Plasma levels of osteopontin from birth to adulthood

Aim Osteopontin (OPN) has been investigated as a biomarker for cancer and nonmalignant diseases during the last decades. Data about OPN as a potential biomarker in childhood diseases are still sparse, and reference values are not available in children. We aimed to establish reference values for children from birth to young adulthood and evaluate whether there are age‐, gender‐, and weight‐specific differences. Method Umbilical cord blood and blood plasma samples of 117 children were collected in the Children's Hospital of Saarland University in Homburg/Saar. OPN levels were measured by ELISA, and statistical analysis was performed using SPSS software. Results Neonates, infants, toddlers, young children, adolescents, and adults were divided into the following six age groups: newborns (birth), infancy and toddlers (0‐24 months), early childhood (3‐6 years), middle childhood (7‐11 years), adolescence (12‐18 years), and adults (> 18 years). Highest blood OPN levels were found in the group of 0‐1 years of age. OPN blood levels declined significantly with age (Spearman r = −0.874; P < 0.001). Conclusion Our work is the first prospective and systematic study analyzing OPN cord blood and blood plasma levels in children of all ages. It is the first study yielding reference values for different age groups from birth to young adulthood. Our data give insight on how OPN in umbilical cord blood and OPN in blood plasma are physiologically influenced during childhood development and growth with high OPN levels after birth and a constant age‐related decline until the age of 14, when OPN levels reach similar values to those measured in adults

Novel modified Peyton's approach for knowledge retention on newborn life support training in medical students

Aim We sought to improve retention of neonatal resuscitation skills by modifying step 3 through additional functional verbalisation in Peyton's four‐step approach (P4S). Methods Newborn life support (NLS) training was performed in a simulation‐based setting. In contrast to the traditional approach, students taught with the modified approach were requested to explain every step of their performance in Peyton's step 3. A total of 123 students were allocated into both experimental groups. Students were then assessed by megacode on day four (initial assessment) and 6 months (follow‐up assessment). Results Both groups showed similar scorings in the initial, follow‐up assessment and in mean change. On initial megacode, time to start with initial inflation and post‐resuscitation care was significantly faster in the control group. All showed a significant loss of performance irrespective of modification in step 3 in the follow‐up assessment. Only time until start with post‐resuscitation care shows a significant group difference in mean change between initial and follow‐up with increasing time in the control and decreasing time span in intervention group. Conclusion Both methods showed equal levels of knowledge acquisition and long‐term decline in NLS performances. Verbalisation in step 3 influenced speed of applied NLS performance

Serum cytokines MCP-1 and GCS-F as potential biomarkers in pediatric inflammatory bowel disease

Background Inflammatory bowel diseases (IBDs) with the subtypes ulcerative colitis (UC) and Crohn disease (CD), are chronic autoimmune inflammatory disorders of the gastrointestinal tract. Cytokines are associated with the development and progression in pediatric IBD. We measured cytokine levels in pediatric IBD patients to assess their potential function as biomarkers in disease assessment. Method In this prospective cohort study, we enrolled 33 children with IBD. All patients were in stable remission for 3 months on enrollment. Patients who developed a relapse within six months after enrollment were classified as relapsers. Blood sampling was performed at enrolment and for relapsers in relapse and post-relapse. Serum concentrations of 14 cytokines, chemokines and growth factors (IL-1α, IL-1β, IL-6, IL-12p40, IP-10, TNF-α, IFN-γ, IL-10, IL-8, MIP-1α, MCP-1, MCP-3, G-CSF, GM-CSF) were measured simultaneously using multiplex bead-based sandwich immunoassay on Luminex 100 system. Results MCP-1 was significantly higher in CD patients compared to UC patients at each disease stage: stable remission (P<0.048), unstable remission (P<0.013), relapse (P<0.026) and post-relapse (P<0.024). G-CSF was significantly increased in UC patients developing a relapse and in post-relapse stage compared to UC patients in remission (P<0.02 and p<0.03, respectively). Conclusion MCP-1 showed potential as a diagnostic biomarker in CD patients independent of disease activity as it was able to discriminate between subtypes of pediatric IBD. In UC patients, G-CSF was significantly elevated in relapsers indicating its use and role as a potential prognostic biomarker

Transiente Tachypnoe des Neugeborenen : sind Polymorphismen des Surfactantprotein B auslösend?

Die transiente Tachypnoe ist in der Regel eine selbstlimitierende Störung der pulmonalen Adaptation in der unmittelbaren neonatalen Periode des reifen Neugeborenen als Folge einer verzögerten Resorption der fetalen Lungenflüssigkeit. Unter den vier Surfactant-assoziierten Proteinen ist das lipophile SP-B das wichtigste Element des Surfactantsystems für die postnatale pulmonale Adaptation. Homozygote Träger der häufigsten Genvariation des SP-B Gens, der 121ins2-Mutation, versterben aufgrund des SP-B Mangels als Neugeborene an einer Form der kongenitalen alveolären Proteinose. Studien konnten zeigen, dass Polymorphismen im Intron 4 des SP-B zum Risiko und Verlauf des Atemnotsyndroms des Frühgeborenen assoziiert sind. Ziel unserer Arbeit war es, einen möglichen Zusammenhang zwischen genetischen Variationen des SP-B (heterozygote 121ins2-Mutation oder Polymorphismen im Intron 4) und der TTN zu untersuchen. Desweiteren sollte die Verteilung und der Aufbau der gefundenen Intron 4-Polymorphismen bestimmt werden und schließlich bereits publizierte Risikofaktoren der TTN anhand der eigenen klinischen Daten kritisch überprüft werden. Unser Patientenkollektiv erfasste 74 reife Neugeborene mit TTN und 83 gesunde als Kontrollgruppe. Neugeborene mit Infektionen, angeborenen kardialen oder pulmonalen Fehlbildungen, Asphyxie und Kinder diabetischer Mütter wurden ausgeschlossen. Zur Identifizierung der Intron 4-Polymorphismen und der heterozygoten 121ins2-Mutation aus EDTA-Blut oder Blutfilterkärtchen wurden PCR, Fragmentlängenanalysen und Gensequenzierungen durchgeführt. Beide Gruppen zeigten keinen statistischen Unterschied in der Verteilung des Gestationsalters (38 SSW vs. 39 SSW), Apgar-Score <7 nach 5 Minuten (beide 0%) und Nabelschnur pH < 7,10 (beide 0%). In der TTN-Gruppe war der Anteil an männlichen Neugeborenen (68,9% vs. 44,6%, p=0,004) und mit Sectio ceasarea entwickelten Neugeborenen (70,3% vs. 30,1%, p<0,001) signifikant höher. Das Geburtsgewicht der Neugeborenen mit TTN war im Vergleich zu ihren Kontrollen signifikant niedriger (3091g vs. 3325g, p=0,006). Der Anteil intrauterin wachstumsretardierter oder makrosomer Neugeborener zeigten keinen signifikanten Unterschied. Bei keinem der untersuchten Patienten fand sich die 121ins2-Mutation. Die Häufigkeit der Intron 4-Polymorphismen unterschied sich nicht zwischen erkrankten Kindern und der Kontrollgruppe (9,5% vs. 8,4%). Wir konnten bereits etablierte Risikofaktoren der TTN, wie männliches Geschlecht, niedriges Geburtsgewicht und Entwicklung per Sectio ceasarea, bestätigen. Intron 4-Polymorphismen und 121ins2-Mutation in den untersuchten Genabschnitten erklären nicht das Krankheitsbild der TTN. Weitere Untersuchungen sind zur Klärung der Ätiologie der transitorischen Tachypnoe notwendig.TTN is usually a benign self-limiting respiratory disorder in the immediate neonatal period. The lipophilic surfactant-associated protein B (SP-B) was demonstrated to be the most relevant structural component of the surfactant system for immediate postnatal pulmonary adaptation. Homozygous 121ins2 mutation of the SP-B encoding gene results in SP-B deficiency and fatal neonatal respiratory failure. Furthermore polymorphisms within the intron 4 of the SP-B gene were shown to be related to the risk and course of respiratory distress syndrome. We therefore aimed at investigating whether genetic variations of SP-B (heterozygous 121ins2 mutation or intron 4 polymorphisms) may be associated with TTN. An other goal of our research was to determine the distribution and structure of identified intron 4 polymorphisms. At least own clinical data will be discussed with previous published risk factors of the TTN. In order to identify SP-B heterozygous 121ins2 mutation and intron 4 polymorphisms, we analyzed genomic DNA by means of PCR amplification, fragment length and sequence analysis in 74 term neonates presenting with TTN and 83 healthy term infants as controls. Newborns with any infection, pulmonary or cardiac congenital malformations, postnatal asphyxia and infants born to diabetic mothers were excluded. Both groups showed no statistical difference in gestational age (39 weeks vs. 38 weeks), Apgar-score at 5 minutes < 7 (0% each) and umbilical artery pH < 7.10 (0% each). The frequency of male infants (68.9% vs. 44.6%, p=0.004) and neonates born via caesarean section (70.3% vs. 30.1%, p<0.001) were significantly higher in TTN group. The TTN newborns showed a significantly lower birth weight than their controls (3091g vs. 3325g, p=0.006). There was no statistical difference in the frequency of newborns with IUGR or makrosomia between both groups. None of the neonates were heterozygous for the 121ins2 SP-B mutation. The frequency of intron 4 variations did not differ between TTN newborns and healthy controls (9.5% vs. 8.4%). Our data suggest male gender, low birth weight and caesarean section to be risk factors for TTN which is in accordance with previous studies. We conclude polymorphisms of intron 4 and heterozygous 121ins2 mutation not to associated with TTN. Further investigation is needed to understand underlying mechanisms of TTN

Patterns of volatile organic compounds in excrements of preterm neonates

Background: As neonates are susceptible for many diseases, establishing noninvasive diagnostic methods is desirable. We hypothesized that volatile organic compounds (VOCs) could be successfully measured in diaper samples. Methods: We performed a feasibility study to investigate whether ambient airindependent headspace measurements of the VOC profiles of diapers from premature infants can be conducted using ion mobility spectrometer coupled with multi-capillary columns (B & S Analytik GmbH). Results: We analysed 39 diapers filled with stool (n = 10) or urine (n = 20) respectively, using empty diapers as a control (n = 9). A total of 158 different VOCs were identified, and we classified the content of the diapers (urine or stool) according to their VOC profiles with a significance level of p<0.05. Conclusions: We have developed a novel method to study headspace VOC profiles of biosamples using ion mobility spectrometry coupled with multi-capillary columns. Using this method, we have characterized the VOC profiles of stool and urine of preterm neonates. Future studies are warranted to characterize specific VOC profiles in infections and other diseases of the preterm neonate, thus establishing quick and noninvasive diagnostics in the routine care of the highly vulnerable preterm and term neonates

Serum cytokines MCP-1 and GCS-F as potential biomarkers in pediatric inflammatory bowel disease.

BackgroundInflammatory bowel diseases (IBDs) with the subtypes ulcerative colitis (UC) and Crohn disease (CD), are chronic autoimmune inflammatory disorders of the gastrointestinal tract. Cytokines are associated with the development and progression in pediatric IBD. We measured cytokine levels in pediatric IBD patients to assess their potential function as biomarkers in disease assessment.MethodIn this prospective cohort study, we enrolled 33 children with IBD. All patients were in stable remission for 3 months on enrollment. Patients who developed a relapse within six months after enrollment were classified as relapsers. Blood sampling was performed at enrolment and for relapsers in relapse and post-relapse. Serum concentrations of 14 cytokines, chemokines and growth factors (IL-1α, IL-1β, IL-6, IL-12p40, IP-10, TNF-α, IFN-γ, IL-10, IL-8, MIP-1α, MCP-1, MCP-3, G-CSF, GM-CSF) were measured simultaneously using multiplex bead-based sandwich immunoassay on Luminex 100 system.ResultsMCP-1 was significantly higher in CD patients compared to UC patients at each disease stage: stable remission (PConclusionMCP-1 showed potential as a diagnostic biomarker in CD patients independent of disease activity as it was able to discriminate between subtypes of pediatric IBD. In UC patients, G-CSF was significantly elevated in relapsers indicating its use and role as a potential prognostic biomarker

Serum vascular endothelial growth factor is a potential biomarker for acute mountain sickness

Background: Acute mountain sickness (AMS) is the most common disease caused by hypobaric hypoxia (HH) in high-altitude (HA) associated with high mortality when progressing to high-altitude pulmonary edema (HAPE) and/or high-altitude cerebral edema (HACE). There is evidence for a role of pro- and anti-inflammatory cytokines in development of AMS, but biological pathways and molecular mechanisms underlying AMS remain elusive. We aimed to measure changes in blood cytokine levels and their possible association with the development of AMS.Method: 15 healthy mountaineers were included into this prospective clinical trial. All participants underwent baseline normoxic testing with venous EDTA blood sampling at the Bangor University in United Kingdom (69 m). The participants started from Beni at an altitude of 869 m and trekked same routes in four groups the Dhaulagiri circuit in the Nepali Himalaya. Trekking a 14-day route, the mountaineers reached the final HA of 5,050 m at the Hidden Valley Base Camp (HVBC). Venous EDTA blood sampling was performed after active ascent to HA the following morning after arrival at 5,050 m (HVBC). A panel of 21 cytokines, chemokines and growth factors were assessed using Luminex system (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-1ra, sIL-2Rα, IFN-γ, TNF-α, MCP-1, MIP-1α, MIP-1β, IP-10, G-CSF, GM-CSF, EGF, FGF-2, VEGF, and TGF-β1).Results: There was a significant main effect for the gradual ascent from sea-level (SL) to HA on nearly all cytokines. Serum levels for TNF-α, sIL-2Rα, G-CSF, VEGF, EGF, TGF-β1, IL-8, MCP-1, MIP-1β, and IP-10 were significantly increased at HA compared to SL, whereas levels for IFN-γ and MIP-1α were significantly decreased. Serum VEGF was higher in AMS susceptible versus AMS resistant subjects (p &lt; 0.027, main effect of AMS) and increased after ascent to HA in both AMS groups (p &lt; 0.011, main effect of HA). Serum VEGF increased more from SL values in the AMS susceptible group than in the AMS resistant group (p &lt; 0.049, interaction effect).Conclusion: Cytokine concentrations are significantly altered in HA. Within short interval after ascent, cytokine concentrations in HH normalize to values at SL. VEGF is significantly increased in mountaineers suffering from AMS, indicating its potential role as a biomarker for AMS

Hydrops fetalis with isolated massive ascites in a preterm neonate with rhesus disease

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