bluuebunny/crossref_metadata_2025 huggingface dataset:
Frequency-Specific Threshold Determination with the CERAgram Method: Basic Principle and Retrospective Evaluation of Data
Authors: Ross Bernhard , Lütkenhöner Bernd , Pantev Christo , Hoke Manfried
Published: April 2003

A method for the objective evaluation of the hearing threshold using cortical evoked response audiometry was developed. The method results in a kind of objective audiogram, visualizing the significance of an auditory evoked potential (AEP) in a scheme similar to a conventional audiogram. In the present implementation of the method, four frequencies are tested quasi-simultaneously (500, 1000, 2000 and 3000 Hz; intensity steps of 5 dB). The significance of an evoked potential is assessed by means of the Rayleigh test, which is applied to the phase values derived from certain time windows of the single-trial epochs. A retrospective analysis of 1,920 threshold estimations in 240 subjects suggested that the detection threshold (lowest stimulus intensity yielding a significant response) was, on the average, 7.5 dB above the electrophysiological threshold (intensity where the AEP amplitude vanishes). The grand-average amplitude-intensity characteristic was approximated by the function a(1 – exp(–I/b)), with a = 6.25 μV, b = 22.3 dB and I representing the intensity (in decibels) relative to the electrophysiological threshold.
Vibro-Acoustic Modelling of the Outer and Middle Ear Using the Finite-Element Method
Authors: Prendergast Patrick J. , Ferris Peter , Rice Henry J. , Blayney Alexander W.
Published: April 2003

In this study, a computer-based method called finite-element analysis is used to predict the forced-frequency response of the ear, with and without an ossicular replacement prosthesis (PORP 0362, Xomed Surgical Products). The method allows visualisation of the dynamical behaviour of the tympanic membrane (TM) and of the ossicles. The finite-element model is fully three-dimensional and includes both ligaments and muscles, and accounts for damping caused by the TM, ligaments, incudostapedial joint and the fluids of the inner ear. For validation, comparison is made with experimental measurements of umbo displacement taken from the literature. The translation and rotation (both anterior-posterior and inferior-superior) of the stapedial footplate are investigated. It is predicted that the translatory motion of the footplate decreases with increasing frequency, except when the frequency of the acoustic signal matches the natural frequencies of the ossicular chain or outer ear canal. The tilting motion of the stapedial footplate is also predicted to depend on frequency of excitation. The presence of a prosthesis changes the dynamical response considerably by shifting the natural frequencies of the ossicular chain. Ratios of stapes motion with and without the prostheses are plotted as a function of frequency allowing this effect to be clearly observed.
Determination of the Shape and Inertia Properties of the Human Auditory Ossicles
Authors: Weistenhöfer Christian , Hudde Herbert
Published: April 2003

This paper describes a method to accurately determine the shape of the human middle ear ossicles. If the density and the shape of a body are known, the inertia properties can be calculated using commercially available software. The inertia properties have been calculated for the stapes and for the incudomalleal unit. Different rectangular views of the stapes and the incudomalleal unit are shown to depict the position of the center of gravity and the position of the principal axes of inertia.
Mismatch Negativity: Clinical and Other Applications
Authors: Näätänen Risto , Escera Carles
Published: April 2003

The perspectives of application of the mismatch negativity (MMN), generated by the brain’s automatic response to change in auditory stimulation, are discussed. In light of the fact that the MMN (and its magnetic equivalent MMNm) currently provides the only objective measure of the accuracy of the central auditory function, these perspectives appear very promising. The MMN can be measured in the absence of attention and task requirements, which makes it particularly suitable for testing different clinical populations and infants. Furthermore, the MMN enables one to evaluate the accuracy of auditory discrimination separately for any acoustic feature, such as frequency, intensity and duration, and for learned categories, such as the phonemes of a particular language. In addition, by measuring the decay of the MMN amplitude as a function of the interstimulus interval, it is possible to estimate the duration of sensory (echoic) memory.
Acute and Chronic Effects of Alcohol on Preattentive Auditory Processing as Reflected by Mismatch Negativity
Authors: Ahveninen Jyrki , Escera Carles , Polo M. Dolores , Grau Carles , Jääskeläinen Iiro P.
Published: April 2003

Chronic alcoholism, a major worldwide health problem, is associated with a variety of neurocognitive changes in the afflicted individuals. The precise neurophysiological basis of these changes is not yet understood. Mismatch negativity (MMN) is a preattentive event-related potential component indexing cortical auditory memory traces and automatic change detection in the brain that can be used to study the neural basis of cognitive impairments in various neurodegenerative diseases. MMN studies have revealed that even a low dose of acute alcohol significantly impairs automatic change detection and involuntary attention shifting. Recent MMN results on chronic alcoholism in turn suggest that auditory sensory traces decay slightly faster and are substantially more vulnerable to the distracting effect of backward masking in alcoholics than in healthy subjects. Furthermore, chronic alcohol abuse might accelerate the age-related impairment of automatic change detection. There is also evidence that the MMN changes might predict impaired performance in behavioral memory and attention tasks in alcoholics. In MMN studies of detoxified alcoholics, however, many confounding factors have to be taken into account. For instance, postwithdrawal brain hyperexcitability might be associated with a slightly enhanced or accelerated MMN/MMNm (the magnetic equivalent of MMN). In sum, MMN and MMNm provide an objective noninvasive tool for exploring the neurophysiological functional deficits related to both acute alcohol intoxication and chronic alcoholism.
The Stable Microbubble Test on Tracheal Aspirate Samples from Newborn Babies for Diagnosis of Surfactant Deficiency and/or Surfactant Malfunction
Authors: Friedrich W. , Haufe M. , Schmalisch G. , Wauer R.R.
Published: April 2003

For predicting the risk of respiratory distress syndrome (RDS), lung surfactant in amniotic fluid can be assessed by observation of stable microbubbles (<15 µm diameter). It was investigated if the stable microbubble test (MT) developed on amniotic fluid could be applied on tracheal aspirate samples (TA) obtained from newborn infants. Forty-four TA from 29 newborn infants without pulmonary diseases (group 1) and 65 TA from 21 newborn infants with respiratory insufficiency (group 2) were analyzed by the MT for predicting surfactant deficiency and/or surfactant malfunction. Ten microbubbles/mm2 was defined as cutoff value of the MT. A specificity of 90% and a sensitivity of 52% was obtained with this cutoff value. A much lower rate of false negative results (sensitivity 91%) was noted after surface tension measurement of TA. The sensitivity of the MT (52%) does not encourage the use of the MT on TA.
Organ Pathology following Mild Hypothermia Used as Neural Rescue Therapy in Newborn Piglets
Authors: Amess P.N. , Penrice J. , Howard S. , Thoresen M. , Edwards A.D. , Cady E.B. , Wyatt J.S. , Sams V.
Published: April 2003

The aim of this study was to assess the possible adverse effects of hypothermia, used as neural rescue therapy in a newborn piglet model. Sixteen newborn piglets were subjected to transient cerebral hypoxia-ischaemia by temporary occlusion of the carotid arteries and reduction of the fractional inspired oxygen to 0.12. On resuscitation 11 piglets were maintained normothermic (38.5–39.0°C) and, in order to assess the cerebroprotective effect of hypothermia, 5 piglets were cooled to 35°C for 12 h before normothermia was resumed. At 48 or 64 h following resuscitation the animals were sacrificed and the heart, left kidney, specimens of distal small bowel, lung and liver were removed and histologically sectioned. No microscopic abnormalities of the heart, bowel or lung were observed in hypothermic or normothermic animals. All kidney specimens were normal except one from the normothermic group. Abnormal liver pathology suggestive of hypoperfusion injury was found in 5 normothermic and 3 hypothermic piglets. There was no significant difference in the proportion of piglets with liver abnormality between the two groups. Mild hypothermia following cerebral hypoxia-ischaemia in the newborn piglet was not associated with an increased incidence of non-cerebral organ damage. The hepatic injury observed may be related to umbilical venous catheterisation and has potential relevance to neonatal intensive care.
Inhaled Nitric Oxide neither Alters Oxidative Stress Parameters nor Induces Lung Inflammation in Premature Lambs with Moderate Hyaline Membrane Disease
Authors: Storme L. , Zerimech F. , Riou Y. , Martin-Ponthieu A. , Devisme L. , Slomianny C. , Klosowski S. , Dewailly E. , Cneude F. , Zandecki M. , Dupuis B. , Lequien P.
Published: April 2003

The purpose of this investigation was to examine whether inhaled nitric oxide (NO) may alter oxidative stress parameters and induce lung inflammation in moderate hyaline membrane disease (HMD). Eighteen moderately premature lambs (130 days gestation, term = 147 days) were randomly assigned to treatment with 20 ppm inhaled NO (n = 8) from the onset of ventilation or used as control (n = 10). Except inhaled NO, treatments were intentionally similar to those applied in clinical situations. The main studied parameters were oxidative stress index measurements on lung parenchyma and in circulating blood, lung parenchyma microscopic examination and bronchoalveolar lavage cell count. We found that 20 ppm of inhaled NO for 5 h did not change significantly either malondialdehyde and total antioxidant status levels in circulating blood, or malondialdehyde, reduced glutathione, glutathione peroxidase and glutathione reductase in lung parenchyma. Amino-imino-propene bond generation, which are lipoperoxidation markers, was similar in both groups. Furthermore, no significant changes in the number of inflammatory cells in lung lavage products and in lung parenchyma microscopic examination could be found. Therefore, these data do not support the hypothesis that short-term NO inhalation increases oxidative stress and lung inflammation in an experimental model of moderate HMD.
The Effect of Phototherapy on Renal Blood Flow Velocity in Preterm Infants
Authors: Benders Manon J.N.L. , van Bel Frank , van de Bor Margot
Published: April 2003

Mean renal blood flow velocity (RBFV) was studied with two-dimensional/pulsed Doppler ultrasound and relative renal vascular resistance (RVR) was calculated before, during, and after phototherapy treatment in 30 preterm infants (gestational age ≤32 weeks) who were treated for a minimum of 12 h with phototherapy for nonhemolytic hyperbilirubinemia. RBFV decreased, whereas RVR increased significantly after the initiation of phototherapy. In ‘healthy’ (nonventilated) infants RBFV and RVR returned to baseline values after discontinuation of phototherapy. Whereas in ‘unhealthy’ (ventilated) infants, RBFV and RVR did not return to baseline values after discontinuation of phototherapy. In 16 infants (>50% of the cases) the ductus arteriosus reopened during phototherapy.
Effects of Intravenous Infusions of Noradrenaline on Renal Function in Chronically Catheterised Fetal Sheep
Authors: McMullen Julie R. , Gibson Karen J. , Lumbers Eugenie R.
Published: April 2003

To determine the effects of circulating noradrenaline on fetal renal function noradrenaline was infused intravenously into 7 chronically catheterised fetal sheep (127–138 days) at a dose (1 µg/kg/min) which resulted in plasma levels similar to those which occur during hypoxia. Fetal mean arterial pressure increased by approximately 14 mm Hg (p < 0.001) and haematocrit rose (p < 0.005). Glomerular filtration rate rose from 3.85 ± 0.47 (SEM) to 4.70 ± 0.50 ml/min (p < 0.05) during the first hour and fractional reabsorption of sodium by the proximal tubule fell (p < 0.05) during the second hour. Urine flow rate increased from 0.61 ± 0.13 to 1.18 ± 0.24 ml/min (p < 0.001) and osmolar excretion increased from 78 ± 15 to 153 ± 36 µosm/min (p < 0.005). By contrast lung liquid flow fell (p < 0.05), but the increase in urine flow was much greater than the decline in lung liquid. These findings suggest that during hypoxia, noradrenaline may play an important role in the maintenance of urine flow and consequently amniotic fluid volume and, as suggested by others, in the distribution of fluid between the vascular and interstitial compartments.
Brief, Intermittent Hypoxia Restricts Fetal Growth in Sprague-Dawley Rats
Authors: Schwartz Jonathan E. , Kovach Andras , Meyer Joseph , McConnell Carol , Iwamoto Harriet S.
Published: April 2003

This study was conducted to determine whether brief, intermittent exposure to hypoxia with little change in nutrient intake would affect fetal growth. Pregnant rats were exposed to 1 or 2 h of hypoxia (FiO2 = 0.09–0.095) from days 15 to 19 of gestation. Exposure to 1 h of hypoxia decreased fetal body weight and length, liver weight and increased the brain/liver weight ratio (p < 0.05) as compared to controls. Two hours of hypoxia decreased fetal body weight and length, and heart, lung, kidney, gut, brain and liver weights (p < 0.01), but did not affect the brain/liver weight ratio. Two hours of hypoxia decreased maternal food intake and weight gain (p < 0.05), but fetal growth was not significantly altered in pair-fed controls. These data demonstrate that brief, intermittent periods of intrauterine hypoxia have significant effects on fetal growth.
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 H2O until both the a/A ratio was <0.12 and a peak inspiratory pressure (PIP) >20 mbar was needed to keep the tidal volume (VT) at 10 ml/kg. Surfactant (Survanta®) 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 PaCO2), four indices of lung function (functional residual capacity, FRC, dynamic lung compliance, Crs, VT and the alveolar portion of VT) 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 Crs by +22% whereas VT 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 H2O [Krause et al., Am J Respir Crit Care Med 1997;156:862–866], significant differences have been disclosed for Crs, VT and FRC. In conclusion, the enhancement of surfactant effect by VRM largely depends on the preexisting distension of the lungs.
Human Milk: Nutritional Aspects of a Dynamic Food
Authors: Picciano Mary Frances
Published: April 2003

The composition and volume of human milk progressively changes with the onset and duration of lactation and can be influenced by maternal nutritional factors. Current evidence indicates that infant demand is the major determinant of the quantity of milk transferred to the nursing infant. Human milk is remarkable for its variability, and ranges of intakes of milk constituents are comparable with normal patterns of infant growth and development. Lipids are by far the most variable constituents in human milk with both long-term maternal nutrition states and daily intake capable of exerting an influence. Maternal vitamin intake bears a strong relationship to milk content, and appropriate intakes of vitamins D and K may not always be furnished to nursing infants. Major and trace minerals in human milk are not greatly affected by maternal diet, with selenium and iodine being notable exceptions. Compartmentalization and molecular forms of the trace elements in human milk are associated with high infant bioavailability. The success of lactation should be measured using maternal and infant indices of nutritional adequacy.
Cytokines, Chemokines, and Colony-Stimulating Factors in Human Milk: The 1997 Update
Authors: Garofalo Roberto P. , Goldman Armond S.
Published: April 2003

Epidemiologic studies conducted over the past 30 years to investigate the protective functions of human milk strongly support the notion that breast-feeding prevents infantile infections, particularly those affecting the gastrointestinal and respiratory tracts. However, more recent clinical and experimental observations also suggest that human milk not only provides passive protection, but also can directly modulate the immunological development of the recipient infant. The study of this remarkable defense system in human milk has been difficult due to its biochemical complexity, the small concentration of certain bioactive components, the compartmentalization of some of these agents, the dynamic quantitative and qualitative changes of milk during lactation, and the lack of specific reagents to quantify these agents. Nevertheless, a host of bioactive substances including hormones, growth factors, and immunological factors such as cytokines have been identified in human milk. Cytokines are pluripotent polypeptides that act in autocrine/paracrine fashions by binding to specific cellular receptors. They operate in networks and orchestrate the development and functions of the immune system. Several different cytokines and chemokines have been discovered in human milk over the past years, and the list is growing very rapidly. This article will review the current knowledge about the increasingly complex network of chemoattractants, activators, and anti-inflammatory cytokines present in human milk and their potential role in compensating for the developmental delay of the neonate immune system.
Early and Late Effects of Breast-Feeding: Does Breast-Feeding Really Matter?
Authors: Villalpando Salvador , Hamosh Margit
Published: April 2003

Breast-feeding protects the newborn against infectious diseases in developing as well as in industrialized countries. Protection is conferred against gastrointestinal and respiratory tract diseases as well as against otitis media. This protection provided by specific (antibody dependent) and broad, nonspecific protective factors in human milk (proteins, glycoproteins, and lipids) is associated with lower global morbidity and mortality of breast-fed infants as compared with formula-fed infants. While protection against diseases that develop later in life, such as insulin-dependent diabetes mellitus, inflammatory bowel disease, and childhood cancer, has been reported, well-planned prospective studies are essential in order to confirm these observations. Similar studies are essential in order to ascertain the small but consistently reported higher cognitive ability of breast-fed infants.
Developmental Changes in Apolipoprotein B Gene Expression in the Liver of Fetal Calves
Authors: Gruffat Dominique , Piot Cécile , Durand Denys , Bauchart Dominique
Published: April 2003

Changes in apolipoprotein (apo B) gene expression in the liver were determined in fetal calves from 90 to 260 days of intrauterine life. Results were compared with those obtained from the livers of 1-month-old calves and adult cows. By Western blot analysis using a rabbit antiserum to bovine apo B, apo B100 was detected from 90 days of intrauterine life. Apo B100 was shown to be the only form of apo B detected in the liver of fetal calves whatever the gestational age indicating the lack of editing process during the prenatal period. Hepatic apo B contents were stable during intrauterine life and comparable to those of calves and lower than those of cows. Hepatic contents of apo B mRNA increased with the gestational age similarly to total RNA. Values of apo B mRNA at 260 days of intrauterine life were comparable to those in the liver of 1-month-old calves and adult cows. These results suggested that hepatic synthesis of calf apo B during fetal development is specifically regulated at a posttranscriptional level, either by a decrease in the rate of translation and/or by an increase in the rate of intracellular apo B degradation.
Surface Tension, Glutathione Content and Redox Ratio of the Tracheal Aspirate Fluid of Premature Infants with IRDS
Authors: Boda Domokos , Németh Ilona , Pintér Sándor
Published: April 2003

Objective: Determination of the surface tension (ST), the total glutathione (GL) content and the ratio of oxidized glutathione (GSSG) to reduced glutathione (GSH) in the tracheal aspirate (TA) of newborn infants with IRDS. Methods: The ST of the TA was determined by monitoring the fluid level pulsated in a capillary glass tube by means of a digitalized videocomputerized picture analysis program, a technique developed in our laboratory. The concentrations of GSSG and total GL in the TA were determined enzymatically with glutathione reductase. All results of laboratory tests were referred to the total phospholipid (PL) concentration. Patients, Experimental Material: TA samples were collected from 32 intubated premature and newborn infants admitted to the NICU with IRDS during the first 2 weeks of their lives. Control samples were obtained from 11 children prior to elective surgery. Results: The ST relative to the PL content (surface tension index, STI) was significantly lower in the newborns with IRDS than in the control group, and the concentration of GSH in the TA was also markedly decreased in all IRDS infants studied. The concentration of GSSG and the ratio of GSSG to GSH were significantly higher in the severe cases and in those with an unfavourable prognosis. Surfactant treatment had a protective effect against oxidative stress, it induced a decrease in both the GSSG concentration and in the GL redox ratio (GSSG/GSH) in the TA. There was a close correlation between the GSH content and the STI value of the samples studied. Conclusion: Oxidation and consequent depletion of GSH in the TA may be an aggravating factor in the development of the insufficient surface activity in intubated newborns with IRDS.
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. Conclusion: 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.
Severe Pulmonary Hemorrhage in the Premature Newborn Infant: Analysis of Presurfactant and Surfactant Eras
Authors: Braun Krista R. , Davidson Karen M. , Henry Margaret , Nielsen HeberC.
Published: April 2003

We undertook a case-control study of premature infants who developed clinically significant, severe pulmonary hemorrhage (PH) in the presurfactant and surfactant eras to learn more about the cause of severe PH and whether the pathogenesis of severe PH has changed with the advent of surfactant therapy. Severe PH was defined as an acute onset of severe endotracheal bleeding with an acute drop in hematocrit and the development of multilobar infiltrates on chest radiograph. Eleven premature infants from the presurfactant era population and 17 premature infants from the surfactant era population met the criteria for severe PH, all with gestational ages <32 weeks and birth weights <1,500 g (very low birth weight infants). These were each matched by gestational age, date of birth, birth order (for twins), and birth weight to 2 controls. The
incidence of severe PH in infants of gestational age <32 weeks was similar in the two eras (1.8% in the presurfactant era and 3.0% in the surfactant era). Severe PH was not associated with maternal characteristics such as drug use or prenatal care, pregnancy
complications, evidence of intrauterine anoxia, hyaline membrane disease, frequency of
endotracheal suctioning, or patent ductus arteriosus. Premature infants suffering from
severe PH in the presurfactant era required more delivery room resuscitation and had
more severe early respiratory disease during the first 12 h of life as compared with their
controls. However, these differences were not present in the group from the surfactant
era. Infants with severe PH were more likely to have birth weights below the third percentile for gestation (severe intrauterine growth restriction). The proportion of infants receiving surfactant, and the number of surfactant doses used, did not differ between severe-PH
infants and their controls in the surfactant era group. We conclude that severe intrauterine
growth restriction represents a risk factor for severe PH in very low birth weight infants.
The introduction of surfactant therapy has not altered the incidence of severe PH, even
though it has apparently helped remove the severity of early lung disease as a risk factor.
The physiological basis of severe PH requires further investigation.
Smooth Muscle Expresses Bone Morphogenetic Protein (Vgr-1/BMP-6) in Human Fetal Intestine
Authors: Perr Hilary A. , Ye Jian-Qin , Gitelman Stephen E.
Published: April 2003

During human fetal development, autocrine TGF-β1 regulates the synthesis of specific collagen types by intestinal smooth muscle cells in an age-dependent manner. Vgr-1/BMP6, a member of the TGF-β superfamily, modulates epithelial, endochondral and neural tissue development in mice: a related peptide is essential to gut morphogenesis in Drosophila. This is the first study to detect vgr-1/BMP-6 during human intestinal organogenesis. Polyclonal antibodies to the precursor and mature fragments of vgr-1 were used in immunohistochemical studies of human intestine at 15, 19 and 24 weeks’ gestation. Immunoreactivity was detected with the antibody directed against the precursor portion of vgr-1. Only smooth muscle structures stained for vgr-1 including muscularis propria, muscularis mucosa and vasculature. BMP-6 mRNA was detected by RNase protection assay in cultured muscle cells from 11, 17 and 22 weeks’ gestation. This study demonstrates vgr-1/BMP 6 expression in the developing human fetal intestine, exclusively in muscle.
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 10–8 and 10–5 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.
Pain-Relieving Effect of Sucrose in Newborns during Heel Prick
Authors: Overgaard Charlotte , Knudsen Aage
Published: April 2003

We assessed the effect of sucrose as a pain reliever in a population of newborns when cuddled and comforted during heel prick for diagnosis of phenylketonuria. In addition, the influences of gender, gestational age, postnatal age, ponderal index and behavioural state of the infant before the heel prick were studied, as judged by the neonatal infant pain scale (NIPS) score, on crying time (CT) and subsequent NIPS score. 100 healthy full-term infants were enrolled in this double-blind, randomized controlled trial. Before the heel prick, the newborns, when cuddled by the parent(s), were either given 2 ml 50% sucrose solution or 2 ml sterile water. The sessions were videotaped and analyzed for determination of CT and NIPS scores. The frequency distribution of CT showed a bimodal pattern in both the sucrose and the placebo groups. Sucrose significantly reduced CT and NIPS scores after the heel prick. No influence of gender, gestational age, postnatal age or ponderal index on CT was found. NIPS scores before the heel prick correlated significantly and positively with CT and subsequent NIPS scores in both the sucrose and the placebo groups. Intra-orally administered sucrose given before heel prick can be recommended as a useful pain reliever. Furthermore, the findings indicate that factors calming the newborn and creating low NIPS scores before the procedure can reduce the pain reaction equivalently and additively to sucrose administration.
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.
Effect of Maternal Polyunsaturated Fatty Acid Concentration on Transport by the Human Placenta
Authors: Haggarty P. , Ashton J. , Joynson M. , Abramovich D.R. , Page K.
Published: April 2003

The role of the placenta in controlling the supply of fatty acids to the fetus was investigated in term placentas (n = 5) from normal pregnancies. The maternal side was perfused ex vivo for 90 min with a modified Krebs Ringer solution containing a physiological mixture of fatty acids – designed to mimic the composition of non-esterified fatty acids (NEFA) measured in the last trimester of pregnancy (n = 10) – and ratio of fatty acid to human albumin. The selectivity for α-linolenic acid (αLN) transfer to the fetal circulation was not significantly different from that observed when using the triglyceride (TG) composition (1.21 ± 0.04), but significantly different for AA (1.43 ± 0.12; p < 0.001) and docosahexaenoic acid (DHA; 2.02 ± 0.09; p = 0.048). The absolute rate of transfer (nmol · ml–1) compared to that using the TG maternal perfusate composition was significantly different for LA (0.562 ± 0.038; p = 0.50), αLN (0.130 ± 0.009; p < 0.001), arachidonic acid (AA; 0.218 ± 0.022; p = 0.001) and DHA (0.383 ± 0.04; p < 0.001). Thus, placental selectivity for αLN and DHA appears to be relatively unresponsive to changes in the mixture of fatty acids in the maternal circulation but the selectivity for AA increased with the increase in the maternal AA concentration. For an 8-fold increase in the concentration of DHA in the maternal circulation there was a 13-fold increase in the transfer of DHA to the fetal circulation. For a 2-fold increase in the concentration of AA, transfer was increased 8-fold. For a 1.3-fold increase in the concentration of αLN, transfer was increased 2.1-fold. These results suggest that the maternal concentration of individual fatty acids, and hence the composition of the maternal diet, can have large effects on polyunsaturated/long-chain polyunsaturated fatty acids delivery to the fetus.
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-[d9]-L-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.
Adrenocortical Imprint in the Fetus of a Diabetic Gestation
Authors: Malee Maureen P. , Wu Ke-Ying
Published: April 2003

Offspring of diabetics are at increased risk for diabetes as adults. As corticosteroids are intimately involved in glucose homeostasis, we investigated aspects of corticosteroid activity in the late gestation fetuses of control, moderately diabetic and insulin-controlled streptozotocin-induced diabetic rats. We found that moderate maternal diabetes had no effect upon litter size or fetal body weight. Uncontrolled maternal diabetes was accompanied by fetal hyperglycemia, hyperinsulinemia and elevated aldosterone. Maternal insulin treatment normalized fetal glucose and aldosterone; fetal insulin and corticosterone levels increased. Maternal diabetes had no effect upon fetal adrenal expression of P450scc mRNA; the abundance of P450c11β mRNA increased, and returned to that of the control gestation upon insulin treatment. P450c11AS mRNA was barely detectable, and decreased in the fetuses of insulin-treated diabetics. P450c11B3 mRNA was undetectable in all fetal groups. Our results implicate aspects of maternal diabetes in the expression of a fetal adrenocortical imprint, manifested as a greater abundance of P450c11β mRNA. Although not accompanied by elevated corticosterone in the fetus, this imprint could ultimately allow for greater potential corticosterone production in response to typical stimuli, and thus contribute to the tendency towards glucose dysregulation in these offspring of diabetic gestations.
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 μM, 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.
Expression of Intestinal Trefoil Factor in Developing Rat Intestine
Authors: Lin Jing , Holzman Ian R. , Jiang Ping , Babyatsky Mark W.
Published: April 2003

Intestinal trefoil factor (ITF or TFF3), a small peptide secreted at the mucosal surface by goblet cells throughout the mature intestine, appears to play important roles in the maintenance and repair of the intestinal mucosal barrier. To study the expression of TFF3 during development, intestinal tissues were collected from rats at different development stages and examined by Northern blot analysis, Western blot analysis and immunohistochemical staining for TFF3 mRNA and protein expression. The results demonstrate that rat TFF3 mRNA is not detected until the 17th gestational day (term = 22 days), the expression is greater on gestational day 20 and increased further postnatally. TFF3 protein is first detected by Western blotting and immunohistochemical staining on gestational day 20. Further increases in TFF3 protein expression are demonstrated at around the weaning period. In conclusion, significant expression of rat TFF3 commences late in gestation and its expression is relatively deficient in immature rats. Expression of TFF3 may be deficient in premature infants and, therefore, may have a role in the development of necrotizing enterocolitis.
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 105 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 χ2 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 pCO2 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.