration was evaluated in preterm and term neonates.

Methods: Retrospective, uncontrolled study which evaluates different therapies of neonatal abstinence syndrome (NAS) in preterm and term neonates.

Feasibility of adjunct therapeutic hypothermia treatment for hyperammonemia and encephalopathy due to urea cycle disorders and organic acidemias.

Background: Children with urea cycle disorders (UCDs) or organic acidemias (OAs) and acute hyperammonemia and encephalopathy are at great risk for neurological injury, developmental delay, intellectual disability, and death. Nutritional support, intravenous alternative pathway therapy, and dialysis are used to treat severe hyperammonemia associated with UCDs and nutritional support and dialysis are used to treat severe hyperammonemia in OAs. Brain protective treatment while therapy is initiated may improve neurological and cognitive function for the lifetime of the child.

Anti-inflammatory effects of selected drugs on activated neonatal and adult neutrophils.

Aim: In view of the central role of granulocytic neutrophils in the context of inflammatory reactions, the present study focuses on anti-inflammatory effects of drugs on activated neutrophils in neonates and adults.

Methods: Sixteen blood samples of neonates and adults were investigated in a prospective study. Loss of deformability, morphological changes, and increases in neutrophil elastase were determined as measures of neutrophil activation due to incubation with the pro-inflammatory cytokine interleukin-8.

Flow behavior of fetal, neonatal and adult RBCs in narrow (3-6 μm) capillaries--Calculation and experimental application.

Background And Objectives: In capillaries with diameters less than those of resting RBCs, the cells have to deform to pass through such narrow vessels. Since RBCs of fetuses, neonates and adults differ in their geometrical properties the flow behavior of RBCs with different sizes in uniform tubes with diameters of 3 to 6 μm were studied by means of a micropipette system and a mathematical model. Assumptions in this model include an RBC flow velocity of 1 mm/s, axisymmetric cell shape and a gap between the RBC and the vessel wall that allows sufficient lubrication.

Cardiac amyloidosis induces up-regulation of Deleted in Malignant Brain Tumors 1 (DMBT1).

Background: Amyloidosis is a life-threatening protein misfolding disease and affects cardiac tissue, leading to heart failure, myocardial ischemia and arrhythmia. Amyloid deposits result in oxidative stress, inflammation and apoptosis. The purpose of this study was to examine the role of innate defense components, i.

CXCL1-triggered interaction of LFA1 and ICAM1 control glucose-induced leukocyte recruitment during inflammation in vivo.

It is well acknowledged that proinflammatory stimulation during acute hyperglycemia is able to aggravate inflammatory diseases. However, the mechanisms of proinflammatory effects of glucose are controversially discussed. We investigated leukocyte recruitment after intravenous injection of glucose in different inflammatory models using intravital microscopy.

High DMBT1 concentrations in breast milk correlate with increased risk of infection in preterm and term neonates.

Background: Human milk contains immune molecules involved in the protection of newborns against infections. We analyzed the concentration of Deleted in Malignant Brain Tumors 1 (DMBT1), a protein with functions in innate immunity, in breast milk.

Methods: DMBT1 was detected in breast milk by Western blotting and its concentration was quantified by ELISA in 95 breast milk samples collected from mothers of preterm and term neonates during the first four weeks after delivery.

Partnerships between Medical Centres and General Hospitals Providing Normal Care Standards in Gynaecology and Obstetrics in Germany.

Hospital managers and the heads of medical departments are nowadays being faced with ever increasing demands. It is becoming difficult for some small hospitals to find highly experienced or even experienced medical staff, to provide specific health-care services at break-even prices and to maintain their position in competition with other hospitals. On the other hand, large hospitals are facing enormous pressure in the investment and costs fields.

Inhibition of LPS-Induced Activation of Coagulation by p38 MAPK Inhibitor.

During Gram-negative sepsis, lipopolysaccharide (LPS) activates toll-like receptor (TLR) 4 and induces complex responses of immune system and coagulation. However, the underlying LPS signalling mechanism on coagulation activation remains complex. To determine the role of the intracellular signalling factors p38 mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), and c-Jun N-terminal kinase (JNK) in the procoagulant response to LPS, coagulation process of human whole blood exposed to specific inhibitors was measured by thrombelastography.

Lipid A decreases human erythrocytes deformability by increasing intracellular Ca(2+): effects of verapamil, staurosporine and the rho-kinase inhibitor Y-27632.

There are several reports demonstrating an involvement of bacterial toxins in the rigidity of red blood cells (RBC). The present study investigates the influence of E. coli F-583-Rd lipid A on RBC deformability under mechanical shear stress.

RAGE and ICAM-1 differentially control leukocyte recruitment during acute inflammation in a stimulus-dependent manner.

Background: The receptor for advanced glycation endproducts, RAGE, is involved in the pathogenesis of many inflammatory conditions, which is mostly related to its strong activation of NF-κB but also due to its function as ligand for the β2-integrin Mac-1. To further dissect the stimulus-dependent role of RAGE on leukocyte recruitment during inflammation, we investigated β2-integrin-dependent leukocyte adhesion in RAGE-/- and Icam1-/- mice in different cremaster muscle models of inflammation using intravital microscopy.

Results: We demonstrate that RAGE, but not ICAM-1 substantially contributes to N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced leukocyte adhesion in TNF-α-pretreated cremaster muscle venules in a Mac-1-dependent manner.