bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone mineralization after treatment of growth hormone deficiency in survivors of childhood malignancy
Authors: Nussey SS , Hyer SL , Brada M , Leiper AD
Published: January 2008

Having noted symptomatic osteoporotic vertebral collapse in young adult survivors of childhood malignancy, bone mineral density (BMD) was examined at three sites by dual‐energy X‐ray absorptiometry in 64 patients treated in childhood for intracranial malignancy (group 1; n = 21) or acute leukaemia (group 2; n = 43). Patients in group 1 were selected for growth hormone deficiency (GHD) by auxological and biochemical criteria before the end of puberty (Tanner stage V). Seven patients (six men; mean (± SEM) age at study, 28.0 ± 2.9 years; mean age at diagnosis, 8.7 ± 1.5 years) in this group had been treated with human pituitary growth hormone (GH) for 1–12 years; and 14 patients (nine men; mean age at study, 26.8 ± 1.0 years; mean age at diagnosis, 10.7 ± 1.4 years) had not received GH. Bone densities in group 1 were normal in the GH‐treated patients at the femoral neck (98.4 ± 3.8% of control), lumbar spine (100.4 ± 6.1% of control) and Ward's triangle (101.0 ± 6.1% of control) but markedly reduced in the untreated group (femoral neck, 81.2 ± 2.6% of control (p= 0.002); lumbar spine, 79.1 ± 4.1% of control (p= 0.04); Ward's triangle, 80.1 ± 3.6% of control (p= 0.01)). The majority of patients in group 2 had been treated for acute lymphoblastic leukaemia (ALL) and were in three subgroups. Fifteen (ten men; mean age at study, 22.1 ± 0.8 years; mean age at diagnosis, 5.7 ± 0.8 years) had no auxological evidence of GHD, ten (six men; mean age at study, 18.8 ± 0.7 years; mean age at diagnosis, 6.6 ± 1.2 years) received GH therapy for a mean of 2.6 years (range, 0.5–5.0 years), while 14 patients (three men; mean age at study, 20.9 ± 0.4 years; mean age at diagnosis, 5.1 ± 0.8 years) had GHD but did not receive GH. A small group of four patients (three men; mean age at study, 23.2 ± 2.1 years; mean age at diagnosis, 8.0 ± 2.3 years) who had been treated for acute myeloid leukaemia (AML) in childhood was also studied. The patients with AML had normal bone densities at all three sites (femoral neck, 106 ± 6.1% of control; lumbar spine, 96.5 ± 3.0% of control; Ward's triangle, 110.8 ± 9.3% of control), as did the patients with ALL who did not have GHD (femoral neck, 102.3 ± 2.9% of control; lumbar spine, 98.6 ± 1.7% of control; Ward's triangle, 108.3 ± 3.2% of control). The patients with ALL and GHD not treated with GH had markedly reduced BMD at all three sites (femoral neck, 90.5 ± 2.6% of control; lumbar spine, 88.4 ± 2.5% of control; Ward's triangle, 94.5 ± 3.7% of control), but those treated with GH had a BMD no different from control (femoral neck, 100.6 ± 3.3% of control; lumbar spine, 95.7 ± 4.6% of control; Ward's triangle, 106.2 ± 4.9% of control). It is concluded that GHD during childhood and adolescence predisposes to osteopenia.
Effects of insulin‐like growth factor I treatment on the molecular distribution of insulin‐like growth factors among different binding proteins
Authors: Gargosky SE , Wilson KF , Fielder PJ , Vaccarello MA , Diamond FB , Baxter RC , Rosenbloom AL , Guevara‐Aguirre J , Rosenfeld RG
Published: January 2008

The molecular distribution of insulin‐like growth factor I (IGF‐I) and IGF‐II among the IGF binding proteins (IGFBPs) was studied before and during IGF‐I therapy in Ecuadorean adults with growth hormone receptor deficiency (GHRD). Of the total circulating IGF‐I and IGF‐II, 70% was carried by the 150 kDa complex in normal subjects, while in patients with GHRD, 50% of serum IGF‐I, but only 30–35% of serum IGF‐II, was measured within the 150 kDa IGFBP‐3 region. Administration of IGF‐I altered the concentration of IGF‐I and IGF‐II, although the percentage of total IGF measured within each IGFBP region was not affected, as the increase in IGF‐I and the decrease in IGF‐II were proportional. Similarly, serum concentrations of IGFBP‐3 and the acid‐labile subunit, measured by radioimmunoassay, were unaltered. Thus, administration of IGF‐I to patients with GHRD was unable to correct the aberrant distribution of IGFs among the IGFBPs.
The global HIV pandemic
Authors: Stoneburner Rand L , Sato Paul , Burton Anthony , Mertens Thierry
Published: January 2008

The paper reviews the distribution, transmission patterns, and likely impacts of the HIV pandemic at the beginning of 1993. As of early 1993, a cumulative total of 611,589 cases of AIDS were reported to the World Health Organization (WHO); however, because of less than complete diagnosis and reporting, the WHO estimates that a total of 2.5 million cases of AIDS had actually occurred. As of early 1993, the WHO estimates that there have been approximately 13 million infections, of which about 1 million have been in children. By the year 2000 the WHO predicts that there will be 30–40 million cumulative infections in the world, of which 90% will be in developing countries and almost half will be among women. The epidemic of HIV infection in the decade of the 1980s will result in an epidemic of AIDS in the 1990s, which will place great social and economic strains on many countries, particularly those in many areas of the developing world.
Epidemiology of HIV infection in children in Italy
Authors:   The Italian Register for HIV Infection in Children
Published: January 2008

As of April 1992, 2337 children born to HIV‐1‐positive mothers were recorded by our multicentre study. Another 131 children were infected by contaminated blood products, while in 5 cases the risk factor remained unknown, as their personal history was lacking. The number of perinatally exposed children increased exponentially from 1981 to 1986, then stabilized. Of these, at last visit 624 were infected (531 P‐2, 93 P‐1), 463 were P‐O and 1195 had seroreverted. Drug addiction continues to be the most frequent maternal risk factor, although infection acquired through sexual contact gradually increased up to 26.5% in 1991. Of the 762 first children identified at birth and older than 15 months of age, 132 (17.3%) acquired infection and seroconverted to HIV. A similar transmission rate was observed in 43 second‐born children.
Human Immunodeficiency Virus type 1 infection and breast milk
Authors:   The Italian Register for HIV Infection in Children
Published: January 2008

Major questions are whether mothers infected with the Human Immunodeficiency Virus type 1 (HIV‐1) transmit the virus through breast milk and the magnitude of the additional transmission risk. The demonstration of a dose‐response effect is an epidemiological method to demonstrate causality. Thus, a study was carried out by the Italian Register for HIV Infection in Children on 961 children of known infection status. Duration of breast‐feeding was considered as the level of exposure in 168 ever breastfed children. Results showed that duration of practice significantly increased the risk of transmission. The adjusted infection odds ratio for one day of breast‐ versus exclusive formula‐feeding was 1.19 with narrow confidence limits (1.10–1.28). In a second study by the Register on 556 children of known infection status and derived prospectively, an infection odds ratio of 2.55 (confidence interval: 1.03–6.37) was calculated in breast‐ versus exclusively formula‐fed children. Several lines of evidence, including the above‐mentioned data from the Italian Register for HIV Infection in Children, showed a contribution of breast‐feeding to mother‐to‐child HIV‐1 transmission. Thus, this practice is now discouraged in HIV‐1 infected mothers living in industrialized societies where formula feeding is practical and attainable. Mode of feeding was known in 2183 children enrolled in the Register and born to HIV‐1 infected mothers since 1981. It could be observed that feeding habits of at‐risk infants changed in Italy in the middle 1980s, when a large majority of subjects was identified at birth. However, women infected exclusively by the sexual route are often unconscious of being infected or even being at risk from infection and consequently their children are less frequently identified at birth than are children of women with a history of intravenous drug use. In industrialized areas, the former children remain at risk from milk‐borne HIV‐1 infection.
Behavioral risks for HIV in adolescents
Authors: Moss N
Published: January 2008

A psychosocial perspective on adolescent risk behavior is used to highlight aspects of psychological development and social environment that are relevant to sexual activity and substance use. Differences in behavior are also related to factors such as age and gender that have biological, developmental, and demographic implications. Sexual activity and substance use increase during adolescence, and are often interrelated. In the USA in 1992, 69% of 8th graders and 88% of 12th graders had drunk alcohol. In 1990, 54% of high school students had had sexual intercourse. Age of sexual initiation has decreased in recent cohorts, but condom use by adolescents has increased, with 35% of 15–19‐year‐old women reporting using condoms. Interventions that successfully change adolescent risk behavior take account of the teen's level of development and social context.
Adolescents and HIV infection: A clinician's perspective
Authors: D'Angelo Lawrence J
Published: January 2008

Increasing concern in the United States has centered on HIV infection in adolescents. While less than 0.4% of all reported cases of AIDS are reported in adolescents 13–19 years of age, it is speculated that upwards of 20% of all AIDS cases have acquired their infection as teenagers. Most cases are now reported to occur among minority youth and most are now related to sexual or drug use behavior. The natural history of HIV infection in adolescents has yet to be defined. Many adolescents have progressed to clinically significant low CD4+ cells by the time their infection is discovered. While traditional risk factors are also risk factors for adolescents, number of sexual partners and non‐injection drug use appear to be related to an increased risk of HIV infection in this age group. Prevention efforts must target both techniques as well as one‐on‐one counselling. Health care providers have a unique role to play in both patient and community education.
Protein nutrition, faecal flora and iron metabolism: the role of milk‐based formulae
Authors: Wharton BA , Balmer SE , Berger HM , Scott PH
Published: January 2008

This paper explores the role of milk‐based formulae in achieving four aspects of nutritional health in infants and toddlers: in the suckling, to mimic the amino acid metabolism and the faecal flora of a breast‐fed baby; in the weanling, to achieve adequate protein intakes in later infancy and beyond and to achieve satisfactory haemoglobin concentrations in the early toddler years. Milk‐based formulae have two roles in infant nutrition: as so‐called breast milk substitutes and as a safety net during the weaning period; the latter role may be the more important.
Follow‐on formulae
Authors: Toro R Di
Published: January 2008

Follow‐on formulae are recommended as part of the liquid intake of the weaning diet for infants from 6 months on and children aged 12–36 months. The amount of energy and nutrients absorbed by infants from Beikost and milk differs enormously depending on a number of factors and therefore the recommended composition of follow‐on formulae varies accordingly. In the future a greater understanding of the nutritional needs of infants and the possibility of choosing between high‐ or low‐protein content formulae may provide infants with a better balanced diet.
Fat needs of term infants and fat content of milk formulae
Authors: Giovannini M , Agostoni C , Riva E
Published: January 2008

Term infants have precise dietary fat requirements for their metabolic, energy and structural needs. The fat content of commercial milk formulae differs from maternal milk in that it contains no long‐chain polyunsaturated derivatives or cholesterol. Artificially fed children thus have less of these molecules available for their biological needs, and hence lower levels of long‐chain polyunsaturated derivatives in circulating and membrane lipids than breast‐fed children. The functional effects of this difference have not been investigated thoroughly in term infants. Dietary lack of essential fatty acids and their derivatives is evident also in weaned children during the second half of their first year of life. Qualitative changes in the fat content of commercial milk formulae could help to correct some widely encountered dietary imbalances, using the pattern of fats provided in breast milk as the ideal.
Essential fatty acids and human tissue composition. An overview
Authors: Ballabriga A
Published: January 2008

Essential fatty acids act as a structural fat and play an important role during the period of organ growth during fetal and postnatal life. Given the essential character of these fatty acids, their qualitative and quantitative intake and their interrelations contribute to the maintenance of different functions during the period of human development. The structural integrity of the cell membranes depends on the composition and total content of long‐chain polyunsaturated fatty acids (LCPUFAs) of the membrane phospholipids. These LCPUFAs act as modular regulators of the permeability and fluidity of the membranes, are precursors of eicosanoids, may influence membrane enzymes and may affect signal transduction, neurotransmission and transport activities (1–4). The lipid composition of cellular membranes can change in relation to the LCPUFA supply, which is fundamentally that coming from the diet, thus influencing the growing tissues of different organs, although to varying degrees.
Children of alcoholics: Attention, information processing and event‐related brain potentials
Authors: van der Stelt O , Gunning WB , Snel J , Zeef E , Kok A
Published: January 2008

Recent studies on biological markers and risk factors for alcoholism have distinguished between nonalcoholic individuals with a family history of alcoholism and those without such a family history on measures of event‐related brain potentials. The main finding of these “high‐risk” studies is a smaller amplitude of the P300 component in males with a history of paternal alcoholism. This relationship between P300 amplitude and a family history of paternal alcoholism has been observed in adults and children. Consequently, several authors have suggested that a reduced P300 amplitude could serve as a vulnerability marker for alcoholism. We address several conceptual and methodological issues involved in the study of event‐related potentials in children at high risk for alcoholism. Subsequently, the ongoing high‐risk study of the Amsterdam Institute for Addiction Research is described briefly.
Development after prenatal exposure to cocaine, heroin and methadone
Authors: van Baar AL , Soepatmi S , Gunning WB , Akkerhuis GW
Published: January 2008

In Amsterdam a longitudinal, prospective and multidisciplinary study on the development of infants of drug‐dependent mothers (IDDM) was started in 1983: 35 IDDM and 35 reference infants were originally enrolled. The drug‐dependent women had used combinations of methadone, heroin, cocaine and other drugs during pregnancy. Of the IDDM, 80% had to be treated pharmaceutically for neonatal abstinence symptoms (NAS). Physical, neurological, cognitive and the socio–emotional development of the children were studied regularly from birth until 5.5 years of age. Differences between the reference group and the IDDM were found most clearly in cognitive development. The IDDM also had more behavioural problems at some of the ages studied. No group differences were seen in motor development. So far the results of the study show that IDDM and their caregivers need extra support in order to improve early communication and the children's cognitive development.
Red blood cell fatty acid composition in low‐birth‐weight infants fed either human milk or formula during the first months of life
Authors: Chirouze V , Lapillonne A , Putet G , Salle BL
Published: January 2008

The fatty acid composition of red blood cell (RBC) phospholipids in low‐birth‐weight infants was determined immediately after delivery and during the first 3 months of life. In the first study, infants were fed either human milk or two formulas with different fatty acid compositions but no long chain polyunsaturated fatty acids (LCPUFA). Both groups of formula‐fed infants had significantly lower levels of docosahexaenoic acid (DHA) in RBC phospholipids compared with breast‐fed infants. RBC phospholipid DHA was similar in the two formula groups at all ages. In the second study, infants received either a non‐supplemented or a LCPUFA‐supplemented formula. DHA remained stable in RBC phospholipids of infants supplemented with LCPUFA, whereas DHA decreased in RBC phospholipids of unsupplemented infants. These results confirm that adding DHA to formulas is more effective than increasing 18:3 n‐3 content, in maintaining RBC phospholipid DHA levels.
Metabolic balance studies and plasma amino acid concentrations in preterm infants fed experimental protein hydrolysate preterm formulas
Authors: Rigo J , Senterre J
Published: January 2008

The aim of this study was to investigate absorption and retention of nitrogen, fat, calcium, phosphorus and magnesium, as well as plasma amino acid concentrations in 19 preterm infants fed three experimental protein hydrolysate preterm formulas (PTHF): seven received a preterm formula based on 100% whey hydrolysate protein (PTHF1), seven other infants were fed a preterm formula based on a mixture of 78% whey and 22% casein hydrolysed protein (PTHF2) and a third group of five infants were fed the same type of protein hydrolysate (78/22) enriched with histidine (PTHF3). Metabolic balances (n= 39) and plasma amino acid concentrations (n= 12) in preterm infants fed a standard preterm formula (whey/casein: 60/40) were included as a control group. Amino acid composition of the formulas was determined after complete hydrolysis with 12 N HC1. Compared with the standard preterm formula, the use of protein hydrolysate formulas led to a decrease in nitrogen and phosphorus absorption without modification of retention. Net absorption of calcium and magnesium was not significantly different in the four groups but calcium intake necessary to obtain calcium retention similar to the standard preterm formula was higher in the infants fed the hydrolysate formulas. Plasma amino acid concentrations were related to the amino acid composition of the formulas. Compared with the standard preterm formula, all three protein hydrolysate formulas led to a significant increase in plasma threonine, and a decrease in tyrosine and phenylalanine concentrations. In addition, there was an important reduction in plasma histidine concentrations with PTHF1. This was partly corrected with PTHF2. Similar values that in the control group were only obtained with PTHF3 enriched in histidine. However, with this latter formula, low plasma concentrations of tryptophane and cystine were observed. This study suggests that the nutritional adequacy of preterm protein hydrolysate formulas need to be investigated before they can be proposed for routine use in preterm infants.
Assessment of bone ages by the Tanner‐Whitehouse method using a computer‐aided system
Authors: Drayer NM , Cox LA
Published: January 2008

A computer‐aided system to estimate bone age based on Fourier analysis was assessed by reference to the original radiographs used to produce the Tanner‐Whitehouse 2 (TW2) standards for the radius, ulna and short finger bones. The computer‐aided system involved matching a template of each bone to the scanned image of the radiograph. The computer then generated a stage of bone maturity, individual and total bone scores and a value for bone age. The bone ages assessed by the computer‐aided system were no different from the original TW2 reference values, indicating the applicability of the system. The system was used to assess the bone ages of tall Dutch girls, and the results obtained were compared with more traditional assessments made by an experienced rater. For the radiographs from the tall girls, there was good agreement for individual bones between this method and the traditional assessment by the rater, but less agreement for the total 13‐bone score and bone age.
Preliminary report on the validation of a grammar‐based computer system for assessing skeletal maturity with the Tanner‐Whitehouse 2 method
Authors: Cox LA
Published: January 2008

A series of hand and wrist radiographs was assessed manually by two individuals and by a fully automated computer system for determining bone age. Assessments were repeated after 1 month to determine variability between and within the methods of bone age assessment. There was slight intra‐observer variation, but complete reproducibility when assessments were made by computer. The variation between the human assessors was less than that between human and computer assessments. The difference between overall maturity scores made by the human observer and the computer system was, however, acceptably small, and the majority of assessments were the same. It is concluded this computer system for assessing bone age in normal children is reliable and accurate, but that it needs to be validated against a much larger set of radiographs.
Characterization of growth hormone binding sites in rat brain
Authors: Zhai Q , Lai Z , Roos P , Nyberg F
Published: January 2008

The binding of 125I‐labelled rat growth hormone (GH) to different areas in the brain was studied in male Sprague‐Dawley rats. A high density of GH binding was found in the choroid plexus, hypothalamus, hippocampus, pituitary and spinal cord, whereas a lower binding density was observed in the cortex. Binding of the hormone to the various brain regions was age dependent. Binding was also dependent on time, pH and protein concentration. The binding affinity of the labelled hormone to choroid plexus was 4.3 per nmol/l and the binding capacity was 33.4 nmol/mg protein. The corresponding figures for binding of 125I‐labelled GH to hypothalamus were 5.6 per nmol/1 and 21.6 nmol/mg protein. By sodium dodecyl sulphate electrophoresis of the cross‐linked hormone‐receptor complexes, molecular weights of 60,000 and 61,000 were determined for the binding units in the choroid plexus and hypothalamus, respectively. It was further indicated that the binding unit for rat GH was distinct from that for prolactin.
Mutations in the phenylalanine hydroxylase gene: methods for their characterization
Authors: Guldberg P , Güttler F
Published: January 2008

Mutations in the phenylalanine hydroxylase (PAH) gene represent the root cause of PAH‐deficient hyperphenylalaninemia. To date, more than 160 different mutations have been reported. Single‐base substitutions and microdeletions account for the majority of molecular defects. This review provides a brief general introduction to various strategies for detection of PAH mutations, and summarizes our own methodological developments. We have established a method based on PCR in combination with denaturing gradient gel electrophoresis (DGGE) for mutation scanning of the entire coding sequence and all exon/intron boundaries of the PAH. Systematic application of this method to the study of a large number of mutant chromosomes from hyperphenylalaninemic patients demonstrated a 98% diagnostic efficiency and a 100% mutation detection efficiency. We have created compromised PCR and DGGE conditions for simultaneous amplification and simultaneous mutation scanning of all PAH‐coding fragments. This technique is convenient in a diagnostic setting and allows “same‐day” DNA‐based diagnosis of newborns with hyperphenylalaninemia. A further modification of the method allows unambiguous identification of known mutations, circumventing the cumbersome step of nucleotide sequencing.
Spectrum and origin of phenylketonuria mutations in Spain
Authors: Pérez B , Desviat LR , Lucca M De , Ugarte M
Published: January 2008

In order to characterize the molecular heterogeneity of phenylalanine hydroxylase deficiencies in the Spanish population, 37 PKU patients were initially screened for 16 known European mutations. For the remaining unidentified alleles, we used a combined strategy based on single strand conformation polymorphism analysis and DNA sequencing. Overall, a total of 15 different mutations were found in our sample, which account for 62% of the total mutant alleles. We also investigated the association between the mutations, haplotypes and variable number of tandem repeats described on the phenylalanine hydroxylase gene. In addition, we analyzed the geographical distribution in Spain of the two most prevalent mutations in our population: IVS10 and I65T.
Automated sequencing detects all mutations in Northern Irish patients with phenylketonuria and mild hyperphenylalaninaemia
Authors: Zschocke J , Graham CA , Stewart FJ , Carson DJ , Nevin NC
Published: January 2008

In the first phase of the Northern Ireland PKU Study, we used automated sequencing to identify the spectrum of mutations in a random group of 32 unrelated phenylketonuria (PKU) families. We also investigated 7 Northern Irish patients with mild hyperphenylalaninaemia not requiring dietary intervention (MHP, previously referred to as non‐PKU HPA). Disease‐causing mutations were identified on all 78 investigated chromosomes. We found 23 different mutations, including 20 missense, 1 nonsense and 2 splice site mutations. All mutations were located within exons or at intronexon boundaries of the phenylalanine hydroxylase gene. Seven mutations occurred at CpG sites, confirming these sites as mutation hot‐spots in PKU. Mutations R408W and I65T are the two commonest PKU mutations in the Northern Irish population. Two mutations (T380M and V245A) can be characterized as MHP mutations; they are quasi dominant markers for MHP since they cause mild hyperphenylalaninaemia even when occurring in conjunction with the most severe PKU mutations. The results have proven valuable for the development of a routine PKU mutation analysis system in Northern Ireland.
Mutations in the phenylalanine hydroxylase gene: genetic determinants for the phenotypic variability of hyperphenylalaninemia
Authors: Güttler F , Guldberg P
Published: January 2008

Phenylalanine hydroxylase (PAH) deficiency is heterogeneous disease at the phenotype level. The spectrum of clinical and metabolic phenotypes spans from the potential pathogenic disease classical phenylketonuria (PKU) to the benign condition non‐PKU hyperphenylalaninemia (non‐PKU HPA). This review provides an introduction to the clinical variants of PAH deficiency, and summarizes our attempts to define the disease at the molecular level and to relate mutation genotype to clinical outcome. Complete genotype determination in a large number of patients with PAH‐deficient hyperphenylalaninemia demonstrates that clinical heterogeneity can be explained by a multiplicity of mutations in the PAH gene. Some combinations of mutations are associated with phenylalanine levels fluctuating around the border between PKU and non‐PKU HPA. However, certain mutations seem always to cause non‐PKU HPA irrespective of the mutation on the second allele and can, therefore, unambiguously be designated as being associated with the non‐PKU HPA phenotype. Our results suggest that mutation analysis in newborns presenting with hyperphenylalaninemia can be used for rapid and highly efficient differential diagnosis of PAH deficiency, and for predicting the severity of the disease. These possibilities may facilitate and optimize the management of hyperphenylalaninemia and thereby improve prognosis.
Indications of changed amino acid homeostasis in untreated and treated PKU
Authors: Hjelm M , Seakins J , Antoshechkin A
Published: January 2008

Amino acid patterns were investigated in children with untreated and treated phenylketonuria (PKU) and compared with hospitalized paediatric control group. Correlation ratios, i.e. the ratio between the number of statistically significant correlations between pairs of amino acids, were calculated and found to be 0.125, 0.331 and 0.35 in the three groups. Link ratios, i.e. the frequency of statistically significant correlations between particular amino acid and other amino acids, varied between 0.00 and 0.18, 0.06 and 0.56, and 0.18 and 0.59 in the same groups. Link ratios for especially isoleucine, histidine and arginine were decreased in treated PKU compared to the control group. A reverse non‐linear relationship was established between decreased plasma phenylalanine induced by dietary treatment and increased threonine in plasma. These findings indicate that amino acid homostasis is disturbed in untreated PKU and not fully normalized in treated patients. The clinical relevance of the findings is unknown.
Review of neuropsychological functioning in treated phenylketonuria: an information processing approach
Authors: Waisbren SE , Brown MJ , de Sonneville LMJ , Levy HL
Published: January 2008

Phenylketonuria is no longer associated with mental retardation and other devastating neurological effects. Nonetheless, learning disabilities and IQ loss are common, even in early‐treated individuals. Until recently, IQ was used as the sole measure of mental functioning in this population. As specific academic deficits were recognized and as greater variety of tests became available, evaluation of children with phenylketonuria has included neuropsychological testing. A review of the 21 published reports highlights the areas of consensus and the need for additional well designed studies in the future. Problem solving, particularly abstract reasoning and executive functions, appears to be impaired in children with phenylketonuria. Reaction time, or speed of mental processing, appears to be the other important area affected in PKU. An information processing model is presented as paradigm for further research and development of remedial strategies for children with phenylketonuria.
Information processing deficits in children with early and continuously treated phenylketonuria?
Authors: Stemerdink BA , van der Molen MW , Kalverboer AF , van der Meere JJ , Hendrikx MMT , Huisman J , van der Schot LWA , Slijper FME
Published: January 2008

Thirty‐three patients with early and continuously treated classical phenylketonuria (PKU) and 33 controls matched for age, gender, and educational level of both parents, participated in chronometric study exploring elementary mechanisms of information processing. Subjects performed speeded performance tasks designed to systematically vary the load on perceptual, central, and output‐related mechanisms of information processing. A preliminary analysis of the data indicated that the overall performance of patients with early and continuously treated PKU practically matched that of the controls on all three tasks. Although this finding must be interpreted with caution as it is based on only preliminary analysis of the data, it suggests that PKU patients who are continuously maintained on a well‐controlled phenylalanine‐restricted diet are not deficient in the elementary mechanisms of processing. Given the more recent findings indicating that young children with early‐treated classical PKU have specific cognitive deficits in the executive function skills, despite relatively strict dietary control, the authors suggest that future studies should focus on these higher‐order cognitive processes.
The PKU mouse project: its history, potential and implications
Authors: McDonald JD
Published: January 2008

To produce genetic‐based animal models for the human disease phenylketonuria (PKU), we treated mice with the powerful germline mutagen ethylnitrosourea and screened the progeny of these animals for the symptom hyperphenylalaninemia (HPH). Six independent mutant strains have been produced to date that exhibit heritable HPH. The first mutation isolated was found to cause a reduced level of GTP‐cyclohydrolase I activity and, as such, yields a model for tetrahydrobiopterin‐dependent HPH. The next two mutations have yet to be fully characterized but cause syndromes that appear distinct from any PKU or HPH syndromes yet reported for humans and they are allelic. Next we isolated a mutation that caused a marked reduction in hepatic phenylalanine hydroxylase activity levels. The enzyme deficiency was not sufficient to cause a PKU syndrome but instead produced a mild HPH syndrome. This strain played an instrumental role, however, in the identification of two additional mutant strains that appear to model human PKU very accurately in the laboratory mouse. These latter strains have levels of HPH very similar to human PKU patients, exhibit a phenylalanine‐dependent hypopigmentation, and have reproductive difficulties that resemble human maternal PKU.
Renal Osteodystrophy in Children Treated with 1,25‐Dihydroxy‐Cholecalciferol [1,25‐(OH)2D3]: Histologic Bone Studies
Authors: ROBITAILLE PIERRE , MARIE PIERRE J. , DELVIN EDGARD E. , LORTIE LOUISE , GLORIEUX FRANCIS H.
Published: January 2008

ABSTRACT. Eleven uremic children with osteodystrophy aged 3 to 17 years were studied during administration of l, 25‐(OH)2D, for periods up to 21 months. Nine children presented with pure hyperparathyroidism, one with osteomalacia and one with mixed bone disease. Bone biopsies were performed before initiation of therapy and after 6 to 21 months of treatment following double tetracycline labeling. Skeletal lesions were improved but not cured in 5 of 9 children with hyperparathyroidism. In three instances lesions remained unchanged and worsened in one. No significant change was observed in the child with osteomalacia. Moderate improvement was noted in the patient with mixed bone disease. The propensity to develop hypercalcemia was the major factor associated with treatment failure since it precluded administration of adequate amounts of medication. Therapy with l, 25‐(OH)2D3 was associated with a spectacular improvement in growth velocity in two of six children under age twelve.
Immunoreactive Copper‐Zinc Superoxide‐dismutase (SOD‐1) in Mosaic Trisomy 21 and Normal Subjects
Authors: BAETEMAN M. A. , MATTEI M. G. , BARET A. , MATTEI J. F.
Published: January 2008

ABSTRACT. Copper‐zinc superoxide‐dismutase (SOD‐1) (E.C. 1.15.11) levels were measured in 9 children with mosaic trisomy 21 as identified by R, H, G‐banding technics. Radioimmunoassay of erythrocytes and fibroblasts did not demonstrate any significant correlation between levels of SOD‐1 and percentage of trisomic 21 cells in the two target cell populations studied.
Plasma Proinsulin and C‐Peptide Concentrations in Children with Hyperinsulinaemic Hypoglycaemia
Authors: AYNSLEY‐GREEN A. , JENKINS P. , TRONIER B. , HEDING L. G.
Published: January 2008

ABSTRACT. Plasma concentrations of proinsulin and C‐peptide were measured in five children presenting with svere hypoglycaemia associated with elevated plasma levels of immunoreactive insulin (IRI) in order to determine whether the profile of circulating B‐cell products related to the underlying pathophysiology of the pancreas. Results were compared with data from 13 normal infants. Four children, three neonates and a nine year old girl, were subjected to partial or total pancreatectomy. The neonates had nesidioblastosis, nesidioblastosis with a microadenoma, and a functional abnormality without histological derangement respectively; the older child had a localised adenoma. The remaining child, a neonate, had transient hypoglycaemia and elevated IRI levels associated with hyperlactataemia and hyperalaninae‐mia. All the children had markedly elevated plasma proinsulin concentrations; the highest levels were seen in the child with an isolated adenoma and in the neonate with nesidioblastosis and a microadenoma. Both of these children also had substantially elevated plasma C‐peptide concentrations. The remaining three neonates had plasma C‐peptide levels, which although in the normal range for normoglycaemia were inappropriately elevated during hypoglycaemia. It is concluded that elevated proinsulin and C‐peptide concentrations are seen in children with hypoglycaemia associated with increased plasma IRI levels and that the profile of the concentrations does not provide a reliable marker for the nature of the underlying pancreatic abnormality.
Hypothalamo‐Hypophyseal‐Testicular Function in Prepubertal Boys with Acute Lymphoblastic Leukemia following Chemotherapy and Testicular Radiotherapy
Authors: CARRASCOSA A. , AUDI L. , ORTEGA J. J. , JAVIER G. , TORAN N.
Published: January 2008

ABSTRACT. Hypothalamo‐hypophyseal‐testicular function was studied in twenty‐eight prepubertal boys with ALL in clinical and haematological remission. Eighteen were treated with combined systemic chemotherapy (24–36 months) and the other ten, who had testicular leukemic infiltrates, received chemotherapy (38–60 months) and testicular radiotherapy (2000 rad). Plasma levels of LH and FSH were measured before and after stimulation with LHRH (100 μg i.v.) and plasma levels of testosterone before and after stimulation with hCG (1500 IU/48 h/7 doses). In patients treated with chemotherapy alone, mean basal LH and FSH, mean responses to LHRH stimulation and mean testosterone levels after stimulation with hCG did not significantly differ from those of the controls. Five of these patients who had normal testosterone values after three doses of hCG had testosterone values below the normal range after seven doses. In patients treated with chemotherapy and testicular radiotherapy, mean basal FSH and mean responses to LHRH stimulation were significantly higher than those of the controls. Testosterone values after stimulation with hCG were low in three and very low in the other seven. In both groups of patients data from testicular biopsies were consistent with functional results. We conclude that chemotherapy causes slight testicular damage, but chemotherapy and testicular radiotherapy produce severe testicular damage in patients with testicular leukemic infiltrates.
The Angelman or “Happy Puppet” Syndrome: Clinical and Electroencephalographs Features and Cerebral Blood Flow
Authors: BJERRE INGRID , FAGHER BIRGER , RYDING ERIK , ROSEN INGMAR
Published: January 2008

ABSTRACT. Two cases of happy puppet or Angelman syndrome are presented. They have the typical clinical features and represent the first Swedish cases. One of the patients is a man of 75 years of age, which shows that this form of severe mental retardation is well compatible with long life. Extended EEG monitoring may identify the typical EEG abnormality when this is difficult to demonstrate in routine EEG records. The typical laughter has no specific correlate in the EEG and thus is probably not an epileptic manifestation. Regional cerebral blood flow studies were normal in the young patient (11 years of age) but in the older patient showed a reduced cerebral circulation, compatible with organic dementia
A Case of Beckwith‐Wiedemann Syndrome with Conductive Hearing Loss
Authors: DAUGBJERG P. , EVERBERG G.
Published: January 2008

ABSTRACT. A case of Beckwith‐Wiedemann syndrome with conductive hearing loss due to fixation of the stapes is described. This is the second case described in the literature. However, some patients may not have been diagnosed. We suggest that hearing of patients with BWS should be tested at intervals from early childhood.
Cerebral blood flow and left ventricular output in spontaneously breathing, newborn preterm infants treated with caffeine or aminophylline
Authors: Lundstrøm KE , Larsen PB , Brendstrup L , Skov L , Greisen G
Published: January 2008

Aminophylline and caffeine are commonly used for prophylaxis of apnea in premature infants. Previous studies have indicated different effects of the drugs on cerebral circulation. Therefore, we have compared the acute effects of bolus administration of caffeine citrate or aminophylline on left ventricular output, heart rate, blood pressure and global cerebral blood flow. The study group consisted of 33 newborn, spontaneously breathing, preterm infants randomly assigned to receive either aminophylline 5mg/kg (n= 19) or caffeine citrate 20mg/kg (n= 14). Two hours after iv drug administration, global cerebral blood flow measured by the Xe‐clearance technique was significantly lower after aminophylline than after caffeine (mean(SD)): 13.2 (+2.9/ ‐ 2.3) versus 17.2 (+7.1/ ‐ 5.1) ml/100 g/min) (p= 0.01). There were no other statistically significant differences in circulatory or ventilatory parameters between the groups. Further studies are needed to clarify the clinical relevance of these results.
Does a family history of atopy influence lung function at follow‐up of infants born prematurely?
Authors: Giffin F , Greenough A , Yuksel B
Published: January 2008

The aim of this study was to assess whether a family history of atopy influenced lung function at follow‐up of infants born prematurely. Analysis was made of thoracic gas volume and airways resistance measurements performed at 1 year of age in 86 infants born at a median gestational age of 29 weeks. These measurements had been made during a prospective follow‐up study. The 30 infants with a family history of atopy were found to have a higher airways resistance (median 35 cmH2O/l/s) than the 56 infants without such a family history (median 30cmH2O/l/s) (p < 0.05). However, when the results from 18 infants with a family history of atopy were compared with 18 controls who were matched for requirement for neonatal ventilation, parental smoking and were within at least 1 week of gestational age, no significant difference in airways resistance was found between the two groups. Multiple regression analysis demonstrated that gestational age and birth weight explained the apparent relationship between a family history of atopy and an elevated airways resistance at follow‐up.
Thyroid gland volume as measured by ultrasonography in preterm infants
Authors: Ares S , Pastor I , Quero J , Morreale de Escobarh G
Published: January 2008

The volume of the thyroid gland was determined by ultrasonography in 30 preterm infants (27‐36 weeks' gestation) born in Madrid. Thyroid gland volume significantly increased (p < 0.01) with postnatal and postmenstrual age and was very well correlated with body weight, height and surface area (p < 0.01). Serum thyroid hormones 3,5,3'‐triiodothyronine (T3) and free thyroxine (FT4) were linearly correlated with postnatal and postmenstrual age, thus T3 and FT4 levels were also correlated with thyroid gland volume (p < 0.05). We report measurements of the thyroid gland volume obtained by ultrasonography in this group of preterm infants. Quantitative determination of thyroid gland volume is more accurate for the diagnosis of goitre than clinical criteria. It is also interesting to determine the thyroid gland volume in the neonatal period when the thyroid is particularly hypersensitive to the effects of iodine deficiency and excess.
Prediction of acute otitis media with symptoms and signs
Authors: Uhari M , Niemelä M , Hietala J
Published: January 2008

We carried out a prospective study to analyse if it would be possible to predict the coexistence of acute otitis media on the basis of symptoms and signs of infection. Of the 658 patients admitted to hospital during the period concerned, 197 (29.9%) had otitis media. For each child with otitis, the next patient of the same age was chosen as a control. The risk of having otitis media was increased among patients with cough, rhinitis and earache. All three variables together correctly classified 67% of those not having otitis media and 63% of those with acute otitis, compared with the 50% which would theoretically be achieved by chance alone. Prediction was worst (55%) among patients younger than 2 years of age not having otitis media and best among older patients who had otitis media, i.e. 78%. Prediction on these grounds would have caused significant over‐treatment, and one‐third of the otitis cases among the youngest group would have been missed. Thus it is important to always examine the ears of a child with an infection in order to reliably exclude the possibility of acute otitis media.
Reduced carnitine and antiepileptic drugs: cause relationship or co‐existence?
Authors: Zelnik N , Fridkis I , Gruener N
Published: January 2008

Serum carnitine was measured longitudinally before and after therapy in 15 patients receiving valproic acid, 14 patients receiving carbamazepine and 8 patients receiving phenobarbital. The patients who received valproic acid showed a significant reduction in free (and total) serum carnitine (mean (SE) 37.6 (6.2)/umol/l without valproic acid, 29.1 (1.6)/xmol/l with valproic acid (p < 0.001)). Such an effect was not found in patients receiving carbamazepine or phenobarbital.
Head trauma among children in Reykjavík
Authors: Arnarson EÖ , Halldórsson JG
Published: January 2008

The incidence of head trauma (ICD9 850‐854) among children in the Reykjavík area, aged 0‐14 years, was studied over a 5‐year period, 1987‐1991, using hospital records. On average, 72 children with head trauma were admitted to hospital each year, indicating an annual incidence of 1.70 per 1000 population. Fourteen percent of children admitted to hospital with head trauma suffered the more severe forms of brain injury (ICD9 851‐854) (annual incidence of 0.28 per 1000). Seven children died from brain injury, indicating an annual death rate of 0.03 per 1000. Falls were the most common cause of head trauma (62%), followed by traffic accidents (19%). On average, one to two severely brain‐injured children received rehabilitation each year.
Profile of urinary bile acids in familial intrahepatic cholestasis with Coombs’negative haemolytic anaemia
Authors: Kimura A , Ushijima K , Suzuki M , Tohma M , Inokuchi T , Kato H
Published: January 2008

We present two male siblings with intrahepatic cholestasis and prolonged indirect hyperbilirubinaemia. Their familial intrahepatic cholestasis syndrome was characterized by Coombs’negative haemolytic anaemia, without giant cell transformation of hepatocytes and high concentrations of serum γ‐glutamyl transpeptidase and cholesterol. By gas chromatography‐mass spectrometry, we detected large amounts of 1β‐hydroxylated bile acids, especially lβ,3α,7α,12α‐tetrahydroxy‐5β‐cholan‐24‐oic acid (25.5‐67.9% of total urine bile acids) in the urine during phenobarbital therapy. However, the amount of urinary 1β‐hydroxylated bile acids gradually decreased as the disease progressed. At the end‐stage, we detected large amounts of 7α,12α‐dihydroxy‐3‐oxochol‐4‐en‐24‐oic acid (19.6% of total urine bile acids). The ratio of 7α,12α‐dihydroxy‐3‐oxochol‐4‐en‐24‐oic acid to cholic acid in the urine was 0.8. We conclude that in infants with end‐stage liver failure, the microsomal hydroxylation of bile acids is impaired and the excretion of Δ4‐3‐oxo bile acids is increased.Familial intrahepatic cholestasis, Coombs’negative haemolytic anaemia, 1β‐hydroxylated bile acids, unsaturated ketonic bile acids
Response to oral β‐carotene supplementation in patients with cystic fibrosis: a 16‐month follow‐up study
Authors: Winklhofer‐Roob BM , Van't Hof MA , Shmerling DH
Published: January 2008

The aim of this study was to determine the efficacy of long‐term oral β‐carotene supplementation for correcting impaired β‐carotene status in cystic fibrosis patients. Thirty‐five patients (2.3‐30.5 years of age) with coefficients of fat absorption of 46‐96% (median 88%) received β‐carotene 0.5 mg/kg daily and were followed over a 16‐month treatment period. Baseline plasma β‐carotene concentrations in patients (meanSD, 0.090.06 μmol/1) were significantly lower than those of age‐matched controls (0.860.56 μmol/1) (p < 0.0001). Concentrations increased rapidly and reached a plateau at or before 3 weeks that was maintained throughout the study period. Values obtained at 3 weeks (0.890.64 μmol/1) were significantly higher (p < 0.0001) than those at baseline and did not differ from controls. Plasma retinol and α‐tocopherol concentrations increased during the observation period, but remained within normal ranges. Plasma retinyl palmitate, which was below the detection limit in all but one patient at baseline, did not increase. Thus oral β‐carotene supplementation is effective and normalizes β‐carotene status of cystic fibrosis patients without evidence of significant side effects.β‐Carotene, cystic fibrosis, LDL‐cholesterol, oral supplementation, retinol, α‐tocopherol