[Extremely premature infants--survival and lifespan at the limits of feasibility].
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Child Development↗
Biomedical subjects
Arnold Pollak
Publications and source records attributed to Arnold Pollak.
Differentiation of neuroblastoma cell line N1E-115 involves several signaling cascades.
No systematic searches for differential expression of signaling proteins (SP) in undifferentiated vs. differentiated cell lineages were published and herein we used protein profiling for this purpose. The NIE-115 cell line was cultivated and an aliquot was differentiated with dimethylsulfoxide (DMSO), that is known to lead to a neuronal phenotype. Cell lysates were prepared, run on two-dimensional gel electrophoresis followed by MALDI-TOF-TOF identification of proteins and maps of identified SPs were generated. Seven SPs were comparable, 27 SPs: GTP-binding/Ras-related proteins, kinases, growth factors, calcium binding proteins, phosphatase-related proteins were observed in differentiated NIE-115 cells and eight SPs of the groups mentioned above were observed in undifferentiated cells only. Switching-on/off of several individual SPs from different signaling cascades during the differentiation process is a key to understand mechanisms involved. The findings reported herein are challenging in vitro and in vivo studies to confirm a functional role for deranged SPs.
Brain Neoplasms↗
Isolation and structural analysis of peptide mimotopes for the disialoganglioside GD2, a neuroblastoma tumor antigen.
The disialoganglioside GalAcbeta1-4(NeuAcalpha2-8NeuAcalpha2-3)Galbeta1-4Glcbeta1-1Cer (GD2) is expressed on various tumors, including neuroblastoma, and was defined as a relevant tumor antigen. The monoclonal anti-GD2 antibody 14.18 is widely used for diagnostic purposes in neuroblastoma, and in its mouse/human chimeric form (ch14.18) now enters passive immunotherapeutic regimens in phase II clinical trials. This study aimed to generate structural mimics of the 14.18 epitope of GD2. Therefore, we used the ch14.18 antibody for selecting immunoreactive GD2 peptide mimotopes from a decamer phage display library. In all, 13 GD2 peptide mimics could be determined by biopanning and their specificity was demonstrated by exclusive recognition by the ch14.18 antibody. Furthermore, their nature of being GD2 mimics and their degree of mimicry was confirmed by competition with the natural antigen. When performing a comparative visualization of the GD2 epitope and selected mimotopes using a three-dimensional computer modeling system (BALLView), we demonstrated fitting of the GD2 molecule and the mimotopes in the antigen-binding pouch of a GD2 specific antibody. Moreover, the computer modeling argued for optimal affinity of the GD2 mimotopes. We thus provide evidence that the generation of GD2 peptide mimotopes is successful when using the neuroblastoma antibody ch14.18 for selection, and that this approach might offer a tool to develop a vaccination strategy against this malignant pediatric tumor.
Amino Acid Sequence↗
Early mechanical ventilation is deleterious after aspiration-induced lung injury in rabbits.
We investigated whether mechanical ventilation after aspiration is deleterious when started before surfactant therapy. Gas exchange and lung mechanics were measured in rabbits after aspiration either mechanically ventilated before or after lavage with diluted surfactant or Ringer's solution. Lung injury was induced by intratracheal instillation of 2 mL/kg of a betain/HCl pepsin mixture. After 30 min of spontaneous breathing, ventilation was started in 12 rabbits, which were then treated by lavage with diluted surfactant (15 mL/kg body weight; 5.3 mg/mL, group MVpre S) or with Ringer's solution (1 mL/kg; group MVpre R). Another 12 rabbits were treated by lavage while spontaneously breathing and were then connected to the ventilator (MVpost S and MVpost R). Sham control rabbits were mechanically ventilated for 4 h. At the end of experiment, PaO2/FiO2 ratio in MVpost S was five times higher than in MVpre S (P=0.0043). Lung mechanics measurements showed significant difference between MVpre S and MVpost S (P=0.0072). There was histopathologic evidence of decreased lung injury in MVpost S. Immediate initiation of ventilation is harmful when lung injury is induced by aspiration. Further investigations are needed to clarify whether the timing of lavage with diluted surfactant has an impact on the treatment of patients with aspiration or comparable types of direct lung injury.
Animals↗
Association between prenatal treatment and clinical manifestations of congenital toxoplasmosis in infancy: a cohort study in 13 European centres.
AIM: To determine the effectiveness of prenatal treatment for clinical manifestations of congenital toxoplasmosis. METHODS: We prospectively identified 255 live-born infants with congenital toxoplasmosis using prenatal or neonatal screening. We determined the effect of prenatal treatment on the risks of intracranial or ocular lesions in infancy, accounting for gestational age at maternal seroconversion. RESULTS: Prenatal treatment within 4 wk of seroconversion reduced the risk of intracranial lesions compared with no treatment (odds ratio, OR 0.28; 95% CI: 0.08-0.75), but there was no significant effect when initiated after 4 wk (OR 0.76; 95% CI: 0.35-1.59; overall p-value 0.19). Compared to spiramycin alone, no treatment doubled the risk of intracranial lesions (OR 2.33; 95% CI: 1.04-5.50), but the risk did not differ with pyrimethamine-sulphonamide treatment (overall p-value 0.52). There was no consistent relationship between the type or timing of treatment and the risk of ocular lesions. Gestational age at maternal seroconversion was inversely associated with the risk of intracranial but not ocular lesions. CONCLUSION: Only early versus no prenatal treatment for intracranial lesions showed a statistically significant benefit. A large randomized controlled trial and/or meta-analysis of individual patient data from cohort studies is required to confirm these findings.
Adult↗
Changes in thrombopoiesis and platelet reactivity in extremely low birth weight infants undergoing erythropoietin therapy for treatment of anaemia of prematurity.
Erythropoietin (Epo) is frequently administered to premature infants to stimulate erythropoiesis. There is evidence from studies in animals and healthy adults that Epo also interacts with thrombopoiesis and platelet function. This study investigates the effect of Epo therapy on platelet reactivity, peripheral platelet counts and thiazole orange-positive (TO+) platelets in extremely low birth weight (ELBW) infants. In a randomised-controlled trial, ELBW infants with a birth weight < or =800 g and a gestational age < or =32 weeks were either randomised to a group receiving Epo during the first weeks of life or to a control group. Our results show that thrombin receptor-activating peptide (TRAP-6) -induced expression of P-selectin increased significantly during the first two weeks of Epo treatment. With the exception of week five, the number of TO+ platelets was significantly higher during the first eight weeks in Epo-treated infants compared to controls. The increase of TO+ platelets was not paralleled by an increase in total platelet count. We can conclude that Epo therapy has a short-lasting effect on platelet reactivity toTRAP-6 in ELBW infants during the first two weeks of life. Furthermore, Epo therapy is associated with an increase in the number of TO+ platelets compared to controls.
Anemia, Neonatal↗
Is the use of early nasal CPAP associated with lower rates of chronic lung disease and retinopathy of prematurity? Nine years of experience with the Vermont Oxford Neonatal Network.
OBJECTIVE: The neonatal regional tertiary care center of the University of Vienna (VC) has been a member of the Vermont Oxford Neonatal Network (VONN) since 1994. During the period 1994--2002, important differences between the VC and the VONN in both pre- and postnatal management and in late morbidities such as chronic lung disease (CLD) and severe retinopathy of prematurity (ROP) were observed. We hypothesize that stabilization of very-low-birth-weight (VLBW) infants on nasal continuous positive airway pressure (NCPAP) immediately after birth, combined with a restrictive use of artificial ventilation, might be responsible for lower rates of CLD and ROP. PATIENTS AND METHODS: Obstetric and neonatal data for all 1299 VLBW infants (401-1500 g) from the VC were compared with corresponding data for the 201,167 VLBW infants from the VONN for the period 1994--2002 with regard to respiratory management and patient outcome. Morbidity criteria were in accordance with VONN definitions. RESULTS: The percentage range for treatment and morbidity criteria for the VC and VONN are related to differences among various years within the observation period. Infants were stabilized at birth on NCPAP in 45-86% of cases in the VC vs. 37-63% in the VONN, the rate of mechanical ventilation was 40-59% vs. 66-74%, and use of surfactant was 31-50% vs. 55-64%. CLD was diagnosed in 14-32% of cases in the VC vs. 27-39% in the VONN, discharge on supplemental oxygen took place in 2-4% vs. 12-17% of cases and ROP (stages III and IV) was found in 1-10% vs. 8-12%. CONCLUSION: The association of lower rates of CLD and ROP in the VC compared to the VONN might be related to differences in early respiratory management of VLBW infants at high risk of development of respiratory distress syndrome. This needs to be confirmed in a large multicenter trial.
Austria↗
Knowledge-based computer-aided decision support in prenatal toxoplasmosis screening (TempToxopert).
The development of TempToxopert aimed at assisting clinicians in analysing the results of prenatal toxoplasmosis screening tests. Expert knowledge about diagnostics, screening strategies, and treatment of toxoplasmosis during pregnancy was collected and represented as a rule-based decision graph. Based on actual and past individual findings, the system generates case-specific interpretative reports consisting of a diagnostic hypothesis, recommendations for further treatment, and interpretations of specific test results.
Animals↗
Patient with partial trisomy 9q and learning disability but no pyloric stenosis.
Partial trisomy of the long arm of chromosome 9 represents a very rare and heterogeneous group of chromosomal aberrations. Associated clinical features include learning disability and pyloric stenosis. We present the first patient to be reported with a duplication of the chromosome region 9q22.1-->q33. The patient (female, age 17 years) presented with growth retardation, microcephaly, facial dysmorphia, oesophageal atresia, aortic stenosis, ventricular septal defect, atrial septal defect II, hypothyroidism, and learning disability, but no pyloric stenosis. A review of all cases of partial trisomy 9q reported in the literature demonstrates that learning disability is a characteristic feature of this group of chromosomal aberrations. However, there are cases of duplications of the same chromosome 9 material, with and without pyloric stenosis. This study provides new information for future genetic counselling, especially in cases of prenatal diagnosis of partial trisomy 9q.
Abnormalities, Multiple↗
Perinatal asphyxia in the rat has lifelong effects on morphology, cognitive functions, and behavior.
Perinatal asphyxia (PA) is a major determinant of neurological morbidity and mortality in the neonatal period. Many studies have been investigating neurological deficits following PA, including seizures, cerebral palsy, mental retardation, as well as psychiatric deficits. Most research performed so far has been focusing on acute or subacute sequelae and has uncovered a variety of morphological, neurochemical, behavioral, and cognitive changes following PA. However, information on long-term sequelae of animals that underwent a period of PA is scanty. Perinatally asphyxiated rats at the end of their life span present with immunohistochemical and synaptic changes as well as changes in brain protein expression. Furthermore, deficits in cognitive function tested in the Morris water maze and changes in social behavior were described. In this review, we are summarizing and discussing reported effects of global PA on morphology, cognitive functions, and behavior in rats at the end of their life span.
Animals↗
Monocyte switch in neonates: high phagocytic capacity and low HLA-DR expression in VLBWI are inverted during gestational aging.
Pre-term neonates are at high risk to develop early-onset sepsis which possibly is caused by an immature immune system. Monocytes play a pivotal role as professional phagocytic and antigen-presenting cells in the innate immunity. In the present study, we investigated in monocytes from cord blood the expression of human leukocyte antigen (HLA)-DR as a marker for antigen-presenting capability, the expression of the high-affinity receptor for IgG (FcgammaRI/CD64), and the capacity to phagocytize non-opsonized Escherichia coli. We compared 70 infants in three groups according to their gestational age (group I: 20 very low birth weight infants (VLBWI), 24-31 weeks of gestation; group II: 25 pre-term infants, 32-36 weeks of gestation, and group III: 25 term neonates). The expression of CD64 as well as the phagocytic capacity of monocytes from cord blood were highest in VLBWI (p < 0.05 and p < 0.01, respectively). In contrast, HLA-DR expression was significantly (p < 0.05) diminished in VLBWI, which possibly leads to a reduced antigen-presenting capacity. We conclude that monocytes have different functional properties during gestational aging, which perhaps participate in the high incidence of infections in VLBWI.
Age Factors↗
Heparinase-modified thrombelastography in term and preterm neonates.
UNLABELLED: Thrombelastography (TEG) appears to be a promising test to assess coagulation in infants and children. TEG enables a rapid assessment of hemostatic function with only 300 microL of whole blood and provides information about plasmatic coagulation, platelet function, and fibrinolysis. In this study, we used TEG to assess the coagulation system of preterm and term neonates to determine the effects of their deficient coagulation factor levels on global hemostatic function. Heparinase-modified TEG, platelet and red blood cell count, plasma fibrinogen, and prothrombin time were assessed in four groups of clinically stable infants: severely preterm (gestational age [GA], 27-31 wk), moderately preterm (GA, 32-36 wk), term (GA, 36-40 wk), and former preterm (corrected GA, 34-40 wk). Healthy adult volunteers served as a control group. When compared with the adult group, thromboelastography revealed no defects in coagulation from groups of clinically stable infants, documenting the functional integrity of coagulation despite, in part, decreased conventional coagulation variables. Because clinically stable preterm and term infants show a relatively small incidence of bleeding, despite prolonged conventional coagulation tests, TEG may better reflect the hemostatic potential of these patients compared with conventional coagulation tests. IMPLICATIONS: This study assessed the coagulation of preterm and term infants by thrombelastography and found functional integrity of coagulation despite, in part, decreased conventional coagulation variables.
Adult↗
Amniotic cavity cultures, blood cultures, and surface swabs in preterm infants--useful tools for the management of early-onset sepsis?
AIMS: To evaluate the potential benefit of amniotic fluid and amniotic/placental membrane cultures for the management of early-onset sepsis in preterm infants. METHODS: The results of amniotic cavity cultures obtained during cesarean section and of peripheral blood cultures and surface swabs obtained from the preterm infant at the time of admission were analyzed with respect to the diagnosis of clinical sepsis in 221 preterm infants <34 weeks of gestation. RESULTS: 136 (61.5%) patients had negative amniotic cavity culture results or growth of contaminants, 56 (25.3%) had growth of Ureaplasma urealyticum, and 29 (13.1%) of other pathogens. The corresponding numbers for surface swabs were 82.8%, 11.6%, and 5.6%. A positive blood culture was found in only two neonates. Fifty-four patients (24.4%) had clinical early-onset sepsis. Patients with amniotic cavity culture results that were positive for other pathogens were significantly more likely to experience clinical sepsis than patients with negative culture results (51.7% vs 15.1%, OR 6.1, p<0.0001). Regarding surface swabs, this correlation did not reach statistical significance. CONCLUSION: The strong association between positive amniotic cavity culture results and clinical early-onset sepsis supports the existence of a causal relation and provides evidence for the potential value of amniotic and/or placental membrane sampling in the management of early-onset sepsis in preterm infants. Surface swabs add no additional information and hence should not be performed routinely.
Amnion↗
Reference values for amplitude-integrated electroencephalographic activity in preterm infants younger than 30 weeks' gestational age.
OBJECTIVE: To prospectively investigate the development of amplitude-integrated electroencephalographic (aEEG) activity during the first 2 weeks of life in neurologically normal and clinically stable preterm infants <30 weeks' gestational age (GA). PATIENTS AND METHODS: Infants with a GA of <30 weeks admitted to the neonatal intensive care unit of the Vienna University Children's Hospital (Vienna, Austria) were studied prospectively by using aEEG and cranial ultrasound. Clinically stable infants without clinical or sonographic evidence of neurologic abnormalities were eligible for inclusion in the reference group. The distribution of 3 background aEEG activity patterns (discontinuous low-voltage, discontinuous high-voltage, and continuous), presence of sleep-wake cycles, and number of bursts per hour in the reference group were determined by visual analysis. RESULTS: Seventy-five infants (median GA: 27 weeks; range: 23-29 weeks) were eligible for inclusion in the reference group and had aEEG recordings during the first 2 weeks of life available. Analysis of aEEG background activity showed that with higher GA the relative amount of continuous activity increased while discontinuous patterns decreased. The number of bursts per hour decreased with increasing GA. Cyclical changes in aEEG background activity resembling early sleep-wake cycles were observed in all infants. CONCLUSIONS: Normal values for aEEG background activity were determined in preterm infants <30 weeks' GA. Clinically stable and neurologically normal preterm infants exhibit at least 2 different patterns of aEEG activity. There is a correlation between the GA and the relative duration of continuous aEEG activity.
Circadian Rhythm↗
Pain and stress management in the Neonatal Intensive Care Unit--a national survey in Austria.
UNLABELLED: Neonates are sensitive to pain and vulnerable to both its short-term and long-term effects. Management of analgesia is thought to be hampered by lack of awareness that newborns are capable of experiencing pain and by fears about adverse effects associated with analgesics. The purpose of this study was to assess current medical practice in preventive analgesia and sedation in the neonate throughout Austria. This report details the results of a survey in 28 neonatal intensive care units (NICUs) in Austria. Data collection took place from October to December 2001. All NICUs reported the capability of newborns to experience and express pain and nearly all stated the possibility of pain affecting morbidity. Validated scores for pain assessment were used by 11% of NICUs, standardized protocols for analgesia existed in 75%, and 100% practiced non-pharmacological treatment strategies. The use of preventive measures in routinely performed painful procedures ranged from 8% to 96%. For example, only 8% of NICUs prevent distress and pain prior to umbilical vessel catheterization, 29% prior to subcutaneous injections and 46% prior to heel lancing. Nearly all NICUs apply analgesia before lumbar puncture and thoracic-drain placement, and all use analgesic and/or sedative medication in elective intubation. CONCLUSION: There is widespread awareness among neonatologists of the importance and effects of distress caused by pain in newborns. However, the necessity of providing sufficient analgesia is underestimated. Further information on the safety of analgesic drugs in neonatology is imperative.
Analgesics↗
A very low birth weight infant with Candida nephritis with fungus balls. Full recovery after pyelotomy and antifungal combination therapy.
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Amphotericin B↗
Methemoglobin formation in children with congenital heart disease treated with inhaled nitric oxide after cardiac surgery.
OBJECTIVE: Inhaled nitric oxide (NO) is used as a therapy of pulmonary hypertension in children after cardiac surgery. Hemoglobin binds to NO with great affinity and forms methemoglobin by oxidation in the erythrocyte. Once produced, methemoglobin is unable to transport and unload oxygen in the tissues. The amount of available hemoglobin in the body for oxygen transport is thereby reduced. Anemia, acidosis, respiratory compromise and cardiac disease may render patients more susceptible than expected for a given methemoglobin level. The goal of the present study was to review the cumulative effect of inhaled NO on methemoglobin formation in critically ill children. We therefore looked for methemoglobin levels in children with congenital heart disease after cardiac surgery who were treated with inhaled NO in a range of 5-40 ppm. METHODS: We retrospectively reviewed the medical charts of 38 children with congenital heart disease after cardiac surgery. We extracted demographic data and physiological measurements at the following time points: (1) T0 = before starting inhaled NO therapy, (2) T1 = 24 h after the beginning of inhaled NO therapy, (3) T2 = half-time therapy, (4) T3 = end of therapy, (5) T4 = 24 h after finishing inhaled NO therapy. RESULTS: The median duration of inhaled NO therapy was 5.5 days (interquartile range 6, range 2-29), NO concentrations at T1 and T2 were 16 ppm (10, 5-40) and 12.5 ppm (12.3, 2-40), respectively. The median cumulative dose of inhaled NO was 1699 ppm (2313, 193-7018). Methemoglobin levels increased moderately, but significantly, during therapy ( T0 vs T1 p<0.05 and T0 vs T2 p<0.001). The highest methemoglobin level measured was 3.9%. Methemoglobin levels correlated positively with the inhaled NO doses applied at T1 ( r(2)=0.8376; p<0.01) and at T2 ( r(2)=0.8945; p<0.01). At T1 the methemoglobin level correlated negatively with the T1 blood pH value. The overall mortality rate was 13.2% (5 of 38 study patients died). There was no significant difference in methemoglobin levels between survivors and non-survivors. CONCLUSION: We conclude from our data that the use of inhaled NO therapy for children with congenital heart disease after cardiac surgery in the described range of 5-40 ppm, resulting in a maximum of 4% methemoglobin blood level, is feasible and safe. However, we recommend the use of the minimal effective dose of inhaled NO and continuous monitoring of methemoglobin levels, especially in cases of anemia or sepsis in critically ill children.
Administration, Inhalation↗
Monocyte phagocytosis as a reliable parameter for predicting early-onset sepsis in very low birthweight infants.
BACKGROUND: Septic complications lead to a high mortality rate in very low birthweight infants (VLBWI). Therefore, prognostic markers for the development of sepsis attach importance to start an efficient therapy as early as possible. AIMS: Functional and phenotypical variables of blood monocytes in the cord and peripheral blood were investigated to evaluate the parameters for predicting early-onset and late-onset sepsis (nosocomial infections). STUDY DESIGN: In a prospective study, 25 VLBWI were investigated. METHODS: In the cord blood taken immediately after birth, the capacity of the monocytes to phagocytose non-opsonized E. coli bacteria by flow cytometry and the ex-vivo production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6 (enzyme-linked immunoassay (ELISA)) after lipopolysaccharide (LPS) stimulation were measured. At the third day, the HLA-DR expression on the monocytes (flow cytometry) and the LPS-induced cytokine production were measured from the peripheral blood. RESULTS: Five VLBWI already developed early septic complications after 24-72 h, while the other three infants had late-onset sepsis 10-18 days after birth. The prognostic significance for early-onset sepsis was highest for the decreased monocyte phagocytic capacity (sensitivity and specificity: 100%) and for the LPS-induced formation of TNF-alpha and IL-1 beta in cord blood. Moreover, in septic VLBWI, the HLA-DR expression on the monocytes was lowered on day 3 after birth. The prognostic significance for late-onset sepsis was highest for TNF-alpha and IL-1 beta levels in the peripheral blood on the third day after birth. CONCLUSIONS: The determination of phagocytosis in the cord blood seems to be a reliable parameter for predicting early-onset sepsis and offers the possibility for a forward start of an antibiotic therapy.
Biomarkers↗