Normal Adult Values Research Articles

Reference values of NT-proBNP serum concentrations in the umbilical cord blood and in healthy neonates and children

N-terminal brain natriuretic peptide (NT-proBNP) is a neurohormonal substance secreted mainly by the cardiac myocytes of the left ventricle and to a less degree of the left atrium. The releasing mechanism is induced by an increased wall stress on the base of volume or pressure load of the ventricle. The physiologic actions of BNP are prohibition of the sympathetic activity, vasodilatation, natriuresis, diureses and inhibition of the renin-angiotensin system. Because of its high sensitivity and specifity in relation to the left ventricular incompetence, BNP as well as NTproBNP are well accepted markers of ventricular dysfunction. It was the aim of the study to establish reference values of NT-proBNP serum concentrations throughout childhood, in particular in the newborn age group. In a cross sectional study, serum NT-proBNP concentrations were measured by an ElectroChemiLuminescenceImmunoAssay ("ECLIA" Roche) in the umbilical cord blood of 62 healthy full-term neonates and in 222 healthy probands from birth up to the age of 18 years. The concentration of NT-proBNP in the cord blood samples ranged from 281 to 2595 pg/ml (mean: 818 pg/ml). There was a significant increase in the first days of life followed by a rapid decrease during the first year and a further gradual decrease throughout infancy; beyond the 10(th) year of age normal adult values were approached. The knowledge of the normal range of plasma NT-proBNP levels in healthy subjects during childhood serves as a non-invasive marker for differentiation of pathologic conditions such as acute myocarditis, hypertrophic or dilated cardiomyopathy, tachyarrhythmias and pulmonary hypertension.

Intestinal Absorption of Cholesterol by Patients with Smith-Lemli-Opitz Syndrome

The Smith-Lemli-Opitz syndrome (SLOS) is a disorder of impaired cholesterol biosynthesis because of a deficiency of the enzyme 7-dehydrocholesterol-Delta(7)-reductase, in the last step in cholesterol biosynthesis. Dietary cholesterol has been proposed as a potential therapy for SLOS and is being tested currently. Because there is no information on cholesterol absorption in SLOS, we recruited 12 SLOS patients into the General Clinical Research Center for 1-wk periods for administration of test meals and for blood and stool collections. A test breakfast that contained tracer cholesterol-4-C(14) with egg yolk or with crystalline cholesterol in suspension was given subsequently. Twenty-four and 48-h blood and 1-wk stool samples then were collected. The radioactivities in these samples were analyzed to determine the absorption of cholesterol by these patients. In 11 patients who were given egg yolk cholesterol, cholesterol absorption was 27.3 +/- 6.7%. The absorption was slightly less at 20.5 +/- 10.3% but not significantly different for the six patients who were given crystalline cholesterol. There was a positive correlation between the absorption of isotopic cholesterol as measured by determination of radioactive cholesterol in stool and the amount of isotopic cholesterol in the plasma at 24 and 48 h after the meal. Our data indicated that SLOS patients absorb cholesterol from the diet. However, the percentage of absorption is lower than reported values for normal adults and for hypercholesterolemic children. The absorption of crystalline cholesterol in suspension was slightly lower than the absorption of cholesterol in egg yolk cholesterol by these patients. The absorption of cholesterol may ameliorate some of the biochemical and developmental deficits in SLOS patients.

Onset and Pattern of Tear Secretions in Full-Term Neonates

Purpose: Serial evaluations of total, basal and emotional tear secretion in full-term normal neonates to determine the time after birth when these parameters attain normal adult values. Method: Both eyes of 102 full-term normal neonates were prospectively evaluated for tear secretions in the Department of Ophthalmology, over a period of one year. Serial recording of the Schirmer I test (total tear secretions), Basal Secretion Test, and Schirmer II test (emotional tears) was done, the first one being within 6 hours of birth. All the tests were repeated in each infant until normal adult values for each test were obtained. Results: The average values of the Schirmer I test, Basal Secretion Test and Schirmer II test at birth were 23.2 (± 3.96) mm, 6.2 (±2.15) mm and 19.2 (±4.94) mm, respectively. A statistically significant correlation of birth weight but not of gestational age was found with basal secretions (p = 0.004) as well as with emotional tears (Schirmer II test, p = 0.010). At birth, 98% of infants had total tear secretion, 3.9% had basal tear secretion and 2.9% had emotional tear secretion comparable to normal adult values. All the parameters of tear secretions increased with time, so that 100% of infants had total tear secretion comparable to normal adult values within 12 hours of birth. The basal secretions took three weeks and emotional tears took four weeks to attain normal adult values in all the neonates. Conclusion: Total tear secretions were the earliest to reach normal adult values, followed by basal secretions and, lastly, emotional tears. Reduced basal tears at birth may predispose neonates to corneal drying during prolonged ocular examinations such as indirect ophthalmoscopy and procedures under general anesthesia.

Concentrations of Pentosidine, an Advanced Glycation End-product, in Umbilical Cord Blood

Advanced glycation end-products (AGEs) are formed over several weeks to months by non-enzymatic glycation and oxidation (“glycoxidation”) reactions between carbohydrate-derived carbonyl groups and protein amino groups, known as the Maillard reaction. Pentosidine is one of the best-characterized AGEs and is accepted as a satisfactory marker for glycoxidation in vivo. The present study was intended to measure pentosidine concentrations in umbilical cord blood from newborns with various gestational ages using our recently established high-performance liquid chromatography method [Tsukahara, H. et al. (2003) Pediatr. Res. 54, 419–424]. Our study demonstrates, for the first time, that pentosidine is detected in most of the umbilical blood samples. This study also shows that the umbilical blood concentrations of pentosidine are considerably lower than normal adult values, but that they increase with gestation progression and fetal growth. Umbilical pentosidine concentrations were significantly elevated in newborns of mothers with preeclampsia compared to those of mothers without preeclampsia. We conclude that accumulation of AGEs and oxidative stress occurs in fetal tissues and organs in utero at the early stage of human life and that their accumulation is augmented in the maternal preeclampsic condition.

Book Reviews

Blood Cells, A Practical Guide, 3rd edn. Barbara J. Bain. Blackwell Science, 2001. 408 pp. £59·50. Once upon a time, long, long ago, bright and eager first-year medical students armed themselves with microscopes to begin their arduous journey. Over the next few painful years, they acquired other tools of the trade but, sadly, the once-revered microscope was relegated to a quiescent role of dust collection, superseded by stethoscopes and RT-PCR Tacman. As an old-timer haematologist who learned much haematology behind and through the eyepiece of my microscope, reviewing Dr Bain's Blood Cells, A Practical Guide was a refreshing return to a bygone era of microscopy which, as Dr Bain states in her preface, ‘not only provides the essential basis for our haematological practice, but can also lead to the excitement of discovery’. This book is aimed at the trainee in haematology and biomedical science as well as the clinical haematologist. It provides a comprehensive guide for the diagnostic clinical haematology laboratory and covers practical areas such as blood sample collection and preparation, performance of routine and more specialized laboratory tests and their clinical relevance and shortcomings. Much of this material is hard to find elsewhere. The piece de resistance/tour de force of this clearly written book is morphology, the forgotten art of haematology. The reader will find many pearls of wisdom scattered throughout the text. These nuances and practical tips are not usually in standard textbooks but are passed on from master to student in the course of patient care by doing, not reading (an example is how to find a good vein in a patient who has been through too many venepunctures). The author provides a detailed comparison of the available automated haematology instruments and offers important information on their unique strengths and weaknesses. The chapter on morphology is beautifully illustrated with photomicrographs of unusual clarity and consistency regarding magnification and staining characteristics. The completeness of the photomicrographs alone would provide enough material for a useful atlas of blood cells. Additional chapters present normal values in infants, children and adults, erroneous blood counts, quantitative changes in blood cells and important supplemental texts. The final two chapters review disorders of red blood cells, platelets and leucocytes, again comprehensively illustrated. Many tables throughout the text provide exhaustive lists of entities associated with specific morphological (e.g. spherocytosis) or clinical (e.g. splenomegaly) abnormalities. The student/trainee preparing for a board examination will find the quizzes after each chapter particularly useful. The multiple choice and extended matching questions are not easy and simulate the board examination in its most difficult, nastiest and meanest format. The coverage of tropical medicine is a bit more than the London or New York haematologist may need for his/her day-to-day clinical activities (25 illustrations of Plasmodium malaria in all its stages), but coverage of immunophenotyping, specific cytogenetic and molecular genetic abnormalities in leukaemias and lymphomas is a bit light. The reader is referred to a text published in 1999 for a more complete review of immunophenotyping, but rapid advances in the field would render a 1999 text somewhat obsolete. This edition contains many newer references. For example, in Chapter 8, 95/200 references (48%) were published since the first edition (1995). The many tables are well designed and complement the clearly written text. Some additional tables to consider for future editions might be (1) cytokine-associated morphological abnormalities; (2) histochemical differentiation of various leukaemias; and (3) cytogenetic and molecular genetic findings in different lymphomas and leukaemias. One would hope to see important new data on molecular genetic profiling and gene arrays in leukaemias, lymphomas and myeloproliferative/myelodysplastic disorders, an area that will drive therapeutic strategies in these entities in the near future. Dr Bain's measure of success for her book was to send ‘the reader back to the microscope with renewed interest and enthusiasm’. With this third edition of a gem of a text, she has succeeded brilliantly. This book will find a useful place on the bookshelf right above the haematologist's trusty microscope.

Measurement of peritoneal fluid pH in patients with non-serosal invasive gastric cancer.

The accurate pH range of peritoneal fluid is clinically valuable for the evaluation of some pathological conditions of the body, however, it is not easy to measure in healthy individuals. The aim of this study was to measure; pH, pCO2, pO2, Na+, K++, Ca++, HCO3-, and O2 saturation of the peritoneal fluid in patients with non-serosal invasive gastric cancer. One hundred and thirty four patients (86 men and 48 women), ranging in age from 24 to 91 years were enrolled in this study. After opening the abdominal wall, the probe of a portable pH meter was placed in the peritoneal fluid in the subhepatic space. In addition, I collected the peritoneal fluid from the subhepatic space to measure, pH, pCO2, pO2, Na+, K++, Ca++, HCO3-, and O2 saturation using an autoanalyzer. The pHs of the peritoneal fluids tested has a mean of 7.73 (range 7.46 - 8.10), and the other parameters were pCO2, 22.81 mmHg; pO2, 136.49 mmHg; Na+, 146.57 mmol/L; K++, 4.80 mmol/L; Ca++, 0.89 mmol/L; HCO3-, 30.54 mmol/L, and O2 saturation, 99.74%. This study describes a practical method of measuring the pH of peritoneal fluid. The result obtained reflects the normal adult peritoneal pH value, which I propose as a reference value.

Vasoactive and natriuretic mediators in umbilical cord blood: a report of our observation and review of the literature.

The relative potency and interrelationship among vasoactive and natriuretic mediators are thought to be important in the transition from fetal to neonatal life. However, little is known about their potential roles in the perinatal setting. The aim of this study was to evaluate further the potential roles of vasoactive and natriuretic mediators in the perinatal setting. We measured umbilical venous levels of arginine vasopressin, endothelin-1, adrenomedullin, natriuretic peptides and NO(2)(-)/NO(3)(-) in 24 vaginally delivered newborns and examined their possible functions. Cord levels of vasopressin, endothelin-1 and adrenomedullin were considerably higher compared with normal adult values; the concentrations were more than 10-fold higher for vasopressin, and more than threefold higher for endothelin-1 and adrenomedullin. The levels of natriuretic peptides and NO(2)(-)/NO(3)(-) were almost comparable to those of normal adults. Among the mediators, there was a significant correlation between endothelin-1 and adrenomedullin. It appears from other studies that the postnatal fall in vasopressin and endothelin-1 levels is associated with increased levels of natriuretic peptides and NO(2)(-)/NO(3)(-). Based on these observations, we consider that these mediators may play active roles in the initiation, maintenance or both of the transition from fetal to neonatal life.

Variations of nasal nitric oxide in a subject with allergic rhinitis: A longitudinal study

Purpose: Nitric oxide (NO) in the exhaled air is mainly produced by the upper respiratory airway mucosa, and the output of NO has been found to differ from normal in sinonasal disease. In allergic rhinitis (AR) nasal NO output (VNO) has been reported to increase compared with healthy individuals. The purpose of this study was to observe daily variations in VNO in a subject with AR and to investigate the effect of environmental factors on VNO. Material and Methods: We measured VNO daily in an individual with AR over a period of 5½ months to determine the variability of VNO from day to day. We used a 41-year-old, nonsmoking volunteer with AR as our subject to investigate the relationship between VNO and some environmental factors likely to affect VNO. The correlation between VNO and nasal symptom scores was also investigated. Daily ambient NO concentrations, humidity, atmospheric pressure, and atmospheric grass pollen concentrations were recorded along with morning nasal NO measurements. At each measurement session, online NO measurements were done from both nostrils at 5 L/min constant transnasal flow. During the study the subject had a short period of a cold and a short period of purulent rhinitis and started using a nasal steroid spray at the end of the study. Results: VNO levels for our subject were higher than previously published values for normal and allergic adults. There was an increase in VNO (the highest value throughout the study) in the prodromal period of the cold and a significant decrease (the lowest values throughout the study) during the cold. Change during the purulent rhinitis was less remarkable than change during the cold. Conclusion: No correlations between environmental conditions (humidity, atmospheric pressure, pollen count) and VNO were found. VNO changes were also independent of specific and cumulative nasal symptom scores. (Am J Otolaryngol 2002;23:191-195. Copyright 2002, Elsevier Science (USA). All rights reserved.)

Uroguanylin level in umbilical cord blood.

Uroguanylin is a novel natriuretic and diuretic peptide originally isolated from urine. To determine whether uroguanylin has a physiologic role during the perinatal period, uroguanylin levels in umbilical cord plasma obtained at the time of delivery were measured by radioimmunoassay and compared with cord serum osmolality. Mean (+/- SD) cord plasma uroguanylin concentrations (8.8 +/- 2.1 fmol/mL) were higher compared with normal adult values. The extent of maturity, mode of delivery and gender did not appear to influence cord uroguanylin levels. The uroguanylin concentration had a significant positive correlation with cord serum osmolality. These findings support some regulatory role of this peptide in perinatal renal and cardiovascular adaptation.

Longitudinal stability of visual evoked potentials in children and adolescents with hydrocephalus.

There were two purposes for this study: to determine the within-subject changes of visual evoked potentials (VEPs) over time, and to evaluate the usefulness of baseline VEP testing in the early diagnosis of increased intracranial pressure (ICP). Twenty children with hydrocephalus between the ages of 4 and 18 years (18 males, 2 females) were evaluated monthly for up to four months. Flash-evoked VEP tests were done in a standardized manner using a Cadwell Quantum 84 evoked potential stimulation and recording instrument. One participant had abnormal VEPs found during a previous episode of shunt malfunction. For all of the other VEP tests, the latency of the N2 response was in the range of adult normal values. For 15 participants with multiple evaluations there were non-significant differences in N2 latency from one session to the next. This study's results provide evidence that within-subject VEP measurements in children with hydrocephalus appear to be relatively stable over limited periods. However, considerable differences were found when comparing VEPs between participants. Further research may provide additional evidence that periodic, routine VEP testing is an effective way to monitor individuals who have shunted hydrocephalus in order to detect increased ICP before the appearance of obvious symptoms.

Implant‐supported overdentures, a prevention of bone loss in edentulous mandibles?

The purpose of this study were to analyse 1) the changes in the bone mineral content (BMC) in mandibles with implant-supported overdentures when compared with the physiologic age-related mandibular BMC loss, 2) whether the BMC changes were different in groups without or with a bar connecting the implants and 3) whether the presence of mandibular osteoporosis affects the loss of bone height around the implants. The material consisted of 22 long-term edentulous healthy persons, 18 women and 4 men from 54 to 78 years of age with 1 Astra Tech Dental Implant in both canine regions, connected by a bar in half of the patients. BMC measurements were performed in vivo by dual-photon scanner at baseline, just after attachment insertion, at 2-year and 5-year visits. Mandibular osteoporosis was estimated by comparing baseline BMC values with normal mandibular BMC values for young adults of same gender. Loss of bone height around implants was measured on periodically identical intraoral radiographs. The fixed parts of the implant-system were stable during the trial in all patients. 1) the increased function after this treatment seems to cause a load-related bone formation which minimizes the physiologic age-related mandibular BMC loss, 2) this effect seems to be independent of attachment system and 3) mandibular osteoporosis prior to implant treatment may be a risk factor for bone loss around implants. However, this treatment can be recommended also in osteoporotic persons.

Longitudinal stability of visual evoked potentials in children and adolescents with hydrocephalus

There were two purposes for this study: to determine the within‐subject changes of visual evoked potentials (VEPs) over time, and to evaluate the usefulness of baseline VEP testing in the early diagnosis of increased intracranial pressure (ICP). Twenty children with hydrocephalus between the ages of 4 and 18 years (18 males, 2 females) were evaluated monthly for up to four months. Flash‐evoked VEP tests were done in a standardized manner using a Cadwell Quantum 84 evoked potential stimulation and recording instrument. One participant had abnormal VEPs found during a previous episode of shunt malfunction. For all of the other VEP tests, the latency of the N2 response was in the range of adult normal values. For 15 participants with multiple evaluations there were non‐significant differences in N2 latency from one session to the next. This study's results provide evidence that within‐subject VEP measurements in children with hydrocephalus appear to be relatively stable over limited periods. However, considerable differences were found when comparing VEPs between participants. Further research may provide additional evidence that periodic, routine VEP testing is an effective way to monitor individuals who have shunted hydrocephalus in order to detect increased ICP before the appearance of obvious symptoms.

Knowledge about pulse oximetry among residents and nurses

EDITOR: Pulse oximetry has become a monitoring standard for anaesthesia and intensive care [1,2]. Knowledge of the basic principles, clinical and technical considerations, as well as an understanding of the oxyhaemoglobin dissociation curve is important [3-5]. We decided to evaluate how well medical and nursing personnel - who use pulse oximetry - understood it and their ability to interpret the information. A 17-item multiple choice questionnaire was prepared. The questions consisted of seven demographic items related to: place of work, years of experience in the use of pulse oximetry, and adequacy of training in pulse oximetry. The remaining 10 questions tested the knowledge of pulse oximetry. The topics and results are given in Table 1. Participation was voluntary and anonymous. Having agreed, the subjects were interviewed on the same day precluding any preparation.Table 1: Percentage of correct answers to the different questions Twelve residents and 44 nurses (comprising the total complement of staff in the ICU) completed the questionnaire and their responses were scored against answers obtained from standard reference texts. The response rate was 100%. The participants' experience is shown in Table 2. All residents had some degree of anaesthesiology training. Thirty-five of the nurses came from various surgical intensive care units (anaesthetic, neurosurgical, cardiovascular, general surgical intensive care units) and nine nurses were from a medical (neurological) intensive care unit. Although most (98%) used pulse oximetry regularly in their daily work, only 14% believed that they had had adequate training yet 70% felt sufficiently confident in using pulse oximetry. Half of them had 1-3 years of experience at work.Table 2: Duration of employment of residents and nurses The residents and nurses who believed they had received adequate education about pulse oximetry had worked for more than 3 years in their present job. We think that residents received instruction by the attending staff anaesthesiologists when pulse oximeters were originally introduced into routine clinical practice in this hospital. Subsequently, residents must have learned to interpret the findings of pulse oximetry by themselves or from their more senior colleagues. None of the nurses had received any formal education on this topic. Elsewhere first year residents also scored fewer points in a survey [6]. Although most of the participants (75%) knew what a pulse oximeter measures, only 14% understood its technological principles. Five of the 12 residents and four of the 44 nurses answered correctly. In a study by Kruger and Longden, six of 33 residents and one of 164 nurses answered correctly [7]. The questions concerning the relationship between PaO2 and SpO2 proved rather difficult; only two residents (4%) answered correctly. In the above mentioned study, 15 of the 33 residents and three of the 164 nurses knew the correct answer [7]. This suggests that the oxyhaemoglobin dissociation curve needs to be taught and explained in more detail. It should be stressed that when the value of SpO2 is 90%, PaO2 is approximately 60 mmHg. However, 43% of participants identified normal values for SpO2 and 54% of the participants recognized those for PaO2. Seventy-one per cent of the participants could explain why no reading is obtained if the patient had a cardiac arrest and how decreasing oxygen saturation would be observed after a respiratory arrest. Eighty per cent of the participants knew where the sensor (light probe) should be attached and 63% knew that there are different probes for adults and children. The normal saturation ranges for adults were identified by 19% and by 32% for children. Possibly more attention is paid to children or the participants perceive that there is a wider spectrum of normal values in adults [6]. The lower limit of reliability was incorrectly given as less than 70% SpO2 by 59% of the respondents (we took 85% as the correct answer). However, 14% of the participants could only name one factor, which may affect the accuracy of a pulse oximeter, whereas 86% were able to name two or more factors. The choice of factors included: hypothermia, poor peripheral perfusion (vasoconstriction or hypotension), problems with the light probe, nail polish, arrhythmia, shivering, or bright extraneous illumination, as taken from the responses in another study [8]. Hypothermia was most commonly indicated; peripheral vasoconstriction, hypotension, and disconnection of the probe were the other answers given in this study. The high proportion of incorrect answers indicating low knowledge levels could in some circumstances lead to more careful follow-up of patients due to misinterpreted alarms but would cause unnecessary alerts of anaesthetists or perhaps lead to inappropriate procedures. Other studies also show insufficient knowledge in less experienced staff [6]. More emphasis should be placed on teaching the principles of pulse oximetry with regular updates for the new recruits. H. BILGIN O. KUTLAY D. CEVHEROGLU G. KORFALI Department of Anesthesiology and Intensive Care Unit, Uludag University School of Medicine, Bursa, Turkey

The analysis of the complement activation product SC5 b-9 is applicable in neonates in spite of their profound C9 deficiency.

Native complement factors and complement activation products were measured in healthy neonates (n = 72) and in a group of infants with premature prolonged rupture of the membranes (PPROM) without sepsis (n = 10). Vitronectin concentration in normal cord blood was not correlated with gestational age, and the median value was 86.0% of adult values. This was markedly higher than other native complement factors studied (factor B: 35.9%, C4: 45.1%, C3: 56.2%). The concentration of C9 showed a positive correlation with gestational age and was very low, 10.8% of normal adult values in cord blood and 8.3% in the patients. Fifteen percent of the neonates had C9 levels lower than 2% of adult values. The complement activation products Bb and SC5 b-9 were significantly elevated in the patients (159% and 130% of control values, respectively), indicating alternative and terminal pathway activation. In contrast, C4 bc and C3 bc levels were not increased. The maximum amount of SC5 b-9 which could be generated in the neonatal sera by cobra venom factor was highly correlated with C9 concentration (rs = 0.86, p = 0.0001) The profound C9 deficiency found in neonates is correlated with gestational age, limits the capacity to form bacteriolytic C5 b-9 (m) and may predispose for severe invasive bacterial infection. The plasma level of SC5 b-9 under normal conditions was very low, only 0.3% (0.1%-3.0%) of the values obtained after CVF activation of the same samples. Therefore, we suggest that the analysis of SC5 b-9 is applicable also in neonates, in spite of their extremely low C9 levels.

Normal adult values, diurnal variation, and repeatability of nasal nitric oxide measurement.

Reports of elevated nasal nitric oxide (NO) levels in allergic rhinitis suggest that nasal NO levels could be a valuable marker of upper airway inflammation, provided that the reproducibility of nasal NO measurement is acceptable. The aims of this study were to evaluate the precision with which nasal NO levels can be measured at single point in time, and to quantify within-day and between-day variation. Nasal NO was measured using a modified chemiluminescence analyzer. Population data were normally distributed, as judged by testing for skewness and kurtosis. NO levels were not related to age or gender, and there was no evidence of diurnal variation. Sampling rates of 250 mL/minute and 500 mL/minute at a single point in time had acceptable reproducibility (coefficients of variation 10.2% and 6.6%, respectively). However, within-day variation (coefficient of variation 13.4%) and between-day variation (coefficient of variation 11.8%), at a sampling rate of 500 L/minute, were substantially higher. These findings highlight the importance of taking measurement variation into account, in the interpretation of NO levels, in clinical research and, potentially, in routine practice. In individual patients, an alteration of 20-25% in NO levels is required, to ensure that change is genuine and not ascribable to the noise of measurement.

Elevated Cytokines and Cerebral Palsy

Neurology| September 01 1999 Elevated Cytokines and Cerebral Palsy AAP Grand Rounds (1999) 2 (3): 30–31. https://doi.org/10.1542/gr.2-3-30 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Elevated Cytokines and Cerebral Palsy. AAP Grand Rounds September 1999; 2 (3): 30–31. https://doi.org/10.1542/gr.2-3-30 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: cerebral palsy, cytokine, interferons Source: Grether JK, Nelson KB, Dambrosia JM, Phillips TM. Interferons and cerebral palsy. J Pediatr. 1999;134:324–332. In a retrospective study, Grether et al investigated the association between spastic cerebral palsy (CP) and serum levels of neonatal interferons (IFNs), other inflammatory cytokines, thyroid hormones, complement and coagulation factors. The subjects were selected from a population based case-control study of CP risk factors conducted in the San Francisco area between 1983 and 1985. One hundred and ninety-two children were identified with CP at 3 years of age. From this group, a subset of children with moderate to severe spastic CP was selected based upon the availability of archived blood from newborn metabolic screening and neonatal exposure to intrauterine infection, asphyxia or maternal problems in the second half of pregnancy. Also included was a small group of children with no apparent cause for their CP. The final study cohort included 31 mostly term children with spastic CP for whom neonatal blood spots were available, and 65 children of unknown gestational age and weight randomly selected from the control group. Blood was eluted from blood spots that had been stored over time at −15°F and analyzed for various constituents. Fourteen of the 31 children with spastic CP were found to have levels of all 3 IFNs higher than any child in the control group and were at or above the maximum adult normal values. IL-1, 6, 8, TNF alpha and other inflammatory mediators were also high in this group. In contrast, thyroid hormones, total T4, T3 and complement proteins C3, 4 and 9 were lower than in the controls. Seven of the 9 children with increased IFNs had spastic diplegia, a subtype of CP. In the remaining 17 of the cases, IFNs were low and in the range observed in the control group. The concentration of other cytokines, thyroid hormones and complement were also within the normal range. Although these children with CP had no evidence of inflammation, 70% of them had one or more coagulation factors that were abnormal. The most frequent form of CP in this group was spastic hemiplegia. The etiology of CP remains elusive in the majority of children. Recently, strong epidemiological evidence has been presented linking maternal intrauterine infection with neonatal white matter disease or periventricular leukomalacia (PVL) in the preterm infant. Yoon reported a correlation between elevated cytokines in amniotic fluid, histologic chorioamnionitis, PVL on neurosonography and CP.1 In children who died with PVL, immunohistochemical studies have shown an overproduction of cytokines in hypertrophic astrocytes and microglial cells of the CNS.2,3 Sixty to 100% of neonates with PVL develop CP, most commonly spastic diplegia. Cytokine mediated inflammatory reactions appear to be involved in the evolution of brain damage. In this small (N=31) retrospective exploratory study, Grether et al found that nearly half of the 31 children with CP had evidence of inflammation during the neonatal period with markedly elevated serum IFNs and other inflammatory mediators. This is the first report... You do not currently have access to this content.

Urinary oxalate and urate to creatinine ratios in a healthy pediatric population

The purpose of the study was to determine reference percentiles for the urinary (U) oxalate (Ox) and urate (Ura) to creatinine (Cr) concentration ratios in the second morning urine of healthy infants, children, and adolescents. The urinary oxalate and urate to creatinine ratios were determined in the spontaneously voided second morning urine sample. To test reproducibility, two urine samples were analyzed on 2 consecutive weeks in 63% of the subjects. Three hundred eighty-four healthy children (181 girls, 203 boys), aged 1 month to 17 years, from nurseries, kindergartens, and schools of Lausanne, Switzerland, were studied. The 5th and 95th percentiles were determined from the total number of urine samples (627) after confirmation that there was no order effect between repeated measurements and there were no significant sex differences. A nonlinear regression analysis in terms of age was used to smooth the calculated percentiles. In this manner, curves were obtained from which the reference values can be read at any given age. The 95th percentiles decreased with age: for UOx/Cr from 0.175 mg/mg (0.22 mol/mol) at 1 to 6 months to 0.048 mg/mg (0.06 mol/mol) from 7 years and beyond; and UUra/Cr from 2.378 mg/mg (1.6 mol/mol) at 1 to 6 months to 0.594 mg/mg (0.4 mol/mol) in adolescence. We provide 5th and 95th percentile curves for the UOx/Cr and UUra/Cr ratios determined from the second morning urine samples in a large cohort of healthy infants, children, and adolescents. Values were determined by standard analytical chemical techniques and were analyzed by powerful statistical methods. The calculated 95th percentile for the UOx/Cr values fell rather rapidly and reached normal adult values by the age of 7 years, whereas for UUra/Cr, the 95th percentile decreased slowly and stabilized in adolescence.

Primary HIV infection of infants: the effects of somatic growth on lymphocyte and virus dynamics.

Acute HIV infection is characterized by the appearance of high concentrations of virus in the peripheral blood. In adults, this high-level viremia spontaneously abates after several weeks. In contrast, after perinatal infection of infants, blood virus levels remain high for many months, during which the concentration of circulating CD4+ lymphocytes remains well above normal values for adults. Here we suggest an explanation for these differences, based on developmental factors including somatic growth and immunological ontogeny. Flow cytometric analysis revealed that at birth the thymus contains elevated levels of mature T lymphocytes, compared to the thymus after 3 months of age. A mathematical model is proposed incorporating immunological and virological data from longitudinally evaluated infants who acquired infection at the time of birth. This model explains the pattern of high-level viremia in infants as resulting from the replication of HIV within the progressively expanding lymphoid cell mass.

Reevaluation of the relaxed calcaneal stance position. Reliability and normal values in children and adults.

Reliability and normal values for the relaxed calcaneal stance position were determined in a nonclinic population of healthy adults and children (88 adults and 124 children) ranging in age from 5 to 36 years. The mean relaxed calcaneal stance position for adults was 6.07 degrees valgus (SD 2.71 degrees) (range, 1 degree varus to 14 degrees valgus). The mean relaxed calcaneal stance position for children was 5.6 degrees valgus (SD 2.9 degrees) (range, 6 degrees varus to 12 degrees valgus). There was no significant difference between the relaxed calcaneal stance positions of adults and children. In children the relaxed calcaneal stance position did not correlate with age, height, or weight and did not decrease with age to the theoretical normal value of 0 degree +/- 2 degrees as postulated by Root et al. The relaxed calcaneal stance position was found to be a reliable measurement; however, the theoretical normal value of 0 degree +/- 2 degrees was not found. The values reported in the present study correspond with the results of other empirical studies; thus the theoretical normal value for the relaxed calcaneal stance position of 0 degree +/- 2 degrees may be invalid.

Developmental changes in brain serotonin synthesis capacity in autistic and nonautistic children.

Serotonin content, serotonin uptake sites, and serotonin receptor binding measured in animal studies are all higher in the developing brain, compared with adult values, and decline before puberty. Furthermore, a disruption of synaptic connectivity in sensory cortical regions can result from experimental increase or decrease of brain serotonin before puberty. The purpose of the present study was to determine whether brain serotonin synthesis capacity is higher in children than in adults and whether there are differences in serotonin synthesis capacity between autistic and nonautistic children. Serotonin synthesis capacity was measured in autistic and nonautistic children at different ages, using alpha[11C]methyl-L-tryptophan and positron emission tomography. Global brain values for serotonin synthesis capacity (K complex) were obtained for autistic children (n = 30), their nonautistic siblings (n = 8), and epileptic children without autism (n = 16). K-complex values were plotted according to age and fitted to linear and five-parameter functions, to determine developmental changes and differences in serotonin synthesis between groups. For nonautistic children, serotonin synthesis capacity was more than 200% of adult values until the age of 5 years and then declined toward adult values. Serotonin synthesis capacity values declined at an earlier age in girls than in boys. In autistic children, serotonin synthesis capacity increased gradually between the ages of 2 years and 15 years to values 1.5 times adult normal values and showed no sex difference. Significant differences were detected between the autistic and epileptic groups and between the autistic and sibling groups for the change with age in the serotonin synthesis capacity. These data suggest that humans undergo a period of high brain serotonin synthesis capacity during childhood, and that this developmental process is disrupted in autistic children.