bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes of mineral metabolism in juvenile chronic arthritis
Authors: Tzoufi M , Siamopoulou‐Mavridou A , Challa A , Lapatsanis PD
Published: January 2008

Thirty five children with ambulant JCA were studied to assess the biochemical parameters of bone metabolism. The mean age of the study group was 8.8±4.1 years and the mean duration of active disease 3.8±1.3 years. According to the onset of the disease the children belonged to the systemic (7), polyarticular (12) and pauciarticular type (16). All the patients were treated with NSAIDs. In addition the polyarticular group received either gold injections or D‐penicillamine and the systemic group, steroids for at least 3 months. Two groups of controls were studied. The first one included fifteen children without chronic arthritis or bone disease and the second, four children who were treated with corticosteroids for a variety of reasons. In the group with systemic JCA Se Pi (1.28±0.29 mmol/l) and renal phosphate reabsorption (TmP/GFR=1.07±0.18) were significantly lower than in the control groups (1.50±0.19; 1.54±0.25 mmol/l, p<0.01 and 1.35±0.18; 1.29+0.23 mmol/l GF, p<0.05). Also lower were serum alkaline phosphatase (58±16.4 versus 83±24.2 and 80±15.6 IU/l, p<0.05), osteocalcin (5.5±4.7 versus 11.0±4.5 and 10.0±5.7 ng/ml, p<0.05), 25OHD (15.6±4.9 versus 27.3±6.2 and20.6±9.8 ng/ml, p<0.001) and l,25(OH)2D (12.1±6.0 versus 20.9±11.0 and 27.6±3.2 pg/ml, p<0.05). In the other two groups of patients (polyarticular and pauciarticular) all the values were found to be in the normal range except for the concentration of 25OHD which was significantly lower (17.8±4.7 ng/ml, p<0.001) in the active group than in the patients in remission (27.0±7.1 ng/ml). Hypercalciuria (UCa/UCr>0.18 mg/mg and Ca excretion >4 mg/Kg/24h) was observed in 18% of JCA patients. In conclusion the children with systemic onset JCA seem to have a disturbance in bone and mineral metabolism. The activity of JCA appears to lead to lower levels of 250HD.
A paediatric Crohn's disease activity index (PCDAI). Is it useful?
Authors: Harms Hinrich Karsten , Blomer Roland , Bertele‐Harms Rose‐Marie , Shmerling David H , König Michael , Spaeth Annerose ,   The Study Group on Crohn's Disease in Children and Adolescents
Published: January 2008

Since 1976, various activity indices for Crohn's disease have been developed but none has been suitable for use in the paediatric age group. Therefore, the German‐Swiss Study Group on Crohn's Disease in Children and Adolescents decided to develop their own paediatric Crohn's disease activity index (PCDAI) by multiple regression analysis of prospectively collected data. The result was a simple index consisting of two clinical (appetite, number of stools/week) and four laboratory variables (erythrocyte sedimentation rate, serum iron and α2‐globulin concentrations and bands as percentage of white blood cells). Applying the index to patients who were followed‐up, it could be demonstrated that the changes in PCDAI inversely reflected the changes in weight and that the surgical removal of the inflamed parts of the gut reduced the disease activity index to levels comparable to those obtained in patients after successful, exclusively conservative, treatment. Low disease activity was maintained for at least three years.
Polyunsaturated fatty acids in infant nutrition
Authors: Decsi Tamas , Koletzko Berthold
Published: January 2008

The availability of long‐chain polyunsaturated fatty acids (LCP), such as arachidonic (C20:4n‐6) and docosahexaenoic (C22:6n‐3) acids, is important for early human growth and development. The capacity for endogenous synthesis of LCP from the precursor fatty acids lineoleic (C18:2n‐6) and alpha‐linolenic (C18:3n‐3) acid is limited in preterm and probably also in term infants. In utero, LCPs seem to be transferred preferentially from the mother to the foetus by the placenta. After birth, breastfed infants receive preformed dietary LCP with human milk. In contrast, most current infant formulae are devoid of LCP. Premature infants fed such formulae develop rapid LCP depletion of plasma and tissue lipids, which is associated with reduced visual acuity during the first postnatal months. Therefore, LCP enrichment of formulae for premature infants is desirable. Recent observations indicate that term infants fed conventional formulae also exhibit lower plasma LCP values and may show functional disadvantages, but these data require further confirmation prior to drawing definite conclusions.
Epidemiology of necrotizing enterocolitis
Authors: Kosloske AM
Published: January 2008

Necrotizing enterocolitis (NEC) is a worldwide problem that has emerged in the past 25 years as the most common gastrointestinal emergency in neonatal intensive care units (NICU). In the United States the incidence ranges from 1 to 7.7% of NICU admissions. Ninety percent of the patients are premature infants. Mucosal injury, bacterial colonization and formula feeding are the three major pathogenetic factors that have been documented in most infants who have developed NEC. However, NEC may develop only if a threshold of injury, imposed by the coincidence of at least two of three events (intestinal ischemia, pathogenic bacteria, and excess of protein substrate) is exceeded. Immunological immaturity of the gut in premature babies may represent the crucial risk factor.
Platelet‐activating factor, tumor necrosis factor, hypoxia and necrotizing enterocolitis
Authors: Hsueh W , Caplan MS , Sun X , Tan X , MacKendrick W , Gonzalez‐Crussi F
Published: January 2008

The pathogenesis of necrotizing enterocolitis (NEC) is poorly understood. We have established several animal models of NEC by using a combination of various stimuli and stress, including endotoxin, PAF, TNF, and hypoxia. We discuss the mechanism of their actions and the possible roles of these factors in the pathogenesis of human NEC.
Plasma cytokine levels in necrotizing enterocolitis
Authors: Morecroft JA , Spitz L , Hamilton PA , Holmes SJK
Published: January 2008

Plasma concentrations of tumour necrosis factor (TNF) and interleukin‐6 (IL‐6) were measured by ELISA in samples taken from 24 infants with necrotizing enterocolitis (NEC) between 0 and 306 h from diagnosis. TNF was detected (>10pg/ml) in 71% samples with a mean of 48pg/ml (95% CI 42 to 55 pg/ml) and did not vary with either time from diagnosis or severity of disease. IL‐6 was raised during the first 48 h with a significant difference between stage II (mean 127 pg/ml, 95% CI 10 to 329 pg/ml) and stage HI (mean 3127 pg/ml, 95% CI 1809 to 4445 pg/ml, p= 0.001). Postoperative plasma IL‐6 concentration fell to similar levels seen in stage II (mean 150 pg/ml, 95% CI 37 to 283 pg/ ml, p= 0.79). We conclude that plasma concentration of IL‐6 rather than TNF reflects the clinical severity of necrotizing enterocolitis and that the relative level of these cytokines has important implications for the use of anti‐cytokine therapy in NEC.
Is the elimination of endotoxin and cytokines with continuous lavage an alternative procedure in necrotizing enterocolitis?
Authors: Birk D , Berger D , Limmer J , Beger HG
Published: January 2008

Ascites fluid was obtained intraoperatively in 12 consecutively treated neonates (6M, 6F, mean weight 940 g, mean gestational age 27th week, lethality 3/12) suffering from necrotizing enterocolitis (NEC). The concentrations of endotoxin and cytokines (IL‐1, IL‐6, TNF) were determined. Endotoxin and interleukins were excessively elevated in all patients, TNF only in those who survived. Postoperative treatment included the use of a continuous abdominal lavage system. This therapeutical procedure allows the elimination of endotoxin and cytokines out of the abdominal cavity in order to reduce their adverse biological effect.
Surgical treatment of necrotizing enterocolitis: when? how?
Authors: Parigi GB , Bragheri R , Minniti S , Verga G
Published: January 2008

In 10 years (1981–1990) 28 out of 54 neonates (51.8%) with definite necrotizing enterocolitis (NEC) underwent surgery. Operation was performed at 13.5 ± 8.8 (range 3–38) days of life, after 1.7 ± 1.5 (range 1–6) days from the onset of symptoms. Aiming to perform laparotomy before the occurrence of perforation, surgery was liberally indicated in stage Ilia, according to Walsh‐Kliegman. Explorative laparotomy (+peritoneal drainage in 2 cases) was performed in 4 patients with massive intestinal necrosis: all died within 3 days of surgery. In one neonate, only pneumatosis was present and resection was not considered mandatory. Intestinal resection and enterostomy was performed in 17 neonates, 5 of them with perforation; three developed an intestinal stenosis. Enterostomy was closed after 116.2 ± 61.8 days (range 26–193); 11 patients (64.7%) are long‐term survivors. Intestinal resection and primary anastomosis was performed in 6 babies, 3 of them with perforation. Postoperatively, 2 dehiscences and 1 stenosis were recorded, but all children survived. In our opinion, resection followed by primary anastomosis seems to be the most satisfactory surgical option.
Maternal behaviors: evidence that they feed back to alter brain morphology and function
Authors: Modney BK , Hatton GI
Published: January 2008

We review evidence suggesting that the brain of maternally behaving rats is altered as a result of the behavior of the animal towards her pups. Morphological changes seen in the supraoptic nucleus, which contains oxytocinergic neurons important for lactation, are observed not only in parturient, lactating animals but also in virgin animals induced by the presence of rat pups to behave maternally. The supraoptic nuclei of lactating and maternally behaving virgin animals have a higher incidence of dendritic bundling relative to non‐maternal virgin animals. Also, stimulation of the lateral olfactory tract in in vitro brain slices elevates electrotonic coupling among supraoptic neurons only in maternally behaving animals and not in male or non‐maternal virgins. In general the evidence presented supports the idea that maternal behavior in lactating and non‐lactating animals, can have profound effects on the morphology and physiological functioning of oxytocinergic neurons in the hypothalamus.
The role of lactogenic hormones in maternal behavior in female rats
Authors: Bridges Robert S
Published: January 2008

Most mammals display an immediate onset of maternal care towards their offspring at parturition. In contrast, inexperienced, nulliparous females are often slow responders and show less intensity in their maternal responses. The transition from a slow responder in non‐parous females to a rapid response at parturition is facilitated by the endocrine state of pregnancy. The present report reviews recent evidence from my laboratory demonstrating a role for prolactin in the stimulation of maternal behavior in the rat and presents new findings suggesting that the conceptus, through its secretion of placental lactogens, helps prime the maternal brain (one site being the medial preoptic area) to respond maternally at parturition.
Learning as adaptation of the infant
Authors: Alberts Jeffrey R
Published: January 2008

The present report advocates an adaptive, ecological approach to the study of learning in infants. Concepts of developmental niche and ontogenetic adaptation are applied to early mammalian development. Within this conceptual framework, it is asserted that learning cannot be fully understood separately from a behaving body; that learning is a dimension of behavior and physiology. The role of learning in the development of ingestive behavior, especially suckling and the transition to solid food, is used to illustrate the potential of studying learning in development. These considerations are offered as examples of an alternative approach to the empirical study of learning by infants. The approach advocated herein can be applied to clinical issues: developmental adaptations evolved in contexts that differ from our modern environments. Exposure to contexts or contingencies that are evolutionarily unexpected may inadvertently create pathology.
Effects of growth hormone therapy in prepubertal children with short stature secondary to intrauterine growth retardation
Authors: Chaussain JL , Colle M , Landier F
Published: January 2008

A total of 130 short children were included in a French multicentre study and randomized between a control group (group A) and two groups treated with daily subcutaneous injections of GH at doses of 0.7 IU/kg/week (group B) and 1.4 IU/kg/week (group C) for 2 years. Height velocity was significantly increased (p<0.0005) in groups B and C, with a greater increase in group C than in group B (p< 0.001). The benefit after 2 years compared with controls was 4.3 cm in group B and 5.9 cm in group C. The rate of bone maturation was not affected by GH therapy. These results led to the conclusion that 2 years of treatment with GH improves final height prognosis in children with short stature secondary to IUGR, and that this effect is dose dependent. The effect on final height has still to be demonstrated.
Epidemiological and serological studies in HIV‐infected Ethiopian immigrants to Israel
Authors: Pollack S , Ben‐Porath E , Fuad B , Raz R , Etzioni A
Published: January 2008

In the last 10 years, Ethiopian Jews have immigrated to Israel in large numbers. Up to 1990 they came directly from their remote villages in northern Ethiopia and no HIV infection was detected in the several thousands that came. In contrast, 1.74% of approximately 14000 new immigrant Ethiopians who arrived in 1991–92, after spending more than a year in Addis Ababa, were HIV positive. Several infants born in Israel following the latter immigration were found to be infected, whereas more than 2500 children born in Ethiopia were negative. Sexual transmission during their stay in Addis Ababa is thought to be the only route of infection, and therefore this is a newly infected population. Immunological studies revealed very low CD4 count in HIV‐infected people. HIV‐negative Ethiopian immigrants to Israel also have a lower CD4 count than the general Israeli population. Further studies are currently under way to look at the natural history of this particular HIV‐infected group.
Prevention program of HIV infection in Ethiopian new immigrants to Israel
Authors: Etzioni A , Pollack S , Ben‐Ishai Z
Published: January 2008

In 1991, more than 15,000 Ethiopian Jews immigrated to Israel after spending more than a year in Addis Ababa. They came from remote villages and had had no contact with modern medicine for centuries. About 2% of these new immigrants were found to be HIV positive. Their completely different background forced the Israeli government to develop a special educational program explaining about the modes of HIV infection and prevention measures. The staff participating in the program were mainly Ethiopian Jews who immigrated to Israel before 1990 and were employed as nurses or social workers. The goal of the study was to prevent the spread of the virus; thus the target population was those who were infected with HIV. As most of them were illiterate, posters with pictures were used to explain risk factors, and lectures were given explaining what a virus is and, especially, the “carrier state”. Using this program the spread of HIV inside the Ethiopian community seems to have diminished.
Evolution of immunological abnormalities in HIV infection by vertical transmission
Authors: Español T , Caragol I , Bertran JM
Published: January 2008

Forty‐four children infected through vertical transmission, from a total of 146 born to HIV‐positive mothers, were studied. Immunological data were analysed and compared with those of the non‐infected children. Two transmission patterns emerge from the clinical and immunological characteristics: (i) infants infected during pregnancy with severe immunodeficiency and clinical manifestations before the age of 1 year, and (ii) children probably infected perinatally, who have better clinical outcome. Immunological data are important for prognosis and early therapeutic protocols to be established.
Vertical transmission of HIV infection
Authors: Newell Marie‐Louise , Peckham Catherine
Published: January 2008

Transmission of HIV infection from mother to child may occur before, during or after delivery. Estimates of the rate of vertical transmission range from 15–20% in Europe to 25–35% in Africa. Mother‐to‐child transmission is associated with progression of disease in the mother, severe prematurity and breastfeeding. The association with mode of delivery needs further investigation. Attention is now being given to intervention to reduce mother‐to‐child transmission of HIV infection.
Antiretroviral therapy for children
Authors: Krasinski Keith
Published: January 2008

Advances in the development of antiviral drugs have been rapid and dramatic. Since the recognition of HIV‐1 as the cause of AIDS in 1984, and improved understanding of retroviral replication and pathogenesis, three antiviral drugs, Zidovudine, Didanosine, and Zalcitabine, have been developed to the point of routine use in humans. There is substantial experience with the former two in children. Despite being unable to cure HIV‐1 infection, the benefits of antiretroviral therapy, including extended survival and reductions in opportunistic infections in adults, and improved weight gain and well‐being in children, are strong arguments for routine treatment of symptomatic disease. Because these agents may also interfere with human cellular processes and have toxicities including anemia, neutropenia, pancreatitis, and neuropathy, their routine use for the treatment of asymptomatic children requires further controlled study. There are multiple candidate agents being developed for entry into clinical trials. An additional potentially effective strategy is the use of combinations of drugs at the same time or in sequence to maximize the viral targets being attacked, while minimizing toxicity, and to prevent the emergence of a drug‐resistant virus.
The use of antibiotics in the treatment and prevention of infection in HIV‐infected children
Authors: Ruga E , Giaquinto C , Cozzani S , Giacomelli A , Pagliaro A , Mazza A , De Manzini A , Laverda AM , D'Elia R
Published: January 2008

Children with HIV infection have an unusual susceptibility to bacterial infection, related to several immune abnormalities. Selection of initial antibiotic therapy must be individualized in these children. Patients with community‐acquired disease are most likely to have infection by polysaccharide‐encapsulated bacterial organism, most commonly Streptococcus pneumoniae and less frequently by Haemophilus influenzae type b. If it is possible to treat the patients at home, the use of amoxicillin‐clavulanic acid might be appropriate. Other authors propose management with parenteral ceftriaxone because of the better compliance and the malabsorption. In hospitalized patients, concern for Gram‐negative enteric pathogens other than polysaccharide‐encapsulated organisms requires initial therapy with a third‐generation cephalosporine in combination with an aminoglycoside. Trimethoprim‐sulfamethizole is the most common drug used in HIV‐infected children because it is recommended for the initial therapy and for prophylaxis of Pneumocystis carinii pneumonia, which occurs in as many as 42% of these children.
HIV vaccine development and clinical trials
Authors: Hoff Rodney , McNamara James , Fowler MaryGlenn , McCauley Marybeth
Published: January 2008

The magnitude of HIV pandemic has made the development of HIV vaccines an urgent biomedical research priority. Although the biologic problems in designing a vaccine for a chronic viral infection like HIV are formidable, there has been encouraging progress. More than a dozen first generation prophylactic HIV vaccine candidates have completed phase I human trials that have established the safety and immunogenicity of these products in adults. A phase II trial of two HIV subunit envelope vaccines in adults at high risk of HIV infection is underway in the United States, and preparations for phase III efficacy trials have begun. Preliminary studies are under way to evaluate the potential application of active and passive immunization for preventing vertical transmission of HIV. Because of the higher rate of HIV transmission and a more abbreviated time course to disease, it may be more efficient to evaluate the efficacy of HIV vaccines in HIV infected pregnant women and their offspring than in adults who are exposed sexually to HIV.
Paediatric AIDS: A new child abuse
Authors: Oletto S , Giaquinto C , Seefried M , Ruga E , Cozzani S , Mazza A , De Manzini A , D'Elia R , Zacchello F
Published: January 2008

In relation to youth rights, a new view has been created in recent decades that is included in the fundamental law of the child: the recognition of the right to education and the chance to develop a mature personality capable of creativity and liberty. Because of HIV infection it is very important to pay particular attention to the rights of the seropositive child and children born to seropositive mothers, which may be hampered not only in developing countries but also in the industrial world. HIV‐affected children and their families are becoming abused and at high risk of becoming abused and this encroaches upon youth rights. As a consequence, in 1991 the Italian Society of Paediatrics issued a “Charter for the rights of seropositive children”, which became an important document for all health care and social workers who deal with HIV‐affected children. In this paper, we also consider the impact of HIV infection on the three main rights of children: the right to live, the rights of security and the rights of socialization.
Maternal and pediatric AIDS in the United States: the current situation and future research directions
Authors: Blank Anne , Mofenson Lynne M , Willoughby Anne , Yaffe Sumner J
Published: January 2008

The epidemic of HIV infection and disease in women, adolescents and children represents a complexly intertwined biological and social challenge to health care workers and researchers alike. When considering various issues in confronting this epidemic, women must be viewed as individuals important in their own right, as the primary caretaker of their family members (both infected and uninfected), and as the sexual partners of men who may or may not be infected. Of the myriad of compelling biological questions facing AIDS researchers today, two of the most interesting involve the timing and determinants of vertical transmission and the natural history of HIV infection and disease in women. Scientifically, confronting this epidemic involves research into pathogenesis, epidemiology, natural history, treatment, and prevention of HIV infection. Primary emphasis in the research arena in HIV/AIDS in the United States is focused on therapeutic and prophylactic research. Other research issues are very important, including studies of early diagnostic techniques, behavioral research concerning reproductive choices, the role of breastfeeding in HIV transmission, HIV‐specific adolescent issues, and surrogate markers of disease progression.
Pitfalls in the design and manufacture of infant formulae
Authors: Sawatzki G , Georgi G , Kohn G
Published: January 2008

The composition of modern infant formulae is basically oriented on the “golden standard” human milk and influenced by several official regulations and recommendations (EC, ESPGAN, etc.). This article will focus on two recent improvements in the field of long‐chain polyunsaturated fatty acids (LCPs) and protein hydrolysates. The addition of LCPs for preterm formulae was recommended recently by ESPGAN (the European Society for Pediatric Gastroenterology and Nutrition). Our research has focused on this problem for many years and we have found a good source of LCPs using specially prepared egg‐yolk lipids. Others have used fish oils and run into the problem of growth retardation. Therefore, the possible sources of LCPs have to be discussed very critically and the alternatives will be shown. Also, new developments like the use of single‐cell oils will be discussed. Second, the use of protein hydrolysates have been introduced for the so‐called hypoantigenic or hypoallergenic formulae. Hypoantigenic formulae for preventive use have to be differentiated clearly from hypoallergenic formulae for treatment of proved cows’milk protein allergy. The problems of designing suitable hydrolysates that are low in antigenicity and good in taste will be outlined. The determination of the molecular weight distribution by gel chromatography will be compared critically with the newer techniques. The ELISA technique for testing the antigenicity is recommended before any in vivo evaluation. So far, the anaphylactic guinea‐pig model is the most sensitive in vivo testing method. Summing up, modern infant formulae manufacture is much more dependent on modern laboratory techniques, which have to be chosen critically and must be adapted to the newest state of the art.
Diet and the essential fatty acid status of term infants
Authors: Kohn G , Sawatzki G , van Biervliet JP , Rosseneu M
Published: January 2008

Long‐chain polyunsaturated fatty acids with 20 and 22 carbon atoms (LCPs) seem to play an important role during the rapid development of the infant brain in the late fetal and early postnatal period. These LCPs are integral constituents of biological membranes and they are involved in the regulation of functional properties like fluidity, permeability and activity of membrane‐bound enzymes. Human milk contains LCPs in an amount of 0.5–3 wt% of total fatty acids, whereas commercially available infant formulae are almost free of them. Recently, several clinical trials, primarily with preterm infants, have reported that the content of LCPs in the blood and a functional parameter like visual acuity correlate with the content of LCPs in the diet. In this clinical trial we studied the effect of different diets on the fatty acid pattern of plasma and erythrocyte lipids of healthy term infants during the first 3 months of life. Breast‐fed infants were compared with formula‐fed babies who received a commercially available formula without LCPs or a new experimental formula enriched with LCPs that was similar to human milk. The results indicate that the introduction of milk feeding leads to marked differences in the blood lipid composition during the first months of life, independent of the feeding regimen. Secondly, the supplementation of a formula with LCPs seems to result in a blood lipid composition similar to infants fed with human milk. This supports the hypothesis that the newborn term infant has a limited desaturating capacity and depends on an exogenous supply of LCPs during the first months of life.
Children of alcoholics. Predictors for psychopathology and addiction
Authors: Gunning WB , Pattiselanno SE , van der Stelt O , Wiers RW
Published: January 2008

Children of alcoholics have a higher risk of psychopathology and alcoholism. Therefore, in 1993 the Amsterdam Institute for Addiction Research initiated a study on vulnerability markers and risk factors in children of alcoholics, aimed at identifying predictors for the development of psychopathology and addiction in children of alcoholics. This article provides a summary of the background, rationales and aims of the study. With more specific and sensitive biological vulnerability markers that indicate risk status, more effective preventive interventions might become available. The biochemical part of the study aims at answering the question whether adenylate cyclase is a vulnerability marker for alcoholism. The psychophysiological part is directed at event‐related potentials during task performance to clarify the nature of the brain and cognitive functions that may underlie or relate to vulnerability to alcoholism. The third part, the psychological component, aims at possible psychological mechanisms of enhanced risk of addition in children of alcoholics as well as the relationship with childhood psychopathology.
Amphetamine addiction during pregnancy: 10‐year follow‐up
Authors: Eriksson M , Zetterström R
Published: January 2008

Sixty‐five children born to women who all used amphetamine during pregnancy have been followed prospectively since birth 1976–77. They have been tested and examined at one, 4 and 8 years of age. In addition, information about the school situation was collected after 10 years. Twenty percent of the children were put in foster homes at birth, and after 10 years 70% were in foster homes. The children showed a normal intellectual capacity. However, at 10 years of age 8 children (12%) attended one class below what was normal for their biological age (normal in Sweden < 5%). At 4 years of age 35% had an aggressive behaviour and at 8 years 23%. There was a statistically significant correlation between aggressive behaviour and amphetamine exposure during fetal life. At both 4 and 8 years of age 40% were considered to have a poor adjustment, which correlated with socio‐environmental factors. Lower values for weight and length also showed a correlation with socio‐environmental factors. The study shows that amphetamine abuse during pregnancy will influence development of exposed children at least up to the age of 10 years.
Substance use in pregnancy: do we care?
Authors: Boer K , Smit BJ , van Huis AM , Hogerzei HV
Published: January 2008

Two cohorts of substance‐using women were compared retrospectively. From 1969 to 1979 a very high perinatal mortality rate (PMR 9.8%) was found among 92 polydrug‐using women (1 twin excluded). Preterm delivery occurred in 25% of all pregnancies and in 30% of the children birth weight was below the 10th percentile. Nineteen women using heroin only had a worse fetal outcome (PMR 32%, preterm delivery in 47%, birth weight < 10th percentile in 42%). These results led to a strict surveillance system. In the period 1980–1989, 240 women (4 twins excluded) delivered after 16 weeks. Total fetal loss decreased to 2.1% and PMR to 0.4%, which was similar to results in controls. However, 22% of the women still delivered before 37 weeks and 27% delivered a child < 10th percentile. Methadone‐using women were able to halve their dosage during pregnancy and 16 were detoxified. Multivariate analysis within the substance users of the second cohort showed that the neonatal abstinence syndrome, but not the (registered) amount of opiates used, was related to a lower birth weight. Not coping with prenatal care was related to a shorter pregnancy length. Multivariate analysis, including the controls, showed a significant relation of birth weight (345 g lower) with substance use. Also, head circumference was 0.8 cm smaller. Length of pregnancy however was related to smoking. This study shows that it is difficult to make substance users attend prenatal care, but also that women coping with prenatal care reduce substance intake. Opiate use might be responsible for lower birth weight, although not in a clear dose–response relationship, whereas lifestyle, as represented by not coping with prenatal care and the quantity of cigarette smoking, shortens the length of pregnancy.
Mineral balance and whole body bone mineral content in very low‐birth‐weight infants
Authors: Lapillonne AA , Glorieux FH , Salle BL , Braillon PM , Chambon M , Rigo J , Putet G , Senterre J
Published: January 2008

Fat and mineral metabolic balance studies were performed in 25 normal very low‐birth‐weight infants ( 1500 g at birth) fed either pooled pasteurized human milk supplemented with calcium, phosphorus and magnesium, or a preterm formula. Calcium, phosphorus and magnesium intake were similar in both groups and averaged 100mg/kg/day, 72 mg/kg/day and 8 mg/kg/day, respectively. Calcium and phosphorus retention was higher in the subjects fed fortified human milk than in those receiving a preterm formula (65±14 and 62±9mg/kg/day versus 55±12 and 47±7mg/kg/day respectively). The difference was only significant for phosphorus. Magnesium retention was similar in the two groups and averaged 3 mg/kg/day. Fat intake and absorption was significantly higher in the preterm formula fed group than in the one fed fortified human milk (5.5±0.4 g/kg/day and 88±4% versus 4.2±1 g/kg/day, 79±6% respectively). Assessment of the whole body bone mineral content by dual energy X‐ray absorptiometry was performed at 3 and 6 months of age in another group of 25 low‐birth‐weight infants fed either fortified human milk or a preterm formula. Whole body bone mineral content (BMCt) was low (43.3±30.8 g of hydroxyapatite) at 3 months of age (theoretical term) compared to normal full‐term newborns at birth. There was no significant influence of the diet. At 6 months of age, BMCt reached 168.6±36.6g, a value similar to that of full‐term newborns, with no significant difference between the two regimen groups. The deficit in the 12 subjects who had a BMCt under 30 g at 3 months of age had been corrected at age 6 months. Premature babies fed a pooled pasteurized human milk enriched with calcium, phosphorus and magnesium favored a better retention of calcium and phosphorus. However, no significant influence of the two diets studied was observed on the gain in BMCt over the first 6 months of life.
Prediction of final height in short, normal and tall children
Authors: Karlberg J , Lawrence C , Albertsson‐Wikland K
Published: January 2008

Measurements of final height were made on more than 4000 children in the final grade of school in Gothenburg in 1992; at the same time, mid‐parental heights were recorded. These data were combined with other information (sex, length of gestation, size at birth, estimated age at peak height velocity (PHV) and height measurements made before 8 years of age) and used in a multiple regression analysis to assess the strength of the linear relationship between attained final height and these other potentially predictive measures of adult height. The R2 value increased from 0.16 at birth to 0.64 when the child was 8 years old. The inclusion of mid‐parental height in the regression analysis contributed significantly to the explained variation in final height, especially at the earlier ages; the further addition of size at birth and age at PHV provides a small increase in the explained variation. The probability that the final height of a child will be below ‐2 or above +2 standard deviation scores (SDS) was assessed, based on previous SDS values for height when younger and on mid‐parental height SDS. As a result of the large sample size included in the analyses, considerable confidence can be placed on the accurate prediction of final height values in the range ‐2.5 to +2.5 SDS.
Psychosocial assessment of children with short stature: a preliminary report
Authors: Skuse D , Gilmour J , Tian CS , Hindmarsh P
Published: January 2008

Previous studies that have examined the psychosocial adjustment of children with short stature have often been flawed, for two main reasons: first, a lack of sample homogeneity and, secondly, the measures of adjustment used have been limited in terms of their sensitivity. This paper examines psychological functioning in the following four broad areas: cognition, social behaviour, emotional adjustment and self‐concept. A sample of children referred to growth clinics (mean height below ‐2 SDS) and a comparison group, recruited from the referred childrens’classes at school, were assessed. Children were prepubertal (age range, 6‐11 years) and had no organic cause for their short stature. Parent, teacher and peer reports were used in the assessment, which included sociometric measures in the classroom. The children with short stature described themselves as equally well supported as the comparison children in terms of social support by parents, teachers, peers and friends. Peers reported the short children to be well accepted within their class. Compared with control children, there was a trend for short children to be described by their peers as socially better adjusted than average. Teacher and parental accounts revealed significant group differences in terms of reported behaviour, with poorer attention and more thought problems among the children with short stature. Further analysis suggested, however, that their slightly lower IQ than children of normal height (95.8 ± 18.7 (mean ± SD) compared with 105 ± 15.4) accounted for a greater proportion of the variance in these findings than short stature per se. There is little evidence to indicate that short prepubertal children are psychosocially maladjusted. Their academic performance was poorer than expected on the basis of their cognitive abilities. Reports of immature and impulsive behaviour may not be applicable to a sample of children not referred to a growth clinic.
Association between haplotypes, Hind III‐VNTR alleles and mutations at the PAH locus in Sicily
Authors: Romano V , Call F , Guldberg P , Güttler F , Indelicato A , Bosco P , Ceratto N
Published: January 2008

In this study we report previously undescribed associations between mutations, haplotypes and a minisatellite polymorphism (Hind III VNTR) of the PAH gene in the Sicilian population. Analysis of the association between mutations and linked polymorphisms between Sicilians and other Mediterranean populations may be a useful tool to study the time‐space origin of mutant PAH genes in Southern Europe.
Ectopic transcription: an application to the analysis of splicing errors in phenylalanine hydroxylase mRNA
Authors: Takahashi K , Masamune A , Kure S , Matsubara Y , Narisawa K
Published: January 2008

Previous studies have identified various mutations in the phenylalanine hydroxylase (PAH) gene responsible for classical phenylketonuria. These mutations can explain 99% of mutant alleles in the Danish population (1). In many other populations phenylketonuria mutations have yet to be identified, especially in Orientals. For example, 40% of mutant alleles in Chinese and Japanese (unpublished data) and 60% in Turkish phenylketonuria patients (2) carry unknown mutations. This is probably due to the racial heterogeneity of the mutations, absence of predominant mutations and the laboriousness of sequencing all 13 exons of the PAH gene. There may be mutations buried deep in introns, which cause aberrant splicing. Analysis of mRNA is one method of overcoming these difficulties. Sequencing cDNA is less laborious than sequencing all exons. cDNA analysis can detect aberrant splicing even if the causative base substitutions cannot be identified around the exon‐intron boundaries.
Mutation analysis of the phenylalanine hydroxylase gene using heteroduplex analysis with synthetic DNA constructs
Authors: Tyfield LA , Stephenson A , Bidwell JL , Wood NAP , Cockburn F , Harvie A , Smith I
Published: January 2008

Using heteroduplex analysis generated with synthetic PCR‐amplifiable DNA we have screened the PKU populations of southwest England and Wales, western Scotland, and southeast and central England for mutations in exons 3, 7 and 12 of the phenylalanine hydroxylase (PAH) gene. The technique characterized three mutations in exon 12, two in exon 3 and five in exon 7. Altogether over 370 PKU chromosomes were screened. In all geographical regions exon 12 mutations (R408W, IVS12ntlg‐ > a and Y414C) accounted for about 40% of mutant chromosomes. Exon 3 mutations (principally I65T) were found on between 9 and 12% of mutant alleles and exon 7 mutations accounted for a further 5‐7%. Heteroduplex analysis is rapid, simple and safe and three constructs covering three exons can identify between 55 and 60% of mutations in various PKU populations of the UK.
A new amino acid mixture permits new approaches to the treatment of phenylketonuria
Authors: Buist NRM , Prince AP , Huntington KL , Tuerck JM , Waggoner DD
Published: January 2008

A new amino acid mixture for incorporation into medical foods for the treatment of hyperphenylalaninemia has been tested in a regular clinic. The mix is designed to be as unobtrusive as possible, consistent with good nutrition. After more than 1 year of trial as a beverage, we have shown that it is safe and well tolerated but that plasma phenylalanine is no better controlled than with some other products. The mix can be incorporated into a large number of different foods without affecting the taste. Occult monitoring of the quantity of medical foods purchased compared with the amounts reported to be consumed in diet histories provides an excellent way to monitor dietary compliance.
White matter abnormalities in phenylketonuria: results of magnetic resonance measurements
Authors: Ullrich K , Möller H , Weglage J , Schuierer G , Bick U , Ludolph A , Hahn‐Ullrich H , Fünders B , Koch H‐G
Published: January 2008

In adolescents and adults with PKU, blood phenylalanine levels above 10mg/dl are generally associated with white matter changes in MRI. The grade of these changes is correlated to most recent blood phenylalanine levels. Based on studies using T2 relaxometry the MRI changes seem to be the consequence of a reversible dysmyelination. The clinical relevance of these white matter changes remains unclear as the extent of MRI alterations did not correlate with IQ, neurological and electrophysiological deficits of the patients. The intracerebral phenylalanine concentration as measured by protonspectroscopy amounts to about 50% of blood phenylalanine concentrations. Preliminary data indicate that brain phenylalanine levels remain constant if blood concentrations exceed 20 mg/dl. This might be of clinical relevance for the treatment of adolescent and adult PKU patients.
Gene therapy for phenylketonuria
Authors: Eisensmith RC , Woo SLC
Published: January 2008

Classical phenylketonuria (PKU) is an autosomal recessive disorder caused by a deficiency of hepatic phenylalanine hydroxylase (PAH). Three different vector systems have been developed to examine the potential of somatic gene therapy for the treatment of PKU. Recombinant retroviral vectors and DNA/protein complexes can efficiently transduce PAH‐deiicient hepatocytes in vitro, but their present phenylketonuria, retrovirus application is limited by their low transduction efficiency in vivo. In contrast, infusion of a recombinant adenoviral vector expressing the human PAH cDNA into the portal circulation of PAH‐deficient mice restores 10‐80% of normal hepatic PAH activity and completely normalizes serum phenylalanine levels. At present, this effect is transient and re‐administration has no further effect. However, this result suggests that PKU can be completely corrected by somatic gene therapy as more persistent vectors are developed.
Responses of Children to Hospitalization
Authors: ZETTERSTRÖM R.
Published: January 2008

ABSTRACT. A review is given of the symptoms following traumatic hospitalization experience of children and the factors which influence the way in which they behave, when they are hospitalized. The ways in which the hospitalization syndrome may be prevented are discussed, with particular emphasis on the importance of maintaining the child's relationship with the parents by having a liberal policy as regards visiting or by a rooming‐in system. Ordinary school activities, play‐therapy, occupational therapy and hospital libraries may play a very important role in preventing hospitalized children from becoming self‐absorbed. Although the hospitalization syndrome has been known for 30–35 years, we still have insufficient information about what factors make a child predisposed to develop such a syndrome
Cardiomyopathy Induced by Anthracycline‐Derivates
Authors: BROCKMEIER F. K. , ROSLAND G. A. , FINNE P. H.
Published: January 2008

ABSTRACT. Two cases of anthracycline‐induced congestive heart failure are described. Serial assessment of cardiac function during treatment showed early deterioration of the systolic time intervals of the left ventricle (LSTI) before congestive cardiomyopathy could be demonstrated by echocardiography. We recommend that the cardiac function should be assessed regularly during anthracycline therapy by systolic time intervals and echocardiography to reveal early signs of cardiotoxic effect and that anthracycline therapy should be stopped when LSTI is 0.45 or when it has increased more than 50 % compared to pretreatment values
Accuracy of anthropometric measurements in predicting symptomatic SGA and LGA neonates
Authors: Drossou V , Diamanti E , Noutsia H , Konstantinidis T , Katsougiannopoulos V
Published: January 2008

Mid‐arm circumference, mid‐arm circumference/head circumference ratio, ponderal index and skinfold thickness at five sites (biceps, triceps, quadriceps, subscapular and flank) were measured in 91 small‐for‐gestational‐age (SGA) and 101 large‐for‐gestational‐age (LGA) neonates to investigate their accuracy in identifying neonates at high risk of complications resulting from disturbed intrauterine growth. Thirty‐one of 91 SGA and 19 of 101 LGA neonates who developed hypoglycaemia and/or polycythaemia were regarded as symptomatic. Mean values of all of the anthropometric parameters differed significantly between symptomatic and asymptomatic SGA or LGA neonates. The quadriceps skinfold thickness was the most sensitive index in predicting symptomatic SGA and LGA neonates (sensitivity 0.93 and 0.95, respectively). The mid‐arm circumference was also a very sensitive index in predicting symptomatic SGA neonates (sensitivity 0.94) but its specificity was extremely low (0.20). The rest of the parameters showed lower sensitivity than quadriceps skinfold thickness associated with similarly low specificity and validity. The findings of this study indicate that the quadriceps skinfold thickness is the most reliable index for use as a screening test for clinical evaluation of SGA and LGA neonates who are likely to develop complications as a result of disturbed intrauterine nutrition.
Determinants of blood glucose variability in adolescents with insulin‐dependent diabetes mellitus
Authors: Zachrissons I , Wallensteen M , Dahlquist G
Published: January 2008

Metabolic control and blood glucose variability in children with insulin‐dependent diabetes mellitus (IDDM) during and after puberty were studied. Seventy‐two children (43M, 29F), aged 10‐19 years, with a 2‐16‐year duration of IDDM participated in the study. Fourteen of the patients were prepubertal (Tanner stage 1), 27 pubertal (Tanner 2‐4) and 31 postpubertal (Tanner 5). They performed self‐monitoring of blood glucose (SMBG) five times daily, every 2 days for 4 weeks. The SD (SDbg) for all values in each patient was calculated as a measure of blood glucose variability. Weight‐length index, linear growth velocity and Tanner stage were recorded. Hemoglobin (Hb)AIc, alkaline phosphatase and sex hormone levels in serum were analyzed. Subjectively experienced hypoglycemic episodes were recorded. HbAIc levels showed no relation to Tanner stage. SDbg was lower in stage 5 than in stages 2‐4 (p= 0.02). There was no significant correlation between HbAlc and SDbg, but the variability was significantly lower in individuals with mean blood glucose in the lower quartile compared with those in the upper three quartiles (p < 0.001). Alkaline phosphatase concentration, as a measure of growth velocity, was the main independent determinant of SDbg (r= 0.35, p < 0.005). There was an inverse correlation between levels of sex hormones and SDbg. We conclude that blood glucose variability is lower after than during puberty. This variability seems to be related to linear growth velocity or its biochemical marker.