Tissue Doppler imaging in very preterm infants during the first 24 h of life: an observational study.

BACKGROUND: Very preterm newborn infants often need cardiovascular support. More knowledge about myocardial function and factors that influence the immature myocardium may be helpful for optimising cardiovascular support in these infants. OBJECTIVE: Serial assessment of global myocardial function by means of colour tissue Doppler imaging (cTDI) in very and extremely preterm infants during the first 24 h of life. STUDY DESIGN: One-centre, prospective, observational longitudinal cohort study in a third level Neonatal Intensive Care Unit. Sixty-five infants with median (range) gestational age (GA) 27 (24-31) weeks and birth weight (BW) 1049 (484-1620) g underwent echocardiographic examinations including cTDI at 5, 12 and 24 h after birth. MAIN OUTCOME MEASURES: Peak systolic and peak diastolic annular velocity and peak annular displacement of the left and right ventricle. RESULTS: There was a significant reduction in systolic and diastolic velocities and displacement of both ventricles from 5 to 12 h age. From 12 to 24 h, there was a non-significant increase in myocardial velocities and displacement. At 5 h, babies with haemodynamically significant patent ductus arteriosus (PDA) had significantly higher systolic and diastolic velocities in both ventricles than those with non-significant PDA. CONCLUSIONS: Myocardial tissue velocities decrease significantly from 5 to 12 h after birth in very preterm infants. Further studies are needed to confirm these results and to determine their clinical implications.

Superior vena cava flow: feasibility and reliability of the off-line analyses.

BACKGROUND: Superior vena cava (SVC) flow has become a surrogate measure of systemic blood flow in neonates. OBJECTIVE: The aim of this study was to establish normal SVC flow values in healthy term infants the first 3 days of life and to evaluate the feasibility and reliability of the off-line analyses. DESIGN: Doppler echocardiography of SVC flow was performed in 48 healthy term infants the first 3 days of life. Off-line analyses were thereafter performed by one cardiologist to investigate the changes in SVC flow from day 1 to day 3 and to establish normal values. Intra- and inter-observer variability was analysed in a subset of 20 infants by three paediatric cardiologists. RESULTS: The authors found a decrease in mean SVC flow from 99 ml/kg/min at day 1 to 77 ml/kg/min at day 3. Reliable diameter images were obtained in 85% and velocity recordings in 81%. The mean variability of SVC flow was 17% in the intra-observer analysis and 29% in the inter-observer analysis. CONCLUSION: The main challenge of the method is the measurement of SVC diameter. The same observer should ideally perform sequential analyses. Special caution should be taken when making clinical implications from non-optimal pictures.

The outcome in newborns with congenital diaphragmatic hernia in a Norwegian region.

AIM: To evaluate the therapeutic strategies used in neonates with congenital diaphragmatic hernia (CDH) during the last 15 years in our department. METHOD: A retrospective study of 27 neonates with CDH treated at the Neonatal Intensive Care Unit at Ullevaal University Hospital between 1992 and 2006. Since 1992 we have used delayed operative repair and high-frequency ventilation (HFV). Because surfactant replacement and inhaled nitric oxide (iNO) therapy have been used since 1997, we divided the patients into two groups; group 1 from 1992 to 1996 (9 patients) and group 2 from 1997 to 2006 (18 patients). RESULTS: The overall survival was 70%. Group 1 had an exceptionally good outcome, 100% survival versus 56% in the last group. CONCLUSION: Pulmonary hypoplasia and pulmonary hypertension are still the most challenging factors in treatment of neonates with CDH, despite novel therapeutic modalities, such as HFV, surfactant and iNO. Delayed surgery in CDH allows pre-operative stabilization. Extracorporeal membrane oxygenation must be considered in the most severe cases.

Analysis of the apoptotic and therapeutic activities of histone deacetylase inhibitors by using a mouse model of B cell lymphoma.

Histone deacetylase inhibitors (HDACi) can elicit a range of biological responses that affect tumor growth and survival, including inhibition of cell cycle progression, induction of tumor cell-selective apoptosis, suppression of angiogenesis, and modulation of immune responses, and show promising activity against hematological malignancies in clinical trials. Using the Emu-myc model of B cell lymphoma, we screened tumors with defined genetic alterations in apoptotic pathways for therapeutic responsiveness to the HDACi vorinostat. We demonstrated a direct correlation between induction of tumor cell apoptosis in vivo and therapeutic efficacy. Vorinostat did not require p53 activity or a functional death receptor pathway to kill Emu-myc lymphomas and mediate a therapeutic response but depended on activation of the intrinsic apoptotic pathway with the proapoptotic BH3-only proteins Bid and Bim playing an important role. Our studies provide important information regarding the mechanisms of action of HDACi that have broad implications regarding stratification of patients receiving HDACi therapy alone or in combination with other anticancer agents.

Localization and physical property experiments conducted by Opportunity at Meridiani Planum.

The location of the Opportunity landing site was determined to better than 10-m absolute accuracy from analyses of radio tracking data. We determined Rover locations during traverses with an error as small as several centimeters using engineering telemetry and overlapping images. Topographic profiles generated from rover data show that the plains are very smooth from meter- to centimeter-length scales, consistent with analyses of orbital observations. Solar cell output decreased because of the deposition of airborne dust on the panels. The lack of dust-covered surfaces on Meridiani Planum indicates that high velocity winds must remove this material on a continuing basis. The low mechanical strength of the evaporitic rocks as determined from grinding experiments, and the abundance of coarse-grained surface particles argue for differential erosion of Meridiani Planum.

Importance of ets1 proto-oncogene for breast cancer progression.

Ets proteins are transcription factors, which share a unique DNA binding domain, the Ets domain. Some members of the Ets family are implicated in tumorigenesis. Ets1, the founder of the Ets family, is predominantly expressed in invasive tumors and able to activate certain genes encoding ECM-degrading proteases. We used RNA-interference in combination with DNA chip analysis to identify Ets1-regulated genes in MDA-MB-231 breast cancer cells. Of the Ets1-responsive proteases, matrix metalloproteases MMP1 and MMP9, but not MMP3 or uPA, showed reduced RNA levels when endogenous Ets1 expression was suppressed. These data suggest that Ets1 regulates only a certain subset of ECM-degrading proteases. How Ets1 is regulated in invasive breast cancer cells is unknown. The observations that protein kinase C inhibitors abrogated Ets1 expression and that protein kinase C was able to increase Ets1-dependent transcription imply that protein kinase C is a potential regulator of Ets1 activity in breast cancer cells.

Characteristics of breast milk and serology of women donating breast milk to a milk bank.

OBJECTIVE: Breast milk is the most important nutrient to all newborn babies. If the mother's milk production is insufficient, it is important to provide donor breast milk without reduction of its immunologic and antimicrobial properties. Early use of breast milk to preterm infants has shown a reduced incidence of necrotising enterocolitis, a faster tolerance of enteral feeding, and a reduced need of parenteral nutrition. It is important to have milk from a CMV-IgG negative donor to VLBW infants considered immunocompromised. METHODS: Between January 1st and December 31st 2001, 69 women delivered 1.973 litres (mean 28.6 litres/woman/year). 73% had college education, were primipara, and with a mean age of 30.7 years. Those who smoked, used alcohol or any medications were refused as donors. They started to deliver approximately 7 weeks after having given birth and continued for a mean of 4 months. Each milk sample was tested for bacterial growth. Every donor was screened for HIV, CMV-IgG and hepatitis B/C before donating milk and thereafter every third month. RESULTS: 62.3% was CMV-IgG positive. Samples containing staphylococcus aureus, klebsialla-, enterobacter- and serratia-species or E. coli, and all samples containing > 10(4) cfu/ml were pasteurised. Overall, only 10.5% of the samples were pasteurised. CONCLUSION: It is possible and important to provide VLBW babies with fresh frozen unpasteurised CMV-IgG negative breast milk until their own mothers' milk production is sufficient.

Localization and physical properties experiments conducted by Spirit at Gusev Crater.

The precise location and relative elevation of Spirit during its traverses from the Columbia Memorial station to Bonneville crater were determined with bundle-adjusted retrievals from rover wheel turns, suspension and tilt angles, and overlapping images. Physical properties experiments show a decrease of 0.2% per Mars solar day in solar cell output resulting from deposition of airborne dust, cohesive soil-like deposits in plains and hollows, bright and dark rock coatings, and relatively weak volcanic rocks of basaltic composition. Volcanic, impact, aeolian, and water-related processes produced the encountered landforms and materials.

Spread of methicillin-resistant Staphylococcus aureus in a neonatal intensive unit associated with understaffing, overcrowding and mixing of patients.

Over the period May-June 1999, an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) was registered in eight newborns in a neonatal intensive care unit (NICU) at the Department of Pediatrics, Ullevål University Hospital (UUH) in Oslo. Seven were infected or colonized with an indistinguishable strain, detected at the NICU, and one patient with a slightly different PFGE type (i.e. a subtype) was registered at the outpatient clinic. The MRSA strains resembled the sensitive, inbred 'Norwegian type' described four years earlier at UUH, showing a relatively low and heterogenic methicillin resistance (MIC 12-96 mg/L), and susceptibility to most other anti-staphylococcal agents. Before and during the outbreak, there was high activity, understaffing, overcrowding and a mix of patients; 42% of the staff were relatively untrained, and up to 62% (during weekends) were extra nursing staff, partly from other Scandinavian countries. All cases were isolated (air and contact isolation), and all other patients and personnel were treated as being exposed to MRSA (isolated from other departments) until the last patient had been identified, disinfection of all rooms was complete, and all screening samples from staff and other patients were negative. The NICU and the delivery suite were closed for one week for disinfection and screening. The outbreak ended after 34 days. Since then, two years later, no further cases have been detected in the NICU or the delivery suite.

Perfluorochemical liquids do not stimulate endothelin-1 or nitric oxide production in human blood leukocytes.

The purpose of these studies was to examine if perfluorochemical (PFC) liquids stimulate blood leukocytes to secrete nitric oxide (NO) and/or endothelin-1 (ET-1). As such, NO and ET-1 may modulate broncho- and vascular dilatation and constriction, respectively, and thereby influence the clinical condition of a patient in respiratory distress with persistent pulmonary hypertension. Blood leukocytes in their natural habitat (whole blood) were incubated in the presence of two different perfluorochemicals (perflubron and perfluorodecalin). The overall response in ET-1 or NO (indirectly measured as nitrite/nitrate) production was examined at increasing PFC percentages (wt/vol) of PFC/whole blood. The lowest proportion used, 0.001% (wt/vol), was relevant to serum concentrations of PFC observed in liquid-ventilated individuals, whereas the highest proportion PFC, 50% (wt/vol), would mimic a situation where leukocytes are presented to PFC-filled airways. Plasma levels of freshly drawn blood, similar to levels of incubated (6 h) non-PFC-supplemented cultures, were ET-1 0.59 +/- 0.07 pg/ml (6 h, mean +/- SEM) and NO(-2)/NO(-3) 50 +/- 9 microM (6 h). Perflubron or perfluorodecalin did not induce significant differences in ET-1 or NO(-2)/NO(-3) levels as function of PFC type or dose. In conclusion, PFC liquids do not stimulate production in leukocytes in vitro of substances that may modulate constriction or dilatation in the vascular and respiratory tract systems.

A comparison of changes in dental students' and medical students' approaches to learning during professional training.

The purposes of this study were 1) to compare the learning approaches of dental students (DS) and medical students (MS) for the Class of 1998 at a single institution at admission and graduation and 2) to determine if their learning approaches changed over the course of their studies. An Approaches to Studying Inventory (ASI) was administered to DS and MS at two times: their first month in school and their last month in school. Means and standard deviations were calculated for three ASI orientations to studying: 'Meaning', 'Reproducing', and 'Achieving'. An additional domain referred to as 'Styles and Pathologies' identified learning problems. In comparison, DS and MS demonstrated a different pattern of learning approaches at matriculation; however, at graduation these differences were less apparent. Over time, DS reported a decreased use, and MS reported an increased use of the Reproducing orientation bringing them closer together. MS also demonstrated an increased use of the Achieving orientation. The Meaning orientation, which indicates a deep approach to learning, was equivalently used by both groups at entry and remained unaltered.

Transforming growth factor beta regulates parathyroid hormone-related protein expression in MDA-MB-231 breast cancer cells through a novel Smad/Ets synergism.

The majority of breast cancers metastasizing to bone secrete parathyroid hormone-related protein (PTHrP). PTHrP induces local osteolysis that leads to activation of bone matrix-borne transforming growth factor beta (TGF beta). In turn, TGF beta stimulates PTHrP expression and, thereby, accelerates bone destruction. We studied the mechanism by which TGF beta activates PTHrP in invasive MDA-MB-231 breast cancer cells. We demonstrate that TGF beta 1 up-regulates specifically the level of PTHrP P3 promoter-derived RNA in an actinomycin D-sensitive fashion. Transient transfection studies revealed that TGF beta 1 and its effector Smad3 are able to activate the P3 promoter. This effect depended upon an AGAC box and a previously described Ets binding site. Addition of Ets1 greatly enhanced the Smad3/TGF beta-mediated activation. Ets2 had also some effect, whereas other Ets proteins, Elf-1, Ese-1, and Erf-1, failed to cooperate with Smad3. In comparison, Ets1 did not increase Smad3/TGF beta-induced stimulation of the TGF beta-responsive plasminogen activator inhibitor 1 (PAI-1) promoter. Smad3 and Smad4 were able to specifically interact with the PTHrP P3-AGAC box and to bind to the P3 promoter together with Ets1. Inhibition of endogenous Ets1 expression by calphostin C abrogated TGF beta-induced up-regulation of the P3 transcript, whereas it did not affect the TGF beta effect on PAI expression. In TGF beta receptor II- and Ets1-deficient, noninvasive MCF-7 breast cancer cells, TGF beta 1 neither influenced endogenous PTHrP expression nor stimulated the PTHrP P3 promoter. These data suggest that TGF beta activates PTHrP expression by specifically up-regulating transcription from the PTHrP P3 promoter through a novel Smad3/Ets1 synergism.

Perfluorochemical liquids modulate cell-mediated inflammatory responses.

OBJECTIVE: To examine whether chemically different perfluorochemical liquids (PFC) (perfluorodecalin [PFD]; perflubron [PFB]) induce inflammatory responses in blood leukocytes. SETTING: University research laboratory. DESIGN: Whole blood from 12 healthy adults was incubated with increasing PFC concentrations and/or bacterial lipopolysaccharide. MEASUREMENTS AND MAIN RESULTS: Adhesion molecules (CD62L, CD11b), reactive oxygen species, and cytokine responses in resting and activated leukocyte subtypes were studied. Scanning and transmission electron microscopies were performed. At the highest concentrations, PFB stimulated a significant increase in resting monocytic reactive oxygen species production; all types of blood leukocytes were unresponsive to PFD. Neither PFB nor PFD changed CD62L expression; PFB increased CD11b expression in monocytes and granulocytes. PFD induced a small though significant increase in interleukin-8 secretion. When simulating a condition in which patients with severe lung disease or sepsis would be ventilated with PFC, neither PFB nor PFD plus lipopolysaccharide stimulated tumor necrosis-alpha or interleukin-8 production above levels induced by lipopolysaccharide alone, but rather demonstrated a trend for decreased tumor necrosis factor-alpha production. Expression of CD11b and CD62L and the production of reactive oxygen species were not changed beyond the levels induced by lipopolysaccharide alone. As a morphologic correlate to the above proinflammatory changes, surface-bound blebs and intracellular vacuoles were seen by electron microscopy. CONCLUSIONS: At PFC concentrations comparable with those in blood during liquid ventilation, PFC liquids did not induce variables associated with inflammation. In the presence of high PFC concentrations, simulating the condition in which bronchoalveolar cells are exposed to PFC, monocytes may be induced by PFB to produce reactive oxygen species, and blood leukocytes induced by PFB to express CD11b and by PFD to secrete interleukin-8; the presence of either PFC attenuated tumor necrosis factor-alpha production after lipopolysaccharide stimulation.

[Prediction of IQ among children with birth weight under 1, 501 gms]. / Prediksjon av IQ hos barn med fødselsvekt under 1,501 gram.

INTRODUCTION: As a group, preterm infants are at considerable risk of cognitive difficulties. However, predicting cognitive sequelae has proved to be difficult. The current study reports on prediction of IQ at age eight years on the basis of the children's perinatal and developmental status, as well as parental socioeconomic status. MATERIALS AND METHODS: The sample consisted of 104 infants with birth weight < or = 1,501 g (53 girls), recruited consecutively in the neonatal intensive care unit and followed up to age eight years. Perinatal status, early cognitive development, and parental socioeconomic status served as predictors. Cognitive ability assessed on two commonly used intelligence tests served as outcome. The participants did not represent a total population, and no control group was used. RESULTS: Regression analyses revealed that birth weight, the Bayley cognitive index at 39 and 56 weeks, and parental socioeconomic status all made significant and independent contributions to outcome. Though the Bayley index made no significant contribution at age 29 weeks, it was the only variable at age two that was related to IQ at age eight. INTERPRETATION: Perinatal data are generally of limited value for the prediction of later IQ among preterm infants. However, when combined with information about parental socioeconomic status and the infants' developmental status up to age 56 weeks, birth weight made a unique and significant contribution as a predictor of later IQ. At age two years the cognitive status of prematurely born children was sufficiently consolidated to yield a valid prediction of outcome.

Spectrum of outcome in infants with extreme neonatal jaundice.

UNLABELLED: The increasing number of case reports on neurologic sequelae related to hyperbilirubinaemia may represent a re-emergence of kernicterus in the industrialized world. However, not much has been written about infants who survived extreme levels of serum bilirubin without neurologic damage. We present three cases of extreme neonatal hyperbilirubinaemia, all with peak serum bilirubin levels >600 micromol/L. Two of the infants developed neurologic sequelae, but the third infant did not. In contrast to the two with sequelae, the infant without sequelae was female, had a positive Coombs' test, less clinical signs compatible with bilirubin encephalopathy, and a shorter exposure to serum bilirubin values >400 micromol/L. CONCLUSION: The basic mechanism of bilirubin neurotoxicity remains unknown, and it is not clear why some infants do not develop neurologic injury at serum bilirubin levels at which others do. We speculate that a comparison between patients with sequelae and those without may yield important information.

Neonatal withdrawal syndrome after in utero exposure to selective serotonin reuptake inhibitors.

UNLABELLED: Selective serotonin reuptake inhibitors (SSRIs) are a new group of antidepressants used in mild to moderate cases of depression. In studies evaluating the safety of SSRIs during pregnancy, no increase in major anomalies has been reported. This might have led to increasing off-label prescription of SSRIs to pregnant women. Neonatal withdrawal syndrome commonly occurs in infants exposed during the third trimester to drugs known to cause addiction. We report five cases of neonatal withdrawal syndrome after third trimester in utero SSRI exposure. In three cases the mother used paroxetine in doses from 10 to 40 mg, one mother used citalopram 30 mg, and one mother fluoxetine 20 mg. Withdrawal symptoms occurred within few days after birth and lasted up to one month after birth. Four of the infants needed treatment with chlorpromazine. Symptoms were irritability, constant crying, shivering, increased tonus, eating and sleeping difficulties and convulsions. CONCLUSION: Neonatal withdrawal syndrome can occur after third trimester in utero SSRI exposure. Further research should focus on whether it is safe to use SSRIs during the last trimester. All neonates exposed to SSRIs during the last trimester should be followed-up closely for withdrawal symptoms after birth.

Patent ductus venosus does not lead to alimentary galactosaemia in preterm infants.

UNLABELLED: The aim of this study was to investigate if an open ductus venosus representing a portal-caval shunt can lead to transient "alimentary galactosaemia" in preterm infants fed human breast milk. Twenty-six preterm infants (28-34 wk of gestational age) with open ductus venosus were included. Capillary blood samples for measurement of galactose and glucose were collected before, 30 and 50 min after a meal with breast milk (range 12-23 mL/kg). Ultrasound studies of the blood flow in the ductus venosus, truncus coeliacus, superior mesenteric artery and left hepatic vein were performed before and 30 min after the meal. There was a significant rise in blood glucose after 30 and 50 min, indicating a sufficient lactose load. Galactose, however, was either not detectable or was just above the detectable limit (0.1-0.4 mmol/L), with no changes after the meal. An increased flow velocity was found in the ductus venosus and superior mesenteric artery after 30 min (p < or = 0.001) indicating increased entero-hepatic and portal-caval shunting. CONCLUSION: A patent ductus venosus does not lead to a significant hypergalactosaemia in preterm infants fed human breast milk. Thus, in respect to breast-milk feeding, this is regarded safe in healthy preterm infants even with an open ductus venosus. The increased portal-caval shunting may, however, influence the hepatic metabolism of other enterally absorbed substances.

[Psychological status at 8-9 years of age in children with birth weight below 1,501 grams]. / Psykologisk status ved 8-9 års alder hos barn med fødselsvekt under 1,501 gram.

BACKGROUND: Studies have demonstrated that many children with low birth weight show signs of developmental disorders. Research and clinical experience indicate that gestational age is related to outcome. The aim of the present study was to investigate the differential outcome of children with gestational age < or = 28 weeks and those who were born later. MATERIAL AND METHODS: The sample consisted of 104 infants with birth weight < or = 1,500 g (53 girls) who were followed up to age eight years, with subsequent testing of school-related achievement at age nine years. Well-known instruments to identify developmental disorders and learning difficulties were used. RESULTS: The results showed that for the sample as a whole, AD/HD was the most prevalent disorder. There was a moderate degree of delay in intellectual development and of learning difficulties. In these areas there were significant differences in outcome in favour of the group with gestational age > 28 weeks. No significant sex differences were found, except in relation to mathematical skills, where boys performed better than girls. INTERPRETATION: As a group the children with very low birth weight had adequate intellectual and scholastic outcome. However, the prevalence of AD/HD was relatively high (27%). Low gestational age, but not dysmaturity, was associated with increased risk for poorer outcome.