bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma Arginine Levels and the Response to Inhaled Nitric Oxide in Neonates
Authors: Kavvadia Vasiliki , Greenough Anne , Lilley Julia , Laubscher Bernard , Dimitriou Gabriel , Boa Frances , Poyser Karen
Published: April 2003

Inhaled nitric oxide (iNO) can be an effective vasodilator in pulmonary hypertension of the newborn (PHN). The aim of this study was to determine whether differences in arginine levels, from which endogenous NO is produced, explain the variability in response to NO and whether the arginine levels were lower in term and preterm infants with PHN than in infants without PHN (controls). We prospectively studied 30 infants (17 born preterm) with clinically diagnosed PHN and treated with iNO and 22 controls (14 born preterm). Three NO levels (10, 20, 40 ppm) were administered to the PHN infants to identify that associated with maximum oxygenation. Twenty-seven infants with PHN improved following iNO and had lower arginine levels than those infants who did not respond to iNO (p < 0.05). No significant relationship, however, was noted between the arginine levels and either the magnitude of change in the oxygenation index in response to iNO or the NO level associated with maximum oxygenation. The median plasma arginine level prior to iNO of the PHN infants was 12.5 (range 2–53) μmol/l, but not significantly lower than that of the controls (median 24, range 3–82 μmol/l). We conclude that differences in plasma arginine levels are unlikely to explain the variation in response to iNO and that, although arginine levels tended to be lower in infants with PHN, this is not a consistent finding in either the term or preterm infants.
Chronic Bradykinin Receptor Blockade Modulates Neonatal Renal Function
Authors: Tóth-Heyn Péter , Mosig Dolores , Guignard Jean-Pierre
Published: April 2003

Recent data indicate that bradykinin participates in the regulation of neonatal glomerular function and also acts as a growth regulator during renal development. The aim of the present study was to investigate the involvement of bradykinin in the maturation of renal function. Bradykinin β2-receptors of newborn rabbits were inhibited for 4 days by Hoe 140. The animals were treated with 300 μg/kg s.c. Hoe 140 (group Hoe, n = 8) or 0.9% NaCl (group control, n = 8) twice daily. Clearance studies were performed in anesthetized rabbits at the age of 8–9 days. Bradykinin receptor blockade did not impair kidney growth, as demonstrated by similar kidney weights in the two groups, nor did it influence blood pressure. Renal blood flow was higher, while renal vascular resistance and filtration fraction were lower in Hoe 140-treated rabbits. No difference in glomerular filtration rate was observed. The unexpectedly higher renal perfusion observed in group Hoe cannot be explained by the blockade of the known vasodilator and trophic effect of bradykinin. Our results indicate that in intact kallikrein-kinin system is necessary for the normal functional development of the kidney.
Vascular Potassium Channels Mediate Oxygen-Induced Pulmonary Vasodilation in Fetal Lambs
Authors: Mital Seema , Konduri G. Ganesh
Published: April 2003

The pulmonary vascular resistance decreases at birth secondary to release of endothelium-derived nitric oxide (EDNO). EDNO release is a calcium-dependent process, and endothelial potassium (K+) channels regulate intracellular calcium flux. We investigated the hypothesis that potassium channels mediate oxygen-induced pulmonary vasodilation and EDNO release in fetal lambs. We instrumented 18 near-term fetal lambs at 122–126 days of gestation to measure pulmonary pressures, flow, and resistance. We studied hemodynamic effects of (1) 100% oxygen; (2) pinacidil, an ATP-sensitive K+ (KATP) channel agonist, and (3) S-nitroso-N-acetylpenicillamine (SNAP), a NO donor. We studied the effects of glybenclamide, a KATP channel antagonist, tetraethylammonium chloride (TEA), a preferential KCa channel antagonist, and nitro-L-arginine (NLA), an NO synthase inhibitor, on the response to some of the above agents. Oxygen-induced pulmonary vasodilation was inhibited by both glybenclamide and TEA, indicating that KATP and KCa channels mediate pulmonary vasodilator response to oxygen. Blocking NO synthesis with NLA inhibited pinacidil-mediated pulmonary vasodilation, indicating that KATP channel activation stimulates NO release. SNAP-mediated pulmonary vasodilation was inhibited by TEA, but not glybenclamide, indicating that KCa channels, but not KATP channels, mediate effects of NO on vascular smooth muscle relaxation. In conclusion, K+ channels mediate oxygen-induced pulmonary vasodilation in fetal lambs. KATP channels appear to mediate EDNO release, while KCa channels probably mediate NO effects on vascular smooth muscle.
Essential Fatty Acids and Their Long-Chain Polyunsaturated Metabolites in Maternal and Cord Plasma Triglycerides during Late Gestation
Authors: Berghaus Thomas M. , Demmelmair Hans , Koletzko Berthold
Published: April 2003

The fatty acid composition of plasma lipids was determined in 41 pairs of mothers and their term infants at time of birth (38–42 postmenstrual weeks) by high-resolution capillary gas-liquid chromatography. Linoleic and α-linolenic acids were found at smaller concentrations in cord than in maternal triglycerides, in contrast to strikingly higher proportions of their long-chain polyunsaturated metabolites (LC-PUFA), which indicates a preferential maternofetal transport for certain physiologically important LC-PUFA. While no significant gestational age-dependent changes occurred in maternal plasma triglycerides, the values for most of the fetal long-chain n–3 metabolites increased with the duration of gestation, possibly reflecting an increased transplacental fatty acid passage during late pregnancy or a maturation of desaturation in the fetal liver.
Urinary Nitrite Excretion after Prophylactic Intravenous Immunoglobulin in Premature Infants
Authors: Özkan Hasan , Uzuner Nevin , Ören Hale , Çabuk Nur , İşlekel Hüray
Published: April 2003

Aims: To investigate the correlation between the prophylactic administration of intravenous immunoglobulin (IVIG) to preterm infants and urinary nitrite levels, which can be utilized as an index of endogenous nitric oxide (NO) formation, and to determine if NO formation plays a role in both therapeutic and adverse effects of IVIG. Methods: 28 healthy preterm infants were included in this prospective study. They had a mean gestational age of 29.4 ± 2.2 weeks and weight of 1,387 ± 371 g. Prophylactic IVIG infusion at a dose of 0.5 g/kg/day was administered when they were 3–10 days old. Urine samples of the neonates were obtained for analysis on days 1, 2 and 3 after IVIG administration as well as 1 day before. Urinary nitrite levels obtained in the subjects were normalized for urinary creatinine concentrations. Results: The mean urinary nitrite levels were: 2.77 ± 1.66 μmol/mmol creatinine before IVIG administration; 4.33 ± 3.88 μmol/mmol creatinine on the 1st day of IVIG; 3.77 ± 2.73 μmol/mmol creatinine on the 2nd day, and 3.64 ± 3.28 μmol/mmol creatinine on the 3rd day. There was a significant increase in urinary nitrite levels between before and after IVIG administration. There was no statistical difference in urinary nitrate levels between days 1, 2 and 3 after IVIG administration. Conclusion: We demonstrated that urinary nitrite excretion is significantly elevated in preterm infants after prophylactic IVIG administration and this result suggests that endogenous NO formation may play an important role in both the therapeutic and adverse effects of IVIG.
Endothelin Concentrations in Preterm Infants Treated with Human Recombinant Erythropoietin
Authors: Cogar Allison A. , Hartenberger Carol H. , Ohls Robin K.
Published: April 2003

Background: Increased endothelin-1 (ET-1) production following recombinant erythropoietin (Epo) administration is a presumed etiology for the hypertension reported in some adults. It is unknown whether Epo has similar effects in preterm infants. Methods: Serum ET-1 and Epo concentrations were measured prior to study, and following the second and third doses in 20 preterm infants receiving intravenous (IV) or subcutaneous (SC) Epo. Blood pressures were monitored prior to Epo administration and during the first, second, and third dose. Results: Infants (963 ± 54 g birth weight, 27.4 ± 0.6 weeks gestational age, 18 ± 3 days of life; mean ± SEM) had baseline Epo concentrations of 5.5 ± 1.3 mU/ml and ET-1 concentrations below the lower limits of detection (<1 pg/ml). Epo concentrations were 1,848 ± 274 and 1,672 ± 295 mU/ml following the second and third IV dose, respectively, while Epo concentrations were 420 ± 92 and 290 ± 35 mU/ml after the second and third SC dose, respectively (p < 0.005, SC versus IV). ET-1 concentrations remained below the limits of detection in all but 6 infants, whose concentrations were <3.3 pg/ml. Blood pressures did not increase above baseline in either group during the study period. Conclusion: Despite the wide range of Epo concentrations measured, no correlation was observed between Epo concentrations, ET-1 concentrations, and blood pressure during the 1-week study period. The long-term effects of Epo on ET-1 concentrations and blood pressure in preterm infants require further study.
Maturational Changes in Endothelium-Derived Nitric Oxide-Mediated Relaxation of Ovine Pulmonary Arteries
Authors: Kolber Keith A. , Gao Yuansheng , Raj J. Usha
Published: April 2003

Endothelium-derived nitric oxide (EDNO) modulates the responses of pulmonary vasculature. The present study was designed to determine EDNO-mediated responses of pulmonary arteries (PA) of term fetal, newborn, and adult sheep. Vessel rings were suspended in organ chambers and their isometric tension was recorded. In vessels preconstricted with endothelin-1, acetylcholine had no effect on fetal PA but caused a greater endothelium-dependent relaxation in adult PA than in newborn PA. In vessels without endothelium, nitric oxide and 8-bromo-cGMP caused greater relaxation in adult PA than in newborn PA while causing the least relaxation in fetal PA. Acetylcholine had no effect on cGMP content in fetal PA but caused a greater endothelium-dependent increase in cGMP content in adult PA than in newborn PA. In vessels without endothelium, nitric oxide caused a smaller increase in cGMP content of fetal PA than of newborn PA while causing the greatest increase in cGMP of adult PA. These results demonstrate an age-dependent increase in EDNO-mediated responses of ovine pulmonary arteries. A change in receptor and/or receptor coupling, in soluble guanylate cyclase activity, and in cGMP responsiveness of vascular smooth muscle may contribute to the phenomenon.
Effect of Fasting on Hepatic Lipase Activity in the Liver of Developing Rats
Authors: Peinado-Onsurbe Julia , Julve Josep , Galan Xavier , Llobera Miquel , Ramírez Ignasi
Published: April 2003

The effect of fasting on hepatic lipase was studied during postnatal development in the rat. It was found that fasting produced a significant decrease in hepatic lipase only in neonatal (1-day-old) and adult (60-day-old) rats. We studied the effect of fasting on the distribution of hepatic lipase between extracellular (heparin-releasable) and intracellular (liver-retained or residual) compartments in perfused livers, and on the secretion of hepatic lipase by isolated hepatocytes. Fasting had similar effects in neonates and adults: it decreased both the heparin-releasing and the residual activities in perfused livers, and also decreased the rate of hepatic lipase secretion by isolated hepatocytes. Finally, the effect of fasting on hepatic lipase mRNA relative abundance in developing rat livers was determined. No difference was observed among the groups studied. It is concluded that the mechanisms involved in the effect of fasting on hepatic lipase appear to be similar in neonates and adult animals and may involve the post-translational processing of the enzyme.
Heart Rate Variability in Preterm Brain-Injured and Very-Low-Birth-Weight Infants
Authors: Hanna B.D. , Nelson M.N. , White-Traut R.C. , Silvestri J.M. , Vasan U. , Rey P. Meleedy , Patel M.K. , Comiskey E.
Published: April 2003

Heart rate variability (HRV) reflects the complex interplay of the sympathetic and parasympathetic innervation of the heart. Developmental maturation of the fetus and newborn results in predictable alterations in the neural cardiac control of heart rate. Furthermore, patterns of HRV are closely correlated to clinical outcome in several pathologic situations. The first aim of this study was to characterize the maturational patterns of HRV in a group of developmentally at-risk newborns (those with severe hemorrhagic or ischemic brain injury and extremely immature, low-birth-weight infants). Secondly, we sought to determine whether a correlation exists between HRV and length of hospital stay, diagnosis of cerebral palsy, and neurodevelopmental test scores at 1-year corrected age. Time domain indices of HRV were computed longitudinally from 32 to 37 weeks of corrected gestational age in 19 very low birth weight, preterm infants. Among the 19 infants studied, 7 infants had no evidence of brain injury, 7 infants had periventricular leukomalacia (PVL), 3 infants had grade III/IV intraventricular hemorrhage (IVH), and 2 infants had both IVH and PVL. Neurologic injuries were documented using ultrasound and neurodevelopmental progress was followed through 1 year of corrected gestational age. A multivariate repeated measures analysis was performed to determine the relationship between the type of perinatal brain injury and neurodevelopmental status at 1 year of corrected gestational age. The type of perinatal brain injury was highly correlated to specific patterns of HRV with multivariate regression models producing adjusted r2 values ranging from 0.63 to 0.99. The type of perinatal brain injury was highly correlated to the developmental outcome measures (p < 0.0000) with PVL patients having the lowest neurodevelopmental scores, IVH patients having the highest scores, and noninjured infants having midrange, grossly normal values. Using ANOVA, HRV was correlated to outcome, but individual comparisons revealed statistical significance only for the noninjured group (p < 0.04). However, multivariate models, which characterized outcome within each brain injury group, were highly significant (adjusted r 2 ranged from 0.23 to 0.89). In summary, the type of perinatal brain injury determined the pattern of HRV and HRV was highly correlated to length of hospital stay and neurodevelopmental function assessed at 1 year of corrected gestational age.
Effect of Human Milk Fortifier on the Immunodetection and Molecular Mass Profile of Transforming Growth Factor-Alpha
Authors: Lessaris Karen J. , Forsythe Donna W. , Wagner Carol L.
Published: April 2003

Objective: To determine if the addition of human milk fortifier (HMF) affects the distribution, immunoreactivity, or molecular mass profile of transforming growth factor-α (TGF-α) within the compartments of human milk. Methods: Fifteen milk samples were obtained. Each sample was divided into two aliquots; a powdered HMF was added to the first aliquot. TGF-α concentration was measured via radioimmunoassay in whole milk and its aqueous and fat fractions ± HMF. TGF-α molecular mass profiles of the samples (v/v) were measured via Western blotting. Results: TGF-α concentration (mean ± SD) in fortified whole milk (15.7 ± 7.1 pg/100 μl) vs. nonfortified whole milk (14.8 ± 8.0 pg/100 μl) and in the aqueous fraction of fortified (14.0 ± 2.7 pg/100 μl) vs. nonfortified (14.0 ± 3.5 pg/100 μl) did not differ statistically. There was, however, a marked decrease in the concentration of TGF-α in the fat fraction of fortified (30.6 ± 2.8 pg/100 μl) vs. nonfortified (98.0 ± 6.9 pg/100 μl) milk samples. Western blot for TGF-α in whole milk and its separated fractions revealed characteristic bands at 6.5, 12–16, 22, 26–30 and 46 kD. HMF alone and HMF with sodium taurocholate had a prominent band at 18 kD and fainter bands at 6.5, 26–30, and 46 kD. While whole and aqueous milk samples with HMF also consistently showed the 18-kD band, in 8/15 fat fraction samples with HMF the 18-kD band was nondetectable and was only faintly detectable in the remaining 7/15 samples. Conclusions: It appears that HMF differentially alters the biochemical profile of human milk with regard to TGF-α concentration and molecular mass profile. What effect this alteration in human milk biochemistry has on neonatal gut function remains unknown.
Dihydrotestosterone Prevents Glucocorticoid-Negative Effects on Fetal Rat Metatarsal Bone in vitro
Authors: Picherit Christel , Coxam Véronique , Oudadesse Hassan , Martini Brigitte , Gaumet Nathalie , Davicco Marie-Jeanne , Lebecque Patrice , Miller Scott , Irrigaray Jean-Léon , Barlet Jean-Pierre
Published: April 2003

The effects of dihydrotestosterone (DHT) on glucocorticoid-pretreated fetal rat long bone were studied in an in vitro culture system. First, dose-response curves of corticosterone, hydrocortisone, and dexamethasone were studied at several concentrations. Then, hydrocortisone (H) at 10–5 M was selected for the second part of the study, as it slackened rudiment mineralization (104 ± 16% of the initial dark zone vs. 141 ± 9% in control bones), as well as its lengthening (140 ± 4% of the harvesting day length vs. 160 ± 1% in control bones), by both inhibition of cell proliferation and stimulation of resorption. On the contrary, in H-pretreated metatarsal bones, DHT (10–7 M) partly limited slackening of mineralization (124 ± 5%) and lengthening (153 ± 2%). Moreover, a control-like cell proliferation was re-established and resorption holes were filled in. Thus, in this study, DHT partly limited hydrocortisone-induced impairment of fetal rat metatarsal bone development.
Timing of Surfactant Administration Determines Its Physiologic Response in a Rabbit Model of Airway Lavage
Authors: Krause Martin F. , Hoehn Thomas
Published: April 2003

Surfactant response depends on timing of surfactant administration in infants with respiratory distress syndrome (RDS). We performed lung function studies in an animal model to describe the underlying differences in response related to gas exchange, lung volume and lung mechanics comparing early and late surfactant administration protocols. Young New Zealand rabbits were made surfactant deficient by repeated airway lavage with warm saline until the a/A O2 ratio decreased to ≤0.12. A natural ovine surfactant was administered at 1 h (early intervention) or at 3 h (late intervention) after the last lavage. Functional residual capacity (FRC), a/A O2 ratio, effective breath fraction (EBF = VA/VT), ventilation efficiency index (VEI), dynamic compliance (Crs), nitrogen clearing index (NCI) and specific (volumic) compliance (sCrs = Crs/FRC) were followed for 2 h after surfactant administration. FRC, a/A O2 ratio, VEI, Crs and sCrs were all significantly different between the two intervention groups in favor of the surfactant administration protocol at 1 h after lavage. EBF and NCI were not affected by timing of surfactant administration. We conclude that early surfactant administration elicits a superior response related to gas exchange, lung volume and lung mechanics in this animal model. These findings are in line with the more pronounced surfactant effects in the clinical setting when premature infants with RDS are treated using early intervention protocols.
Neonatal Blood Lymphocyte Subpopulations: A Different Perspective When Using Absolute Counts
Authors: de Vries E. , de Bruin-Versteeg S. , Comans-Bitter W.M. , de Groot R. , Hop W.C.J. , Boerma G.J.M. , Lotgering F.K. , Sauer P.J.J. , van Dongen J.J.M.
Published: April 2003

We compared the absolute counts of lymphocyte subpopulations in 15 neonates, and 9 adults using the whole lysed blood technique with 15 different triple immunostainings. To obtain accurate absolute lymphocyte counts in neonatal cord blood samples, the flow cytometric ‘lympho-gate’ was corrected for the erythroid cell contamination by normoblasts and unlysed erythrocytes. In contrast to earlier studies where relative frequencies were reported, we found that the major difference between neonatal and adult lymphocyte subpopulations concerned the much larger pool of naive ‘untriggered’ cells in neonates, standby for participation in primary immune responses.
Alterations in Fetal Adipose Tissue Leptin Expression Correlate with the Development of Adipose Tissue
Authors: Chen Xiaoli , Lin Ji , Hausman Dorothy B. , Martin Roy J. , Dean Roger G. , Hausman Gary J.
Published: April 2003

Control pig fetuses and fetuses hypophysectomized (hypox) at 70 days of gestation were treated with hormones on day 90. At 105 days of gestation, subcutaneous adipose tissue was prepared for morphological studies, leptin Northern blot and Western blot analysis. Fetal ontogeny studies showed that leptin mRNA in adipose tissue increased with morphological development, and the highest level of leptin mRNA was observed in 105-day fetal pigs. In hypox fetuses, levels of leptin mRNA were similar to those in controls. Treatment with either hydrocortisone (HC) or thyroxine (T4) resulted in a slight increase in leptin mRNA levels in hypox fetuses but not in intact fetuses. Supplementation with both HC and T4 markedly stimulated leptin mRNA expression in both hypox and intact fetuses. Morphological data showed that hypox slightly enhanced lipid accretion and treatment of hypox fetuses with HC and T4 increased lipid accretion to a greater degree than did either HC or T4 alone. However, serum leptin levels were not influenced by age, hypox or hormone treatment. Leptin protein expression was not detected in adipose tissue of hypox or intact fetuses regardless of hormone treatment. Leptin protein was detected in adipose tissue of 7-day-old pigs and placenta. As compared to 7-day postnatal adipose tissue, placenta showed a higher level of leptin protein expression. Leptin mRNA expression in fetal adipose tissue was not correlated with body weight and organ weight. The expression of long-form leptin receptor mRNA was detected in fetal adipose tissue. Our results indicate that adipose tissue leptin may not be the main source of serum leptin in the fetus and may not be involved in general prenatal growth and development. But adipose tissue leptin may act as an autocrine or paracrine factor in the development of fetal adipose tissue.
Bilirubin Oxidation by Brain Mitochondrial Membranes Is Not Affected by Hyperosmolality
Authors: Hansen Thor Willy Ruud , Allen Jeffrey W.
Published: April 2003

Brain mitochondrial membranes oxidize bilirubin at a rate that may be biologically significant. Hyperosmolality delays clearance of bilirubin from rat brain. We hypothesized that this might be due to a decrease in brain bilirubin metabolism. Rats were anesthetized and infused with 75 mM/kg urea i.v. over 5 min (n = 7) and sacrificed at 1 h; control rats (n = 7) had no treatment. Crude mitochondrial membrane fractions (‘P2’) were produced by homogenization and differential centrifugation in sucrose. The change in optical density at 440 nM of a 10-μmol/l bilirubin solution was measured after 60 min incubation with mitochondrial membranes. Hyperosmolality did not affect bilirubin oxidation by brain mitochondrial membranes (t = 1.27, p = 0.23 by unpaired t-test). The lack of effect of hyperosmolality on bilirubin oxidation by brain mitochondrial membranes suggests that decreased clearance of bilirubin from brain in hyperosmolality may be related to changes in transfer of bilirubin across the blood-brain barrier.
Endotracheal Measurement of Thyroarytenoid Activity in Newborn Lambs
Authors: Hutchison Alastair A. , Wozniak John A.
Published: April 2003

Laryngeal control of expiratory airflow is a principal means by which the newborn establishes and maintains absolute lung volume. Specifically, retardation of expiratory airflow is effected by the major adductors of the larynx, the thyroarytenoid (TA) muscles. The long-term aim of this research is to determine if monitoring TA activity can be used to optimize absolute lung volume during artificial ventilation of the human baby. This initial study, performed in unanesthetized chronically instrumented newborn lambs, tests the hypothesis that the timings of the onsets, peaks and durations of TA activity recorded by the endotracheal electrode are equivalent to those measured by a surgically placed intramuscular electrode. Endotracheal measurement of TA activity is accurate and specific and can monitor changes in airway pressure and lung volume.
Determination of Secretory IgA and Albumin in Saliva of Newborn Infants
Authors: Seidel Bastian Manfred , Schulze Birgit , Kiess Wieland , Vogtmann Christoph , Borte Michael
Published: April 2003

As a first line of defence against microbial invasion, secretory IgA (sIgA) is the dominant immunoglobulin on all mucosal surfaces. In this study sIgA was determined by radial immunodiffusion in saliva samples of 63 newborn infants divided into the following age groups: (1) 1 day and younger, (2) 2–10 days. Concentrations of sIgA and albumin as well as their relation to age, postprandial time, gestational age and birth weight were analysed. sIgA could be detected in 75.0% (group 1) and 77.1% (group 2) of the saliva samples with a mean concentration of 190.2 mg/l (group 1) and 216.4 mg/l (group 2). Differences failed to reach significance. Concentration of sIgA was found to be independent of age but positively related to the concentration of albumin in the same saliva sample. In conclusion, this study provides evidence that high levels of sIgA are found in saliva of newborn infants, indicating the existence of a competent oral mucosal immune system as early as within the first 10 days of life.
Use of Erythropoietin and Its Effects on Blood Lactate and 2,3-Diphosphoglycerate in Premature Neonates
Authors: Soubasi Vassiliki , Kremenopoulos George , Tsantali Chaido , Savopoulou Persefoni , Mussafiris Constantine , Dimitriou Maria
Published: April 2003

The aim of this study was to investigate the effect of recombinant human erythropoietin (rHu-EPO) on oxygen affinity and adequate oxygen delivery to the tissues of stable premature infants. 36 very-low-birth-weight infants were randomly assigned to either receive rHu-EPO (200 units/kg every other day) or not, and both groups were supplemented with iron, folic acid and vitamin E. Arterial blood gases, oxygen saturation, complete blood counts, fetal haemoglobin, 2,3-diphosphoglycerate (2,3-DPG) and blood lactate were analysed weekly, from the 1st week till discharge. Patients in the two groups were comparable. There was a trend in increasing lactate values towards the 4th to 5th weeks of life, which did not reach statistical significance. There was no correlation between lactate values and the studied variables (pH, BE, oxygen saturation). In 35 transfusions, pre- and 24 h post-transfusion blood lactate status was studied. In 23 of them, a decrease in post-transfusion lactate was noticed, whilst an increased post-transfusion level was shown in 10 cases and no change in 2 cases. The mean pre-transfusion lactate value was significantly higher than the post-transfusion one (24.04 ± 11.9 mg/dl before and 16.27 ± 8.5 mg/dl after transfusion; p = 0.0025). In both groups there was a steady rise in 2,3-DPG concentration over the period of study, and the 2,3-DPG values at the end of our study were significantly increased in the rHu-EPO group (rHu-EPO 5.98 ± 0.9, control 4.84 ± 0.7; p = 0.04). In conclusion, the use of rHu-EPO did not affect blood lactate levels compared to the control group. Regarding oxygen affinity, it seems that rHu-EPO causes a shift of the oxy-haemoglobin dissociation curve to the right. This is a previously unreported effect of rHu-EPO and its clinical use may, thus, confer to preterm babies an added advantage.
Suckling Dysfunction Caused by Defects in the Olfactory System in Genetic Arhinencephaly Mice
Authors: Hongo Takuya , Hakuba Akira , Shiota Kohei , Naruse Ichiro
Published: April 2003

Mouse newborns find their mother’s nipples and suckle milk by themselves. It has been argued which sense organ they use when locating their mother’s nipples to suckle milk. Olfactory or tactile sensory systems are primary candidates. In the present study, we investigated the trigeminal-whisker sensory and olfactory systems in genetic arhinencephaly mouse embryos (Pdn/Pdn). Pdn/Pdn newborns do not suckle milk and die within 1 day after birth. Dysfunction of nipple-searching behavior was clear in Pdn/Pdn newborns. Pdn/Pdn newborns had a complete developmental failure in the olfactory nerve projection to the central nervous system and no olfactory bulb architecture. The trigeminal-whisker system was intact in this strain. From the results of these experiments, it was suggested that the olfactory system is essential for nipple-searching behavior and suckling milk and that the trigeminal-whisker system is not able to substitute for the lack of olfactory input in mouse newborns.
Transcutaneous Absorption of Vitamin A in Newborn Rats
Authors: Ashmeade T.L. , Wiener D. , Barness L.A. , Carver J.D.
Published: April 2003

Very low birth weight neonates have low tissue concentrations of vitamin A, which may contribute to the development of lung disease. These infants, however, may not receive vitamin A supplementation for several days after birth. We determined if the relatively permeable skin of a newborn could be used to administer vitamin A. 25 control rat pups were killed and lungs and livers were collected. 20 μl (1,000 IU) of retinyl palmitate were applied to the skin surface of an additional 50 two-day-old pups. At 2.5 and 5 h after application, 25 pups were killed, and lungs and livers were collected. Concentrations of retinyl palmitate and retinol were significantly higher in the lungs of pups 5 h after administration of vitamin A compared with controls. There were no differences in concentrations of retinyl palmitate or retinol in livers. We conclude that transcutaneous administration may be an effective means of delivering vitamin A to the lungs of newborn rats.
EEG in Assessing Hydroxycobalamin Therapy in Neonatal Methylmalonic Aciduria with Homocystinuria
Authors: Bellieni C.V. , Ferrari F. , De Felice C. , Bagnoli F. , Cioni M. , Farnetani M. , Gatti M.G. , Buonocore G.
Published: April 2003

We performed serial electroencephalograms (EEG) in a newborn with methylmalonic aciduria and homocystinuria to assess the effects of hydroxycobalamin (OHcbl) therapy on the CNS. Diagnosis was made at 22 days of age: she had torpor, failure to thrive and hypotonia of the limbs, and intermittent opisthotonus. The first EEG, performed on the first day of therapy, showed abnormal and immature transients, low voltage and very long flat periods in the discontinuous part of the tracing. These features quickly improved during therapy. After 13 days of OHcbl therapy, the EEG tracing became normal for conceptional age and showed normal sleep phases with only minor anomalies; only mild hypotonia still remained and biochemical parameters normalized. The decrease in blood homocysteine (index of blood detoxification) was statistically correlated to the reduction of the length of flat periods in EEG (p < 0.01). In conclusion, changes in neonatal EEG, particularly the length of interburst periods in the intermittent part of the tracing, appeared to be a reliable index for evaluating drug effectiveness in methylmalonic aciduria and homocystinuria.
Advances in Peritoneal Dialysis: Towards Improved Efficacy and Safety
Authors: Krediet Raymond T.
Published: April 2003

Background: The success of peritoneal dialysis on the short-term is mainly dependent on the prevention of infectious and technical complications. The mid-term results will to a large extent be determined by the ability to remove enough uraemic toxins to prevent uraemic complications and malnutrition. The long-term challenge is the prevention of the development of structural abnormalities of the peritoneum leading to ultrafiltration failure and sometimes peritoneal sclerosis. Methods: A review of the literature on the possibilities to increase the removal of uraemic waste products from the body, and on strategies to detect and prevent deteriorations of the peritoneal membrane during long-term dialysis treatment. Results and Conclusions: Improved efficacy and safety of peritoneal dialysis on the midterm can be achieved by individualization of the dialysis prescription taking residual renal function especially into account. Early start of dialysis might reduce the progression rate of renal function deterioration, but exposes the peritoneum to bio-incompatible dialysis solutions for a longer time. The long-term alterations in the peritoneal membrane are probably mainly caused by the continuous exposure to dialysis fluids, especially glucose, and perhaps the combination of low pH with lactate. The implications of long-term continuous ambulatory peritoneal dialysis using only more biocompatible dialysis fluids are not clear. To improve the efficacy and safety of peritoneal dialysis, careful monitoring of patients and dialysis is mandatory. This should include 24-hour urine collections and 24-hour dialysate collections to calculate the residual glomerular filtration rate and adequacy parameters. A peritoneal membrane function test should be done regularly with 3.86% glucose dialysate, including determinations of dialysate Na+ and cancer antigen 125 to detect patients who are at risk for the development of structural abnormalities of the peritoneum.
Dialysis Hypersensitivity: A Fading Problem?
Authors: De Filippi Claudia , Piazza Valter , Efficace Emanuela , Galli Franco , Pisati Paolo , Aprile Carlo , Salvadeo Alessandro
Published: April 2003

Allergic-type reactions experienced by patients on chronic hemodialysis are frequently reported in the literature, often related to compounds released during the hemodialysis sessions, in particular ethylene oxide (ETO). In these studies, dialysis patients seem to have higher values of IgE than those observed in a reference population. The aim of our work was to investigate IgE-related parameters of 126 dialysis patients in comparison with two control groups composed of healthy subjects and predialysis patients. IgE values were not significantly different in nonallergic dialysis patients, with a geometric mean (X) of 27.5 kU/l, when compared to healthy controls (X = 38 kU/l) and predialysis subjects (X = 40.7 kU/l). Higher values of IgE (X = 74.1 kU/l) were detected in allergic dialysis patients. However, only 3 patients, all without detectable antibodies against ETO, complained of anaphylactic symptoms during dialysis sessions in a 4-year surveillance period. At variance, 6 symptom-free patients carried IgE antibodies against ETO (range 0.7–15 kU/l), usually with high total IgE. Our results suggest a reduced frequency of hypersensitivity reactions during dialysis sessions. Furthermore, uremia does not alter IgE reactivity in the predialysis period or after long-term maintenance dialysis treatment.
Effect of Prolonged Subcutaneous Implantation of Peritoneal Catheter on Peritonitis Rate during CAPD: A Prospective Randomized Study
Authors: Park Min Sun , Yim Ae Sook , Chung Sung Hee , Lee Eun Young , Cha Mi Kyung , Kim Jeong Ho , Song Kyung Il , Han Dong Cheol , Hwang Seung Duk , Moon Chul , Lee Hi Bahl
Published: April 2003

We conducted a prospective randomized controlled study to confirm our earlier observation that prolonged subcutaneous implantation of peritoneal catheter reduced peritonitis rate when compared to retrospective data from patients with catheters placed by conventional access technique. A total of 60 patients were randomized into two groups: 30 patients had catheters left implanted subcutaneously for 6 weeks (I) and the other 30 patients had catheters inserted by conventional technique and had 6 weeks of break-in period (C). Subgroups of 15 patients each with new and conventional techniques used Y-connector (IY, CY) and remaining patients used standard spikes (IS, CS).Mean age was 47.7 years (range 16–71); 61.0% were male and 44.1% diabetics. Peritonitis, exit site infection, simultaneous peritonitis and exit site infection, and complication related to Staphylococcus or Pseudomonas infections were observed for up to 2 years in each patient after initiation of bag exchange or until termination of CAPD by transfer to hemodialysis or by death.Total duration of observation was 493.2 patient-months for new access technique and 409.6 patient-months for conventional technique. Patients in IY group had the lowest incidence of peritonitis (1/14.9 patient-months) and exit site infection (1/16.8 patient-months) among four subgroups. Peritonitis rate in IY was significantly lower compared to CY or CS. The total peritonitis-free period in those patients who did not experience peritonitis during the observation period was also significantly longer in IY (120 patient-months) than in CY (26 patient-months), IS (10.6 patient-months), or CS (10.4 patient-months). Simultaneous peritonitis and exit site infection was observed in none of IY group but 3 episodes in CY, 4 episodes in IS, and 3 episodes in CS. The rates of complications related to Staphylococcus aureus and Pseudomonas infections were also significantly lower in IY than in CY, IS, or CS. Technique survival did not differ between the two groups.The present results confirm our previous observation that the new access technique reduces the incidence of peritonitis probably by reducing infection via periluminal route. The Y-connector system further reduces peritonitis rate by reducing infection via intraluminal route.
Hemoperfusion with Polymyxin B- Immobilized Fiber Attenuates the Increased Plasma Levels of Thrombomodulin and von Willebrand Factor from Patients with Septic Shock
Authors: Nakamura Tsukasa , Suzuki Yukiko , Shimada Noriaki , Ebihara Isao , Shoji Hisataka , Koide Hikaru
Published: April 2003

Aims: The present study assessed whether plasma levels of thrombomodulin and von Willebrand factor (vWF) are altered in patients with septic shock and whether treatment with polymyxin B-immobilized fiber (PMX-F) affects these levels. Methods: Twenty-four patients with septic shock and 20 normal healthy controls were included in this study. Plasma levels of thrombomodulin and vWF were measured by enzyme immunoassay (EIA). The treatments with direct hemoperfusion using PMX-F column on patients with septic shock were repeated twice for 2 h each. Healthy controls were not subjected to hemoperfusion. Results: 13 of 24 patients with septic shock survived (survival rate was 54.2%). Levels of blood endotoxin decreased significantly from 41.2 ± 4.8 pg/ml at baseline to 13.2 ± 3.6 pg/ml after direct hemoperfusion. Systolic blood pressure increased significantly from 82 ± 6 mm Hg at baseline to 118 ± 12 mm Hg after treatment. The patients with septic shock demonstrated significantly increased plasma levels of thrombomodulin (p < 0.001) and vWF (p < 0.001) compared with those in healthy controls. These increased levels of plasma thrombomodulin and vWF in patients with septic shock decreased significantly after treatment with PMX-F (p < 0.01). Conclusion: These data suggest that plasma thrombomodulin and vWF may be related to septic shock and that PMX-F is effective in reducing these factors in patients with septic shock.
A Case of McLeod Syndrome with Chronic Renal Failure
Authors: Jeren-Strujić Branka , Jeren Tatjana , Thaller Nikica , Živković Zoran , Raos Vjeka
Published: April 2003

A 50-year-old man with the rare McLeod syndrome, associated with glomerular lesion to the end stage of chronic renal failure and death, is reported. McLeod syndrome is an X-linked recessive disorder on the basis of abnormal expression of the Kell blood group antigens and absence of erythrocyte surface Kx antigen. Most often the clinical and pathological findings are retinitis pigmentosa to blindness, progressive chronic neuropathy, cortical atrophy, dilated cardiomyopathy, and glomerular lesion with chronic renal failure. Among the laboratory parameters the most important are very low level of cholesterol and triglycerides, then various numbers of acanthocytes in peripheral blood smears and sometimes in urine (as in our case).
Oxidative Protein Damage with Carbohydrates and Lipids in Uremia: ‘Carbonyl Stress’
Authors: Inagi R. , Miyata T.
Published: April 2003

Chronic uremia appears to be in a state of an increased oxidative stress. Under oxidative stress, proteins are modified directly by reactive oxygen species with the eventual formation of oxidised amino acids. Proteins are also modified indirectly with reactive carbonyl compounds formed by the autoxidation of carbohydrates and lipids, with the eventual formation of the advanced glycation/lipoxidation end products (AGEs/ALEs). AGEs, pentosidine and carboxymethyllysine (CML), and ALE, malondialdehyde (MDA)-lysine, are elevated in plasma and matrix proteins of uremic patients several times above normal subjects. Precursor carbonyl compounds derived from carbohydrates and lipids are indeed elevated in uremic circulation. Uremia thus appears to be in a state of carbonyl overload with potentially damaging proteins (carbonyl stress). Carbonyl stress might be relevant to long-term complications associated with chronic renal failure and dialysis, such as dialysis-related amyloidosis and atherosclerosis. Immunohistochemical studies identified carbonyl stress in long-lived amyloid deposits and vascular lesions. Proteins modified under carbonyl stress exhibit several biological activities, which might, at least in part, account for the development of joint and vascular complications in uremia.
Plasma C-Reactive Protein in Haemodialysis
Authors: Panichi V. , Migliori M. , De Pietro S. , Taccola D. , Metelli M.R. , Palla R.
Published: April 2003

In recent years, acute phase reactants have been reevaluated as not merely biochemical markers of inflammation but also as active modulators of the inflammatory response. C-reactive protein – which is normally present in serum in only trace amounts, but whose concentration may rise markedly with inflammatory stimuli – was the first human acute phase protein discovered. It is now clear that cytokines are the major mediators of acute phase protein induction: interleukin-6 currently is felt to be the principal cytokine influencing C-reactive protein acute changes. Several studies have provided convincing evidence that among normal men, base-line serum levels of C-reactive protein are predictive of future myocardial infarction and ischemic stroke. The relevance of acute phase reactants in morbidity and mortality of haemodialysis patients has not been fully elucidated until now: in fact a few studies have implicated C-reactive protein in malnutrition, EPO-resistance, as a cardiovascular risk factor and as a marker of chronic stimulation in haemodialysis. The authors suggest the hypothesis of the occurrence of long-term complications in patients exposed to contaminated dialysate and suggest that back-filtration may induce a chronic, slowly developing inflammatory state that may be abrogated by avoiding backfiltration of contaminated dialysate.
Fitness of Biocompatible High-Flux Hemodiafiltration for Dialysis-Related Amyloidosis
Authors: Takenaka Tsuneo , Itaya Yoshiaki , Tsuchiya Yoshitsugu , Kobayashi Kenji , Suzuki Hiromichi
Published: April 2003

Aims: In order to assess the long-term influence of high-flux hemodiafiltration (HDF) on hemodynamic stability in patients with dialysis-related amyloidosis. Methods: HDF with high-flux dialyzers was performed for a year in 11 patients who had undergone the surgery for carpal tunnel syndrome. Patients were divided into two groups, and for each group synthetic or cellulose membrane dialyzers were applied. Results: A year after the exchange from standard hemodialysis to HDF with cellulose high-flux dialyzers, β2-microglobulin was decreased (45 ± 3 to 28 ± 2 mg/l, n = 5, p < 0.05), but plasma non-refilling ratio was not altered. However, the continuance of synthetic high-flux HDF for a year decreased plasma non-refilling ratio (17 ± 5 to 7 ± 4%, p < 0.05), hypotensive episodes (4.3 ± 0.6 to 2.5 ± 0.4 sessions/month, p < 0.05) and muscle cramps (3.8 ± 0.5 to 1.8 ± 0.5 sessions/month, p < 0.01) in addition to the decrements in serum β2-microglobulin (45 ± 5 to 33 ± 2 mg/l, n = 6, p < 0.01). Conclusions: Although the study on a large number of patients may be required to draw a final conclusion, our present data suggest that biocompatible high-flux HDF is uniquely suited for dialysis-related amyloidosis.
Validation of a Simple Method for Assessing Sodium Intake in Dialysis Patients
Authors: Panzetta G. , Bianco F. , Ianche M. , Vianello S. , Vidi E. , Savoldi S. , Galli G. , Dal Moro A. , Klein P. , Zanchi R. , Cicinato P.
Published: April 2003

It has been reported that sodium intake can be estimated in dialysis patients by the increment in the body sodium pool from the end of a dialysis session to the beginning of the following one. To verify the reliability of this method we compared the sodium intake, estimated by the interdialytic changes in plasma sodium concentration (C) and body water volume (V), to sodium removal during three consecutive sessions. For this purpose we investigated 9 nondiabetic patients, 5 females and 4 males, under chronic hemofiltration treatment. Sodium intake was estimated by the formula (Cpre Vpre) – (Cpost Vpost) using a flame photometer and electrical bioimpedance to determine the plasma sodium concentration and total body water, respectively. Sodium removal was calculated by the difference between sodium loss into the ultrafiltrate and sodium gain with the reinfusion fluid. The mean values of sodium intake calculated during the three intervals corresponded with the sodium losses measured during the three hemofiltration sessions in each patient (338 ± 55 vs. 329 ± 67 mEq; r = 0.92, p < 0.0001). A direct relationship was also observed between sodium intake and both interdialytic body weight increase (r = 0.89, p < 0.0001) and fluid loss during the sessions (r = 0.88, p < 0.0001). This data demonstrates that sodium intake can be properly estimated by the interdialytic changes in body water and plasma sodium concentrations. They also suggest that fluid intake may be influenced by sodium consumption and that sodium intake monitoring could be useful for the control of excessive interdialytic fluid gain.
The gene-richest bands of human chromosomes replicate at the onset of the S-phase
Authors: Federico C. , Saccone S. , Bernardi G.
Published: April 2003

Previous investigations on the correlations between isochore organization and human chromosomal bands have identified three sets of R(everse) bands: H3+, H3* and H3–, endowed with large, moderate, and no detectable amounts of the gene-richest H3 isochores, respectively. In the present work we compared the replication timing of these three sets of bands and showed that the chromosomal bands containing H3 isochores replicate almost entirely (in the case of H3+ bands) or largely (in the case of H3* bands) at the onset of S phase, whereas chromosomal bands not containing H3 isochores (H3– bands) replicate later. The existence, at a resolution of 400 bands per haploid genome, of at least three distinct subsets of R bands is, therefore, not only supported by their GC and gene concentration but also by their replication times.