bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancement of Surfactant Effect by a Mechanical Volume Recruitment Maneuver Depends on the Lungs Preexisting Distension
Authors: Krause Martin F. , Hoehn Thomas 
Published: April 2003

‘Rescue’ surfactant treatment of premature infants with respiratory distress syndrome (RDS) results in two mechanisms: stabilization of alveoli already being ventilated and recruitment of alveoli collapsed before surfactant administration. Mechanical recruitment of alveoli from this collapsed compartment might enhance the immediate effects of surfactant treatment. To test this hypothesis 15 mechanically ventilated young rabbits underwent repeated airway lavage with normal saline at a constant, positive end-expiratory pressure (PEEP) of 3 cm H<sub>2</sub>O until both the a/A ratio was <0.12 and a peak inspiratory pressure (PIP) >20 mbar was needed to keep the tidal volume (V<sub>T</sub>) at 10 ml/kg. Surfactant (Survanta<sup>®</sup>) was given over 4 min in conjunction with a mechanical volume recruitment maneuver (VRM) which consisted of an increased PIP by 33% of baseline values. The effects of surfactant were assessed using two indices of gas exchange (a/A ratio and PaCO<sub>2</sub>), four indices of lung function (functional residual capacity, FRC, dynamic lung compliance, C<sub>rs</sub>, V<sub>T</sub> and the alveolar portion of V<sub>T</sub>) and postmortem pressure-volume curves and were compared with two groups of rabbits receiving surfactant alone or no surfactant at all. VRM yielded an increase in C<sub>rs</sub> by +22% whereas V<sub>T</sub> increased by +58% suggesting overdistension of terminal airways to some extent. There were no differences between the surfactant and the VRM+surfactant groups for all indices assessed after an observational period of 2 h following surfactant administration. In a previous model using a PEEP of 1 cm H<sub>2</sub>O [Krause et al., Am J Respir Crit Care Med 1997;156:862–866], significant differences have been disclosed for C<sub>rs</sub>, V<sub>T</sub> and FRC. In conclusion, the enhancement of surfactant effect by VRM largely depends on the preexisting distension of the lungs.
Newborn Tissue Concentrations of Bupivacaine following Maternal Epidural Administration during Labor in Guinea Pigs
Authors: Golub Mari S. , Kaaekuahiwi Margaret A. , Eisele Pamela H. , Zhang Hongjian , Jones A. Daniel , Eisele Jr. John H. 
Published: April 2003

Newborn plasma concentrations of maternally administered bupivacaine are often measured, but it is unclear how well they reflect tissue concentrations. Bupivacaine (0.25%) was administered epidurally (0.12 ml/kg) 10 min prior to labor induction in 6 term-pregnant guinea pigs. Plasma, brain, heart and liver samples were obtained for bupivacaine analysis from newborns (n = 22) after spontaneous delivery. Liver bupivacaine concentrations were 2–3 times greater than those in the plasma, brain, and heart. A similar pattern of tissue concentrations was seen in a smaller number of newborns delivered by cesarean section. Liver bupivacaine concentration decreased with drug-delivery interval in littermates, while heart and brain concentrations showed no relationship with drug-delivery interval. Blood gases of newborns reflected acidosis, which may have influenced tissue drug concentrations. Under conditions of the study, bupivacaine concentrations in heart and brain, potential sites of bupivacaine action, were lower than those observed in a peripheral blood sample.
Decreasing Reticulocyte Counts Associated with Declining Post-Dose Erythropoietin Plasma Levels in Anaemia of Prematurity
Authors: Meister Bernhard , Khoss August , Burda Gudrun , Bock Wolfgang , Kolmer Micha , Lischka Andreas , Pollak Arnold 
Published: April 2003

A prospective sequential, multicentre trial was conducted to determine the association between erythropoietin (EPO) plasma levels and the erythropoietic response to recombinant human erythropoietin (r-HuEPO) during long-term treatment of premature infants. Twenty-nine infants, gestational ages 26–34 weeks and postnatal ages more than 14 days, received 600 IU r-HuEPO per kg per week divided into three doses subcutaneously for haemoglobin levels less than 120 g/l or haematocrit less than 36% over a period of 4 weeks. Eight additional patients were studied for a total of 10 weeks. EPO plasma concentrations and haematologic parameters were measured prior to the onset of treatment and at 2-weekly intervals thereafter. Treatment with r-HuEPO resulted in a median increase in corrected reticulocyte counts of 2.5% (range 0.2–4.6%) above patient’s baseline, thereafter a decrease was observed. In the 8 patients followed for 10 weeks reticulocyte counts declined significantly during weeks 6–10 when compared with the first 4 weeks (p < 0.005). Median 72-hour post-dose EPO plasma levels increased significantly (p < 0.0001) to 57.3 mU/ml (range 5.0–160) above patient’s baseline after the first injection, but declined progressively thereafter until they approached baseline values at week 10. <b>Conclusion:</b> R-HuEPO treatment after the first month was associated with a decrease in post-injection plasma levels and a decrease in erythropoietic response. This decrease in erythropoietin’s efficacy and the decline observed in post-dose EPO plasma levels may be causally related.
Differential Development of Type 1 and Type 2 Cytokines and β-Chemokines in the Ontogeny of Healthy Newborns
Authors: Vigano Alessandra , Esposito Susanna , Arienti Donatella , Zagliani Arianna , Massironi Emilia , Principi Nicola , Clerici Mario 
Published: April 2003

Interleukin (IL)-2, interferon gamma (IFN-γ; type 1 cytokines), IL-4, and IL-10 (type 2 cytokines), and β-chemokines (MIP-1α and RANTES) production by cord blood lymphocytes (CBL) and peripheral blood lymphocytes (PBL) of newborns was analyzed in a cross-sectional study to examine the maturation of these components of the immune response. Immunophenotyping was performed on the same specimens. Results showed that the CD4/CD8 ratio remains stable, the percentage of natural killer cells decreases, and the number and percentage of B cells increase after birth. Analysis of cytokine production suggested that the production of all cytokines increases gradually and steadily after birth, and that IFN-γ and IL-10 production is reduced at birth whereas IL-2 and IL-4 production is not. Finally, mitogen-stimulated β-chemokine production was present at birth and increased slightly but significantly with age. These data indicate that a differential functional maturation of immune response after birth favoring a more precocious development of IL-2 (a type 1 cytokine) is present and should help to analyze the ontogeny of the immune system.
Effects of Dexamethasone on IL-1β, IL-6, and TNF-α Production by Mononuclear Cells of Newborns and Adults
Authors: Bessler H. , Mendel C. , Straussberg R. , Gurary N. , Aloni D. , Sirota L. 
Published: April 2003

The effects of dexamethasone on the production of interleukin (IL) 1β, IL-6, and tumor necrosis factor alpha were studied in preterm newborns, term infants, and adults. Twenty preterm and 22 term newborns and 30 healthy adults were included in the study. Mononuclear cells (MC) isolated from cord blood of newborns and peripheral blood of adults were incubated without or with lipopolysaccharide in the absence or presence of dexamethasone at concentrations between 10<sup>–8</sup> and 10<sup>–5</sup> M. The cytokine concentration in the supernatants was tested using enzyme-linked immunosorbent assay kits. Although a dose-dependent inhibition of the cytokine production was observed at pharmacological doses of dexamethasone in individuals of the three groups, differences in the intensity of the effect were observed between the groups. Spontaneous secretion of IL-1β or IL-6 by MC of preterm neonates was less inhibited by dexamethasone as compared with cells from adults. In contrast, the inhibitory effect of the drug on lipopolysaccharide-induced IL-6 and tumor necrosis factor alpha production was more pronounced on neonatal cells. As for term newborns, MC were more sensitive to the inhibitory effect of the drug on LPS-induced IL-6 production than cells of adults. The results suggest that dexamethasone treatment of preterm newborns may affect cytokine production with a consequent modulation of the host’s immune response.
Leukocyte Counts in Relation to the Method of Delivery during the First Five Days of Life
Authors: Chirico Gaetano , Gasparoni Antonella , Ciardelli Laura , Martinotti Lucia , Rondini Giorgio 
Published: April 2003

The goal of the present study was to evaluate total and differential leukocyte counts during the first 5 days of life in relation to the method of delivery. We included 203 healthy term infants; of these, 114 were born by vaginal delivery, and 89 by elective cesarean section. Total and differential leukocyte counts were evaluated at the following intervals: 0–6, 7–12, 13–24, 25–48, 49–72, 73–96, and 97–120 h after birth. The cord serum cortisol level was measured as an indicator of the degree of delivery-related stress. Mean leukocyte and neutrophil counts were higher in infants born by vaginal delivery in cord blood and up to 12 h of life. No significant differences were observed in the immature: total neutrophil ratios between the two groups of infants. The cord serum cortisol level was higher in vaginally delivered infants. A significant correlation was found between cortisol and leukocyte, neutrophil, or lymphocyte counts. The method of delivery produces significantly different total leukocyte and neutrophil counts during the first 12 h after birth; after this time, there appears to be no more variation of leukocyte counts during the first 5 days of life.
Stimulation of Fetal Granulopoiesis by Intrauterine Injection of Recombinant Human Granulocyte Colony- Stimulating Factor into Rat Fetuses
Authors: Fukumasu Yasuko , Fukumasu Hiroshi , Yamamasu Seiichi , Tachibana Daisuke , Imanaka Motoharu , Ogita Sachio 
Published: April 2003

The small neutrophil reserve and exaggerated release of stored neutrophils are factors which predispose neonates to neutrophil reserve exhaustion during bacterial sepsis. Our objective is to try to improve in utero the myelopoietic function of the fetus before delivery. In the first series, recombinant human (rh) granulocyte colony-stimulating factor (G-CSF) (rhG-CSF; 100 μg/kg) was injected subcutaneously into rat fetuses at the indicated times to assess drug absorption and fetal response. In the second series, rhG-CSF (100 μg/kg) or saline (control) was injected into the fetuses once every other day to investigate the effect of repeated injections of rhG-CSF on enhancing fetal myelopoiesis preceding birth. Delivery was performed by cesarean section on embryonic day 21. The plasma concentration of G-CSF was determined by ELISA. The effect of rhG-CSF injection on granulopoiesis was assessed by measurement of the neutrophil count in the fetal peripheral blood and by histological examination of the fetal bone marrow, spleen, and liver. Fetally administered rhG-CSF enhanced fetal myelopoiesis preceding birth.
Labeled Trimethyllysine Load Depletes Unlabeled Carnitine in Premature Infants without Evidence of Incorporation
Authors: Melegh B. , Tóth G. , Adamovich K. , Szekely G. , Gage D.A. , Bieber L.L. 
Published: April 2003

6-N-Trimethyl-[d<sub>9</sub>]-<i>L</i>-lysine (dTML), the labeled form of a mammalian carnitine precursor, was administered to two groups of premature infants. Although the urinary output of dTML significantly increased in the low-dose-treated group (100 μmol/day), this amount did not affect the urinary output or plasma levels of carnitine and carnitine esters. In the second group of infants, after administration of 500 μmol dTML the plasma-free carnitine concentration increased (from 9.95 ± 0.63 to 12.9 ± 0.87 nmol/ml, p > 0.05) with a significant increase in the urinary excretion of free carnitine on the day of dTML administration and on the posttreatment day (from 4.79 ± 1.36 to 9.85 ± 1.18 and to 17.5 ± 2.31 μmol/day, respectively). Analysis of urine using fast atom bombardment mass spectrometry (FAB-MS) revealed only the presence of the dTML in the urine of the newborns; no change was detected in the relative abundance of any other carnitine precursor. Surprisingly, in the second group, which received the higher dose of dTML supplement, only the signal intensity of the unlabeled carnitine increased after dTML administration; no new peak appeared in the urine that would correspond to the de novo synthesized carnitine containing the stable isotope-labeled trimethyl group of dTML. Thus, the FAB-MS analysis clearly demonstrated that contrary to the likely prediction, the 270% extra free carnitine output was a consequence of a dose-dependent dTML-induced depletion of the free carnitine reserves from the newborns. The absence of the incorporation of the label from dTML into carnitine strongly suggests that circulating TML is not the precursor of carnitine in premature infants.
Plasma Homocysteine Concentrations of Preterm Infants
Authors: Hongsprabhas Pranithi , Saboohi Farhad , Aranda Jak V. , Bardin Claudette L. , Kovacs Lajos B. , Papageorgiou Apostolos N. , Hoffer L. John 
Published: April 2003

Mild hyperhomocysteinemia in adults is associated with an increased risk of vascular disease. Although information is available about plasma homocysteine concentrations in childhood, data are entirely lacking for preterm infants despite their known abnormalities of sulfur amino acid metabolism. We measured plasma total homocysteine concentrations of 9 preterm infants (gestational age 23–31 weeks) within 48 h of birth and over the subsequent 14 days of life, and 4 term infants (gestational age 36–39 weeks) on a single occasion within 72 h of birth. As measured within 48 h of birth, average plasma homocysteine and cysteine concentrations of the preterm infants were 3.8 ± 0.3 and 122 ± 8 μ<i>M</i>, both significantly less than those of the term infants (6.1 ± 1.3 and 187 ± 39) and of normal adults (8.2 ± 0.5 and 232 ± 6). Plasma homocysteine (but not cysteine) appeared to gradually increase during the first 2 weeks of life (p = 0.053). Our results indicate that hyperhomocysteinemia does not normally occur in preterm infants.
Failure of Gamma-Interferon to Decrease Mortality from Group B Streptococcal Sepsis in Neonatal Rats
Authors: Wittler Robert R. , Harris Richard W. , Paine Donald D. 
Published: April 2003

Newborns possess an altered immune response to infection with impaired leukocyte chemotaxis and deficient production of gamma-interferon (IFN-γ). IFN-γ enhances neonatal leukocyte activation and movement. We proposed that IFN-γ in conjunction with penicillin compared to penicillin therapy without IFN-γ would increase survival from group B streptococcal sepsis in a neonatal rat model. Newborn rats were infected with 10<sup>5</sup> cfu of group B streptococci at 48–72 h of age and randomized to receive either serum albumin (controls), rat recombinant IFN-γ, albumin and penicillin, or IFN-γ and penicillin. Survival 120 h postinfection revealed: controls 5% (1/21); IFN-γ 4% (1/24); penicillin 23% (5/22); and IFN-γ plus penicillin 10% (2/21). Survival analysis with a lognormal parametric regression model revealed only the penicillin group to have improved survival compared to controls. Contrasting the penicillin group with the IFN-γ plus penicillin group did not reveal a statistically significant difference by the Wald χ<sup>2</sup> statistic (p = 0.25).
Influence of Nasopharyngeal CPAP on Breathing Pattern and Incidence of Apnoeas in Preterm Infants
Authors: Kurz Herbert 
Published: April 2003

Continuous positive airway pressure (CPAP) applied by endotracheal (ET) tube in the pharynx (nasopharyngeal CPAP, n-CPAP) is widely used for the treatment of mild respiratory distress syndrome and of apnoeas of prematurity. Effects on breathing pattern and on different types of apnoeas are not fully understood. We wanted to know the effect of discontinuing n-CPAP on the respiratory rate, apnoeas and bradycardia/desaturation events. Thirteen prematurely born infants with bradycardia and/or desaturation events were studied when weaning from n-CPAP was clinically considered. Polygraphic studies were performed for 2 h during n-CPAP therapy and for 2 h without CPAP. Nasal flow was measured by registering expiratory pCO<sub>2</sub> at the free nostril opening. During n-CPAP, the respiratory rate was significantly lower, there were fewer obstructive apnoeas, more short central apnoeas (6–9 s) and less severe apnoea-associated desaturations. During n-CPAP, the infants spent significantly more time in a state of quiet breathing.
Early (4–7 Days of Age) Dexamethasone Therapy for Prevention of Chronic Lung Disease in Preterm Infants
Authors: Tsukahara Hirokazu , Watanabe Yasuhiro , Yasutomi Motoko , Kobata Ritsuyo , Tamura Satoshi , Kimura Kouki , Hiraoka Masahiro , Mayumi Mitsufumi 
Published: April 2003

We conducted a comparative study to evaluate whether early (4–7 days of age) low-dose dexamethasone (DEX) therapy in preterm infants with surfactant-pretreated respiratory distress syndrome (RDS) would facilitate extubation and improve the clinical outcome. Twenty-six preterm infants with surfactant-pretreated RDS who were oxygen- and ventilator-dependent at 4 days of postnatal age were enrolled. Twelve infants were in the historical comparison group, and 14 infants were assigned to receive DEX 0.125 mg/kg i.v., every 12 h, for a total of 6 doses. At study entry, the two groups had a comparable clinical status. DEX therapy significantly facilitated weaning from mechanical ventilation (median interval, 6 vs. 24 days, p < 0.005) and shortened duration of oxygen supplementation (9 vs. 28 days, p < 0.05) as compared with the historical comparison group. At 28 days of age, the occurrence of chronic lung disease (CLD) was significantly lower (1/14 vs. 6/12, p < 0.05) and there was a significant decrease in the incidence of ventilator dependence (0/14 vs. 5/12, p < 0.05) in the DEX group. DEX therapy did not influence the incidence of significant complications such as infection, periventricular leukomalacia or retinopathy of prematurity. We conclude that in a selected high-risk group of preterm infants, early low-dose DEX treatment results in improvement in pulmonary outcome without significant side effects.
Changes in Body Composition during the Initial Hours of Life in Breast-Fed Healthy Term Newborns
Authors: Rodríguez Gerardo , Ventura Purificación , Samper Maria Pilar , Moreno Luis , Sarría Antonio , Pérez-González José M. 
Published: April 2003

Newborns usually lose 5–10% of their initial weight during the first 4 days of life. Our aim, using bioelectrical impedance (BI), was to study the body composition of healthy term newborns and the nature of the changes which accompany this physiological weight loss. Forty-three healthy term newborns, all with adequate weight for their gestational age, were studied during the first 3 days of life. Weight and BI were taken on the 1st, 2nd, and 3rd days of life, always at the same time of the day. Total body water (TBW), percentage of total body mass hydration (%TBW), and amount of body solids were calculated. Average weight at birth was 3,297 ± 381 g, length 50.04 ± 1.75 cm, and gestational age 39.9 ± 0.84 weeks. Weight, TBW, and body solids decreased progressively during the first 3 days of life (p < 0.000). By day 3, weight loss represented 5.67 ± 1.98% of birth weight, but %TBW increased slightly (1.72%; p < 0.000). These results suggest that, during physiological weight loss, body composition modifications are produced in the term newborn by a decrease in TBW and loss of body solids. The level of body hydration increases slightly, since the loss of body solids is greater than the loss of TBW. The use of BI can help us in the study of body composition and the short- and/or long-term changes produced therein, in the newborn.
Influence of Mild Hypothermia after Hypoxia-Ischemia on the Pharmacokinetics of Gentamicin in Newborn Pigs
Authors: Šatas Saulius , Hoem Nils Ove , Melby Kjetil , Porter Helen , Lindgren Carl G. , Whitelaw Andrew , Thoresen Marianne 
Published: April 2003

The renal function is often affected in asphyxiated newborn infants. The pharmacokinetics of drugs like aminoglycosides eliminated through the kidneys may be impaired and require a different than usual dosage regimen. A decrease in body temperature is associated with a decrease in glomerular filtration rate and may, therefore, impair the elimination of aminoglycosides. When hypothermia is applied as neuronal rescue therapy after birth asphyxia, the pharmacokinetics of kidney-eliminated drugs may be impaired even more. We used our well-established global hypoxia-asphyxia newborn pig model to evaluate the effect of mild hypothermia after hypoxia-ischemia on gentamicin pharmacokinetics. Newborn pigs underwent global hypoxia-ischemia followed by normothermia (39°C) for 72 h (n = 8) or mild hypothermia (35°C) for 24 h followed by normothermia (39°C) for 48 h (n = 8). Gentamicin pharmacokinetics was studied after three gentamicin doses: before hypoxia-ischemia, after hypoxia-ischemia during mild hypothermia or normothermia, and during normothermia 48 h after the first dose. The gentamicin pharmacokinetics variables were calculated using a SAAM II program. Hypoxia-ischemia altered renal function and gentamicin pharmacokinetics. The gentamicin clearance correlated with the creatinine plasma concentration (r = 0.89) and with the kidney pathology score (r = 0.55). There was no significant difference in gentamicin pharmacokinetics at 35 and 39°C in newborn pigs after hypoxia-ischemia. The gentamicin pharmacokinetics variables were not different in the hypothermic or normothermic pigs after all three studied doses. Mild hypothermia for 24 h after hypoxia-ischemia does not affect gentamicin pharmacokinetics.
Effect of Cisapride on Acid Gastro-Oesophageal Reflux during Treatment with Caffeine
Authors: Kentrup H. , Baisch H.-J. , Kusenbach G. , Heimann G. , Skopnik H. 
Published: April 2003

About 50% of preterm infants and neonates receiving methylxanthines for respiratory stimulation will develop a pathological gastro-oesophageal reflux (GOR) pattern. In the face of potential GOR-related complications the effect of a concomitant treatment with a prokinetic agent, such as cisapride, should be evaluated. In this study 32 formerly preterm infants were studied simultaneously by 24-hour oesophageal pH monitoring and cardio-respirogram before the presumed end of caffeine treatment. In 14 of these infants a reflux index (RI; percentage of recording time) of more than 4% could be detected (pH <4). Ten of them were treated orally with cisapride (0.2 mg/kg t.i.d.). Data of pH monitoring, cardio-respirogram and caffeine serum concentrations were obtained before and 5 days after introducing cisapride. The RI and the frequency of GOR decreased significantly with cisapride. The steady-state serum concentrations of caffeine were not influenced by cisapride and the extent of periodic breathing remained unchanged. In conclusion, cisapride has a positive influence on GOR parameters during caffeine treatment without impairing the oral bioavailability or therapeutic effect of caffeine.