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Contains fulltext : 170277.pdf (publisher's version ) (Open Access)

Contains fulltext : 170277.pdf (publisher's version ) (Open Access)

Contains fulltext : 170277.pdf (publisher's version ) (Open Access)

BACKGROUND: In very preterm infants, clinical decision-making, such as closing a patent ductus arteriosus (PDA), may be aided by measuring circulating natriuretic and endothelial pro-peptides. OBJECTIVES: To investigate the association between perinatal characteristics, PDA echocardiography and plasma concentrations of stable pro-peptides of B-type natriuretic peptide (NT-proBNP), atrial natriuretic peptide (MR-proANP) and endothelin-1 (CT-proET-1). METHODS: A prospective, cross-sectional, single-center study was performed in 66 infants who were less than 32 weeks of gestational age. Pro-peptide concentrations were determined at birth and at day 2-3 of life. RESULTS: Plasma concentrations of all 3 pro-peptides increased on average 2- to 5-fold from birth to day 2-3 of life. NT-proBNP and MR-proANP were closely related at birth and at day 2-3 (Rs 0.902 and 0.897, respectively, p < 0.001), whereas CT-proET-1 was related to NT-proBNP and MR-proANP at birth (Rs 0.478 and 0.460, respectively, p < 0.001) but not at day 2-3. Birth weight was negatively related to all 3 pro-peptides at birth (p < 0.01); however, preeclampsia and compromised placental perfusion were associated with elevated NT-proBNP and MR-proANP concentrations at birth. At day 2-3, MR-proANP and NT-proBNP correlated significantly with the ductal diameter (Rs 0.416 and 0.415, respectively, both p = 0.011), whereas CT-proET-1 correlated with the left atrium/aorta ratio (Rs 0.506, p = 0.027). CT-proET-1 was elevated in infants with treated compared to untreated PDA [median (5-95% range) 388 (272-723) vs. 303 (152-422) pmol/l, p = 0.011], but not NT-proBNP or MR-proANP. CONCLUSION: CT-proET-1 is a promising predictor in determining the need for PDA intervention.

For many years, oxytocin has been viewed as the primary hormone edging endocrinology, behavior, and pain in mothers and infants around parturition. Very recent work puts the vasopressin receptor 1A in the focus of peripheral analgesia and pain relief in respect to circulating vasopressin and oxytocin. Here, we present a concise overview on these new findings, will discuss them in context of parturition, and will outline new avenues.

QUESTION UNDER STUDY: The study has following objectives: 1) to determine the incidence of higher-order multiple births from 2005 to 2008 in Switzerland and its evolution over the last twenty years, and 2) to analyse the neonatal outcome and its change over the last two decades. METHODS: Data on higher-order multiple births were retrospectively obtained from Swiss obstetric and neonatal hospitals and compared with results from the first two national surveys. RESULTS: The incidence of higher-order multiple births was 35.3/100,000 live births for triplets, 0.7/100,000 for quadruplets and 0.3/100,000 for quintuplets. All newborns were premature with a median gestational age of 32 1/7 weeks for triplets, 29 2/7 weeks for quadruplets and 28 4/7 weeks for quintuplets. 94% of triplets and all quadruplets and quintuplets survived the neonatal period. Over the last two decades, the incidence of quadruplet and quintuplet births has fallen, while that of triplet births has risen by 40%. The perinatal mortality of triplets has decreased and the neonatal morbidity, mainly respiratory distress, has remained constant. CONCLUSION: Higher-order multiple births have a high morbidity that has not improved over the last two decades. The incidence of higher-order multiple births is still increasing, which demonstrates that reproductive medicine in Switzerland is not yet sufficiently controlled and monitored.

Die Entlassung des Neugeborenen aus dem Spital markiert die Schnittstelle zwischen Spital und Kinderarzt. Es ist der Augenblick, in dem die Verantwortung den Eltern und den ambulanten Betreuungsstrukturen übergeben wird, möglichst zeitnah und präzise dokumentiert in der Epikrise an den niedergelassenen Kinderarzt. Zentraler Bestandteil ist die Vorbereitung und umfassende Information der Eltern vor der Entlassung aus dem Spital. Der erste Besuch beim weiterbetreuenden Kinderarzt sollte 2 Wochen nach Spitalaustritt erfolgen.

Hypoxia is a reduction in the normal level of tissue oxygen tension, which occurs in human living at high altitude, during embryonic and fetal development and commonly in a variety of acute and chronic vascular, pulmonary, and neoplastic diseases. The identification of the master transcriptional regulator in response to hypoxia (hypoxia inducible factor-1, HIF-1) and the revelation of the molecular oxygen sensing mechanisms by prolyl hydroxylases domain (PHD) proteins expanded immensely the understanding of the cellular response to hypoxia. Based on our observation that HIF-1 signaling occurs in the leukemic bone marrow of childhood acute lymphoblastic leukemia (ALL), this PhD-thesis focuses on the identification of new oxygen regulated target genes either involving HIF-1 (Histone demethylase Jumonji domain containing 1A, JMJD1A, and Wilms’ tumor suppressor 1, Wt1) or alternative mechanisms (RNA binding motif protein 3, RBM3, and cold inducible RNA-binding protein, CIRP). We characterize the function of these HIF-1 dependent and independent target genes in respect to cellular adaptation to hypoxia, their tissue specific role, and their implications in diseases. The studies presented here have contributed 1) to a deeper and better understanding of the adaptation of leukemic cells to the bone marrow microenvironment, 2) to the identification of genes involved in epigenetic processes (JMJD1A) and cell survival (WT1) in response to decreased oxygen tension mediated by HIF-1, 3) to the identification of genes (RBM3 and CIRP), which are up-regulated by decreased oxygen tension via an alternative signaling mechanism not involving the master transcriptional regulator in response to hypoxia, and 4) to the characterization of RBM3 as a new survival protein protecting cells from adverse growth conditions such as serum deprivation-induced cell death.