bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of the subcutaneous reformulated triptorelin depot in children with central precocious puberty
Authors: Partsch C‐J , van Büren E , Brand M , Heger S , Sippell WG
Published: August 2010

The efficacy, safety and acceptance of newly formulated triptorelin s.c. (Decapeptyl® Depot, DDsc) was compared to triptorelin i.m. (DDim) in seven children with central precocious puberty (CPP) in a prospective study. Both formulations were given for 6 months consecutively. During both treatment periods suppression of basal and gonadotropin‐releasing hormone (GnRH)‐stimulated levels of luteinizing hormone and follicle‐stimulating hormone, suppression of sex steroids, arrest of the maturation of gonads and uterus, and slowing of bone maturation were achieved. The height standard deviation score for bone age increased significantly during DDsc treatment (‐1.33 ± 0.90 to 1.07 ± 0.92, p < 0:05). The ratio bone age/chronological age decreased significantly during both treatment periods (1.25 ± 0.24 to 1.20 ± 0.23,p < 0:05, and 1.20 ± 0.23 to 1.16 ± 0.22, p < 0:05). With the injection of DDsc in the abdominal wall, a palpable, non‐irritating resistance which gradually decreased in size occurred in one patient. With injection into the thigh no indurations were seen. No allergic reactions were encountered. Five of the patients considered DDsc therapy as more pleasant and described a definite decrease in fear of injections. All parents considered DDsc treatment as equal or better than DDim in respect to the suppression of their child's puberty. It was concluded that DDsc is equipotent to DDim in the treatment of CPP. For the majority of patients DDsc was more acceptable than DDim. The thigh is recommended for the subcutaneous application of DD.
Comparison of airway pressure‐triggered and airflow‐triggered ventilation in very immature infants
Authors: Dimitriou G , Greenough A , Laubscher B , Yamaguchi N
Published: August 2010

Failure of patient‐triggered ventilation in very immature infants may be due to the use of inappropriate triggering systems. Two types of airflow trigger were therefore compared consecutively to an airway pressure (SLE) triggering system. Each comparison was made in 10 infants, ≤28 weeks of gestation. Comparison was made of the delivered volume, trigger performance and blood gases using each system for 1 h. Both comparisons showed that the airflow triggering systems performed better: one (Draeger Babylog 8000) had a higher sensitivity (p < 0:01) and the other (Bird VIP airflow trigger), in which inflation was terminated by sensing a reduction in inspiratory flow, had a lower degree of asynchrony (p < 0:01) and a tendency to deliver higher volumes. These results suggest that triggering systems sensing airflow changes may be superior to those sensing airway pressure changes in very immature infants. The use of a mechanism to synchronize the termination of inflation to the end of the patient's inspiration may offer further advantages.
Influence of inhaled corticosteroids on growth: a pediatric endocrinologist's perspective
Authors: Allen DB
Published: August 2010

Given the increasing advocacy for the use of inhaled corticosteroids as a treatment of choice for persistent asthma, growing numbers of children are being exposed to the possible growth‐suppressing effects of glucocorticoids. Recent evidence strongly suggests that, when consistently administered at moderate doses, inhaled corticosteroids (IC) are capable of slowing growth in children. Whether such growth suppression would persist and ultimately affect final adult height remains unknown. Therapeutic goals which aim for uninterrupted inflammatory disease control rather than periodic symptom control may increase the occurrence of growth failure in children treated with IC. In this article, current information about the mechanisms of growth suppression by glucocorticoids and the effects of IC on growth is reviewed, and recommendations for designing studies to investigate the effects of drugs on growth are presented.
Psychological responses to the needle‐free Medi‐Jector® or the multidose Disetronic® injection pen in human growth hormone therapy
Authors: Verrips GH , Hirasing RA , Fekkes M , Vogels T , Verloove‐Vanhorick SP , Delemarre‐Van de Waal HA
Published: August 2010

The aim of the study was to test the hypothesis that daily administration of growth hormone using the Medi‐Jector® results in fewer adverse psychological responses than needle injection with a multidose injection pen. The Medi‐Jector is a needle‐free injection device that can deliver growth hormone subcutaneously through jet injection. The group studied consisted of 18 children aged 10 y or over who were participating in a study of the bioequivalence and bioequipotence of the administration of growth hormone through jet injection or needle injection. Previously, all subjects had received growth hormone therapy with commercially available multidose injection pens. The study was designed as a prospective, randomized, two‐period cross‐over trial. A questionnaire was used to assess psychological responses such as non‐compliance, opinion on ease of preparation, affective responses to administration and local side‐effects, as well as overall preference. In addition, the subjects kept a diary during the study. The subjects found the Medi‐Jector less offputting (p < 0:01), less painful with respect to both frequency (p <0.04) and intensity (p < 0.01) and less unpleasant (p < 0.05) than a multidose injection pen with a 28G needle (p <0.01). No difference in compliance was detected. Most subjects preferred the Medi‐Jector for future use (p < 0.05). The mean score on a 1–10 point scale (10 is excellent) was 7.9 (SD 1.4) for the Medi‐Jector and 6.8 (SD2.3) for the multidose injection pen (p <0.08). The prevalence of visible bruises each day was higher (p < 0.01) with the Medi‐Jector (2.5, SD 2.1) than with the multidose injection pen (0.7, SD 1.1), but children showed indifferent affective responses to bruising. Thirteen out of 18 subjects decided to continue therapy with the Medi‐Jector (p < 0.06). It is concluded that use of the Medi‐Jector in growth hormone therapy tends to lead to fewer adverse psychological responses than a multidose injection pen with 28G needles.
Placental transfer favours high avidity IgG antibodies
Authors: Avanzini MA , Pignatti P , Chirico G , Gasparoni A , Jalil F , Hanson LÅ
Published: August 2010

The aim of the present study was to evaluate if maternal‐foetal antibody placental transfer may be affected by antibody avidity. We compared the avidity index (AI) of IgG antibodies to tetanus toxoid (TT) and to type 3 pneumococcal antigen (Pn) in cord blood of 10 healthy term and 8 preterm infants and in their mothers' sera at delivery. In order to evaluate whether a heavier antigenic exposure may influence the placental transfer, we also studied 15 Pakistani maternal sera and cord blood pairs. TT‐ and Pn‐specific antibody AI was significantly higher in Italian and Pakistani term infants than in their mothers, while a significant difference in specific TT antibody AI, but not in specific Pn antibody AI was observed between preterm infants and their mothers. Italian and Pakistani cord blood/maternal serum pairs showed comparable values of AI. Our data suggest that high avidity antibodies preferentially cross the placenta; this seems to start early during gestation and appears to be related to the nature of the antigen to which the antibodies are directed, but not to the degree of antigenic exposure.
The use of CRIB (clinical risk index for babies) score in auditing the performance of one neonatal intensive care unit
Authors: Kaaresen PI , Døhlen G , Fundingsrud HP , Dahl LB
Published: August 2010

The CRIB (clinical risk index of babies) score was developed to overcome the disadvantages of birthweight‐specific comparisons between neonatal units. The aims of this study were to assess the ability of CRIB score compared to birthweight and gestational age to predict hospital mortality in very lowbirthweight infants and to use CRIB score in auditing one unit's performance during a prolonged time period. The charts of 335 infants with birthweight ≤ 1500g born between 1980 and 1995 were reviewed retrospectively. CRIB predicted hospital mortality significantly better than birthweight and gestation and performed equally well, whether the infants were treated with synthetic surfactant or not. When adjusting for CRIB score there was a significant improvement in the unit's performance, probably owing to the introduction of surfactant. As small samples tend to be associated with wide confidence intervals, use of CRIB is recommended in comparing risk adjusted mortality in a single unit over several years, as in this study, or between large groups of neonatal units over shorter periods.
Sexual victimization in adolescent girls (age 15–20 years) enrolled in post‐mandatory schools or professional training programmes in Switzerland
Authors: Tschumper A , Narring F , Meier C , Michaud PA
Published: August 2010

An analysis of data from the Swiss Multicenter Adolescent Survey on Health was conducted to assess the prevalence of a history of sexual victimization among a national sample of adolescent girls enrolled in schools or professional training, to estimate the number of associated psychosocial health problems, and to gain information on the effects of disclosure of the experience. A representative sample of 9268 adolescents answered a written questionnaire on health and lifestyle. Of the 3993 participating girls, 18.6% reported an experience of sexual victimization. The burden of associated psychosocial health problems was considerable, notably as regards depression, suicidal behaviour and substance misuse. Preliminary findings on the relation of disclosure and mechanisms of learned helplessness stress the need for more research on this issue. The results stress the importance of prevention programmes for adolescents and preadolescents, of physicians' awareness and training for screening and appropriate counselling, and of easy access to professional support.
Neonatal flumazenil therapy reverses maternal diazepam
Authors: Dixon JC , Speidel BD , Dixon JJ
Published: August 2010

A woman at 32 weeks' gestation with eclampsia was given 120 mg diazepam shortly before emergency caesarean section. The infant had persistent apnoea and required respiratory support. Spontaneous respiration began after intravenous flumazenil infusion was started. Diazepam and its active metabolites were assayed during and after 5 d of treatment with flumazenil.
Immunobiology of T helper cells and antigen‐presenting cells in autoimmune thrombocytopenic purpura (ITP)
Authors: Semple JW
Published: August 2010

Autoimmune thrombocytopenic purpura (AITP) is a bleeding disease in which autoantibodies are directed against the individual's own platelets, resulting in enhanced Fc‐mediated platelet destruction by macrophages in the reticuloendothelial system. Most research in AITP has focused on characterization of the autoantibodies, while little has been devoted to the cellular immune mechanisms leading to autoantibody production. This report summarizes the current state of the literature and argues that enhanced T helper cell/antigen‐presenting cell interactions in patients with AITP are the primary stimulus for the development of antiplatelet autoantibody production. Understanding these events is important for eventually identifying disease‐initiating platelet autoantigens and ultimately developing specific immunotherapies for AITP.
Short‐course oral prednisone therapy in children presenting with acute immune thrombocytopenic purpura (ITP)
Authors: Carcao MD , Zipursky A , Butchart S , Leaker M , Blanchette VS
Published: August 2010

Immune thrombocytopenic purpura (ITP) is a disorder for which management remains controversial. The ongoing goal is to define the minimal therapy required for children with acute ITP. A pilot study of short‐course oral prednisone (4 mg−1 kg−1 d−1 for 4 d with no tapering) was undertaken in 25 consecutive children with acute ITP and platelet counts under 20 × 109 1−1. Of the 25 children, 22 responded to the prednisone therapy by achieving a platelet count higher than 20 × 109 1−1 within 1 week of commencing treatment. This regimen was found to be safe, inexpensive and effective in increasing the platelet count of children to a haemostatically safe level.
Directions for research in autoimmune thrombocytopenic purpura (ITP)
Authors: Freedman J , Garvey MB , Elinder G , Blanchette VS
Published: August 2010

All attendees participated in a round‐table discussion regarding directions for research in autoimmune thrombocytopenic purpura (ITP). Suggested areas for study were grouped into five main areas: (i) improved classification of ITP identifying subsets of patients with differing clinical syndromes and response to treatment, and those more likely to have serious bleeding manifestations; identification of patients with reduced thrombopoiesis was emphasized; (ii) studies aimed at elucidating the aetiology and pathophysiology of ITP, with emphasis on distinctions between acute and chronic ITP and between patients responsive or refractory to therapy; these studies focused on measures of humoral and cellular immune dysregulation; (iii) studies of platelet function in ITP, with the intent of defining these abnormalities and correlating them with the clinical manifestations of the disease; (iv) new approaches to treatment, particularly of refractory patients; and (v) a miscellaneous group, which included development of an ITP registry, evaluation of the “burden” of disease, investigation of mood changes in ITP, etc. The discussion was not intended to be all‐inclusive, but focused on the content of other talks in this symposium. It is hoped that some of thesesuggestions will be further developed for investigation in multicentre co‐operative studies to improve the diagnosis, understanding and treatment of ITP.
The aetiology of type 1 diabetes: an epidemiological perspective
Authors: Dahlquist G
Published: August 2010

Type 1 diabetes is increasing rapidly in many parts of the Western world, most evidently in Scandinavia. A low concordance rate of insulin‐dependent diabetes mellitus among monozygotic twins clearly indicates that genetic risk factors may be necessary, but are not sufficient for the disease to occur. The strongest genetic risk markers are located in the HLA region of chromosome 6, but these DNA specificities differ in different populations. Risk genes are indicated in other chromosomes of the human genome, suggesting a complex interaction between genes and environment as the cause of the disease. The pathogenesis of the disease is proposed to be autoimmune in nature and environmental risk factors may either initiate autoimmunity or accelerate an already ongoing β‐cell destruction. Risk factors disclosed by epidemiological studies that may accelerate the pathogenetic process are: a cold environment, a high growth rate, infections and stressful life events. Risk factors that may initiate the autoimmune process include early exposure to cow's milk proteins, nitrosamines or early foetal events such as blood group incompatibility or foetal viral infections. In conclusion, population‐based epidemiological studies have helped to confirm proposed aetiological models that have arisen from experimental research. These epidemiological studies have also introduced important new findings that may reveal the complex aetiology of the disease and advance understanding closer to the ultimate goal of primary prevention.
Prediction and prevention of type 1 diabetes
Authors: Knip M
Published: August 2010

Clinical type 1 diabetes represents end‐stage insulitis resulting from progressive β‐cell destruction over an asymptomatic period that may last for years. This knowledge and recent advances in our ability to identify individuals at increased risk for clinical disease have paved the way for trials aimed at preventing or delaying the clinical onset of type 1 diabetes. Individuals at risk for type 1 diabetes can be identified by a positive family history, or by genetic, immunological or metabolic markers. These markers can also be combined to achieve a higher positive predictive value. As long as there is no effective preventive modality available for clinical use, screening for the identification of risk individuals can be considered ethically acceptable only in the context of sound research protocols. Prevention of type 1 diabetes can be implemented at three different levels, out of which primary prevention includes all strategies aimed at decreasing the risk of developing type 1 diabetes in individuals without any signs of β‐cell damage. Secondary prevention aims to reduce the incidence of type 1 diabetes by stopping β‐cell destruction in individuals with signs of such a process, while the objective of tertiary prevention is to restore β‐cell function or prevent complications in patients with overt type 1 diabetes. At present, one primary prevention trial and four comprehensive secondary prevention trials are in progress. Common features of these intervention trials are that the recruitment of patients fulfilling the inclusion criteria is time‐consuming and the trials must proceed for a long time, as clinical disease is the end point. The secondary prevention trials also require extensive screening for the identification of eligible patients. The ongoing intervention trials may, however, represent a new era in type 1 diabetes, i.e. the beginning of the end of this complicated disease.
Practical aspects of managing preschool children with type 1 diabetes
Authors: Kiess W , Kapellen T , Siebler T , Deutscher J , Raile K , Dost A , Meyer K , Nietzschmann U
Published: August 2010

Day‐to‐day variations in diet and physical exercise, large variations in the glucose response to small changes in insulin doses, and high insulin sensitivity are characteristic of preschool children with diabetes. Hence, difficulties in achieving adequate metabolic control and stable glycaemia in preschool children are common. In addition, hypoglycaemic episodes tend to be frequent and severe in this age group. Problems identifying and treating hypoglycaemia present an additional challenge for the diabetes team and for the family caring for the young child with diabetes. Specific glucose targets are provided for this age group: premeal levels of 6‐12 mmol 1−1 (110‐220 mg dl−1) with bedtime levels above 8 mmol 1−1 (140 mg dl−1). It is important to note that children who suffer severe hypoglycaemic events at a young age show evidence of subtle cognitive deficits when tested during adolescence. The question of whether or not the years before pubertal onset contribute less towards the development of diabetes‐related microvascular complications than do the years starting with the onset of puberty remains controversial. Twice‐daily or multiple insulin injections, dietary adjustments and considerations, home blood‐glucose monitoring, family education, support groups and 24‐h hotline information facilities can help to achieve good metabolic control without severe hypoglycaemia in the preschool child. In general, good metabolic control without severe hypoglycaemia can be achieved using frequent counselling and a caring team approach.
Chlamydia pneumoniae in children with acute respiratory tract infections
Authors: Normann E , Gnarpe J , Gnarpe H , Wettergren B
Published: August 2010

Children seeking medical attention for acute respiratory tract infections were investigated for evidence of Chlamydia pneumoniae infection. Blood samples were obtained from 367 children. Nasopharyngeal or throat swabs for PCR analysis (polymerase chain reaction) were taken from 360 children. Serology was found to be useful for diagnosis of infection only in children aged 5 y. Using PCR, a prevalence of 8 and 10% of C pneumoniae was found in male and female children aged < 2 y; 17 and 19%, respectively, in the age group 2‐4 y and 32 and 21%, respectively, in the age group 5–16 y. We conclude that Chlamydia pneumoniae is a common finding in young children with respiratory tract infections. Younger children were more often found to have a moderate disease, but may have been ill for a long period.
Growth hormone treatment of children with Prader‐Willi syndrome affects linear growth and body composition favourably
Authors: Lindgren AC , Hagenäs L , Müller J , Blichfeldt S , Rosenborg M , Brismar T , Ritzén EM
Published: August 2010

We have compared the growth and the body composition in children with Prader‐Willi syndrome (PWS) with and without growth hormone treatment (recombinant GH 0.1 IU/kg/day) after a 1‐y period. Twenty‐nine prepubertal children with PWS, with mean body mass index (BMI) SDS of 2.2, and 10 (control) healthy obese children with mean BMI SDS of 5.6, underwent 24‐h frequent blood sampling. Both PWS and control obese children had low and similar GH levels (0.7 /ng/l ± 0.4 SD). Serum IGF‐I levels, however, were significantly lower in children with PWS (‐1.5 SDS ± 0.8 SD vs ‐0.2 SDS ±0.8 SD). The 29 PWS children were randomized into 2 groups of 15 and 14 subjects for GH treatment and no treatment, respectively. Height velocity increased from ‐1.9 SDS to + 6.0 SDS in the treated group (p < 0:001) and decreased from ‐0.1 SDS to ‐1.4 SDS in the control PWS group during the study year. BMI decreased significantly for the treated group (+3.0 SDS to + 2.0 SDS). Relative fat mass decreased significantly, while fat‐free mass increased (p < 0:001) for the treated group. No significant changes were noticed in body composition in the control PWS group. In conclusion, the low spontaneous 24‐h GH secretion, regardless of body weight, and the exceptional response to growth hormone treatment together with the finding of low IGF‐I levels suggest that growth hormone deficiency is a common feature of PWS, as a result of hypothalamic dysfunction. Treatment with growth hormone is beneficial for the majority of PWS children.
The cardiovascular risk factor profile of Estonian school children
Authors: Grünberg H , Thetloff M
Published: August 2010

This cross‐sectional study was undertaken to assess the occurrence of conventional cardiovascular risk factors in Estonian school children after the socioeconomic changes of the early 1990s. A total of 1018 9‐, 12‐ and 15‐y‐old randomly selected children were studied for lipid and lipoprotein profiles, blood pressure, weight, height, regular smoking, physical activity and family history of premature cardiovascular disease. In 11–24 % of the children, total cholesterol levels were at or above the risk cut‐off of 5.2 mmol l‐1, 3‐5% of the children were considered to be obese and 6‐12% had blood pressure higher than the age‐ and gender‐specific 95th percentile of height. Of the 15‐y‐old girls and boys, 1% and 10%, respectively, admitted being daily smokers. Five percent of girls and 20% of boys smoked at least once a week. Ten to 18% of children reported little physical activity. According to age groups, 17‐25% of the children had a family history of premature cardiovascular disease. The occurrence of three or more risk factors simultaneously characterized only the older age group, in which 2.3% of girls and 3.5% of boys exhibited clustering of potential cardiovascular risk factors. Our findings showed a relatively low frequency of obesity and low mean blood lipid levels with a high proportion of smokers among children in late puberty, implying that preventive efforts should focus on pubertal children to prevent adverse health behaviour.
Transient red cell aplasia in siblings: a common environmental or a common hereditary factor?
Authors: Skeppner G , Forestier E , Henter J‐I , Wranne L
Published: August 2010

During the years 1987‐89, transient erythroblastopenia of childhood was diagnosed in 52 previously healthy Swedish children aged less than 4 y. Among these children there were four pairs of siblings, including one pair of identical female twins. This is a much higher familial occurrence than expected. The probability of finding 4 pairs of siblings with this disease in 50 families was estimated to be considerably less than 10–6. In the retrospectively analysed material, no environmental factor was implicated and no association with human leucocyte antigen could be proven. The twins demonstrated the disease simultaneously. Their anaemia was transient and did not recur, but showed certain features usually seen in congenital hypoplastic anaemia. The other pairs of siblings fulfilled the criteria for transient erythroblastopenia of childhood and several years elapsed between the development of the disease in siblings. Two of the fathers were reported to have had transient anaemia during their childhood. Our findings indicate that transient erythroblastopenia of childhood may involve hereditary factors, eventually demonstrating an autosomal dominant inheritance.
Changes in protein turnover, IGF‐I and IGF binding proteins in children with cancer
Authors: Attard‐Montalto SP , Camacho‐Hübner C , Cotterill AM , D'Souza‐Li L , Daley S , Bartlett K , Halliday D , Eden OB
Published: August 2010

Changes in insulin‐like growth factor‐I (IGF‐I) and insulin‐like growth factor binding proteins (IGFBPs) were correlated with protein synthesis and breakdown using [1‐ 13C]leucine before chemotherapy and during subsequent febrile neutropenia (FN) in eight children with cancer, aged 6.3–17.5 y. IGF‐I levels were similar to age‐matched controls before chemotherapy (mean ±SEM: 250 ±28 and 228 ±22 μg l‐1, respectively). During FN, IGF‐I fell to 156 ±22 /ng l ‐1(p= 0:02), and rose to 276 ±27 μ g l ‐1 with recovery at 6 months (p = 0:004). Similarly, IGFBP‐3 decreased from 4.0 ±0.2mgl‐1 before chemotherapy to 3.0 ±0.3 mgl‐1 during FN (p= 0:01), and returned to 4.1 ±0.2mgl ‐1 at 6 months (p= 0:01). IGF‐I correlated with IGFBP‐3 (r=+0:7, p <0:001). Scanning densitometry showed a decrease in IGFBP‐3 from 94 to 54% during FN, when the presence of IGFBP‐3 protease activity was observed. Compared with normal human serum, IGFBP‐2 was elevated throughout the study. IGFBP‐1 increased from 14.6 ±3.5 to 30.6 ±2.8/ngl‐1 (p = 0:004), whereas serum insulin decreased from 26.5 ±6.8 to 7.8 ±0.8 mUl‐1 (p= 0:03) before and during FN, respectively. Whilst IGF‐I and IGFBP‐3 fell, daytime growth hormone increased from 3.3 ±0.6 to 6.7±0.8mUl ‐1 (p= 0:01), and cortisol from 197 ±48 to 594±98nmoll ‐1 (p = 0:005). Albumin decreased from 47 ±2 to 38 ±2gl‐1 (p= 0:004) and improved to 47 ±2gl‐1 with recovery (p= 0:003). Protein synthesis increased from 4.5 ±0.4 to 5.0 ±0.6gkg‐1 d‐1 before chemotherapy and during FN, while protein breakdown rose from 5.4 ±0.4 to 6.3 ±0.4kg‐1d‐1. Increasing protein breakdown was related to falling IGF‐I and IGFBP‐3 levels. Modification of IGFBP‐3 by circulating proteolytic activity may alter IGF bioavailability, allowing protein synthesis to increase during periods of severe catabolic stress.
Different faces of non‐autoimmune diabetes of infancy
Authors: Attia N , Zahrani A , Saif R , Kattan HA , Sakati N , Al Ashwal A , Tamborlane WV
Published: August 2010

The aim of this report is to describe four cases of non‐autoimmune diabetes that presented in infancy. Three had transient neonatal diabetes mellitus (TNDM) with diabetic ketoacidosis at onset, followed by complete remission after several months of insulin treatment. While the fourth case was initially diagnosed as TNDM, she had renal, hepatic and pancreatic dysplasia. These cases illustrate that diabetes in infants can be difficult to diagnose and that patients with TNDM can have a recurrence of diabetes several years later.
Primary hypothyroidism, central diabetes insipidus and growth hormone deficiency in multisystem Langerhans cell histiocytosis: a case report
Authors: Rami B , Schneider U , Wandl‐Vergesslich K , Frisch H , Schober E
Published: August 2010

We report on a girl with central diabetes insipidus, growth hormone deficiency and bone lesions in multisystem Langerhans cell histiocytosis. Thickening of the pituitary stalk was detected by magnetic resonance imaging, which progressed over the course of the disease. During the observation period she developed primary hypothyroidism, which might be due to the extremely rare involvement of the thyroid gland in this disease. The girl underwent chemotherapy, which led to a regression of the Langerhans cell histiocytosis‐lesion, but the hormone deficiencies persisted and substitution had to be continued. Langerhans cell histiocytosis should be included in the differential diagnosis in cases with pituitary stalk thickening and additional hypothalamic/pituitary hormone deficiencies, and in cases of acquired primary hypothyroidism, with or without enlargement of the thyroid gland and ultrasound findings similar to thyroiditis.
The role of long chain polyunsaturated fatty acids (LCPUFA) in neonatal nutrition*
Authors: Gibson RA , Makrides M
Published: August 2010

Exciting new research has shown that both preterm and term infants can actively convert the essential fatty acids linoleic acid (LA, 18:2n‐6) and α‐linolenic acid (ALA, 18:3n‐3) to long chain polyunsaturated fatty acids (LCPUFA). However, the amount of LCPUFA being produced, particularly of docosahexaenoic acid (DHA, 22:6n‐3), may not be sufficient to meet the developmental requirement of the infant. Because DHA is a major component of retinal and brain tissues, a number of studies have been initiated to test the effect of dietary LCPUFA on neural outcomes in infants. These studies have largely involved a comparison of neural responses from infants fed standard infant formula (no LCPUFA) with infants receiving LCPUFA from either supplemented formula or breast milk. The results have been equivocal and may be due to the variety of LCPUFA supplements and formula fat blends used, differing testing techniques as well as variations in clinical trial conduct, but are clearer in preterm than term infants. Overall the results indicate a possible role for LCPUFA in neurodevelopment.
Seasonality of sudden infant death syndrome (SIDS) by age at death
Authors: Douglas AS , Helms PJ , Jolliffe IT
Published: August 2010

Seasonality of sudden infant death syndrome (SIDS) is a well‐established epidemiological finding. The purpose of the study was to determine whether this feature varied significantly with age at death. In total, 13 990 cases of SIDS in Scotland, England and Wales during 1982–1992 were studied by age group at death. Seasonality was established by fitting a sinusoidal curve and for each set of monthly data the peak position in the year and its magnitude were determined. Weighted regression revealed significant differences in peak position and amplitude of seasonal variation between those dying at ≤ 4 months and those aged ≥ 5 months at death. Those infants in the younger age group were more likely to die earlier in the winter months and had a smaller variation in seasonality. The peak (acrophase) months were January for ≤ 4 months and February for ≥ 5 months at death. Weighted regressions of peak position and amplitude on age at death had p‐values of < 0.001 and < 0.01, respectively. A log linear model relating SIDS incidence to month of birth, month of death and age was able to explain some of these findings. The findings support the hypothesis that in SIDS there may be more than one infant cohort, each of which passes through a vulnerable developmental window at different ages.
Increased number of substitutions in the D‐loop of mitochondrial DNA in the sudden infant death syndrome
Authors: Opdal SH , Rognum TO , Vege Å , Stave AK , Dupuy BM , Egeland T
Published: August 2010

The purpose of the present study was to investigate substitutions in the D‐loop of mitochondrial DNA (mtDNA) in sudden infant death syndrome (SIDS) and controls, since several observations indicate the involvement of mtDNA mutations in SIDS. These include elevated levels of vitreous humour hypoxanthine in SIDS victims, familial clustering without mendelian traits, and observations of increased sleepiness and a lower activity score in infants who later succumbed to SIDS. Eighty‐two cases of SIDS and 133 controls were investigated and the D‐loop sequences were recorded in the base‐pair range 16 055‐16 500 in the mtDNA sequence. The sequencing was carried out using the Applied Biosystems Sequenase dye terminator method and a ABD373A sequencer. The recorded D‐loop sequences were compared with the Cambridge sequence and differences were recorded as substitutions. The SIDS cases had a tendency towards a higher substitution rate in the D‐loop than the controls (p= 0:088). This observation makes it interesting to search for deleterious mutations in other locations in the mtDNA.
Insulin secretion and hepatic insulin clearance as determinants of hyperinsulinaemia in normotolerant grossly obese adolescents
Authors: Cerutti F , Sacchetti C , Bessone A , Rabbone I , Cavallo‐Perin P , Pacini G
Published: August 2010

Obesity is characterized by variable degrees of hyperinsulinaemia, which has been attributed to either β‐cell hypersecretion or reduced hepatic insulin extraction, or both. To investigate this controversial issue, a 4‐h frequently sampled i.v. glucose tolerance test (glucose dose 12.8 g m‐2) was performed in 13 normotolerant, grossly obese adolescents (10 F/3 M; 13 ± 1 y; body mass index 32 ± 0.9; pubertal stage 4–5; obesity duration 7.8 ± 3 y) and in a comparable group of 8 healthy, normal‐weight subjects. Glucose, insulin and C‐peptide time‐course were analysed by the minimal model technique, which estimates β‐cell secretion, insulin sensitivity (Si), glucose effectiveness (SG) and hepatic insulin extraction (HE). Despite similar fasting and after load glucose patterns (SGsimilar in the two groups), obese adolescents showed sustained peripheral hyperinsulinaemia (total insulin area under the concentration curve 67.2 ± 10.8 vs 19.1 ± 1.2 pmol l‐1in 240 min;p< 0:002) and a 71% reduction inSi(2.02 ± 0.33 vs 6.95 ± 1.03±104min‐1(μU ml‐1);p< 0:001). Compared with control subjects, the total amounts of prehepatic insulin secretion and posthepatic insulin delivery were also increased significantly in obese adolescents by 30% and 46%, respectively; HE was reduced by 15% during the first 30 min of the test, but recovered within the normal range during the rest of the test. In conclusion, severely obese adolescents are insulin resistant and their hyperinsulinaemia is primarily caused by β‐cell hypersecretion, whereas the reduction in insulin hepatic extraction is a transient metabolic phenomenon.
Elevated erythrocyte sedimentation rate and thrombocytosis as possible indicators of active disease in Langerhans’cell histiocytosis
Authors: Calming U , Henter J‐I
Published: August 2010

Langerhans’cell histiocytosis (LCH) is a disease with an unpredictable course and unpredictable reactivations. Since active disease may cause life‐long sequelae, early detection of reactivation is important. The usefulness of erythrocyte sedimentation rate (ESR) and thrombocytosis as indicators of disease activity in patients with LCH were examined. The mean values for ESR and platelet count for each quarter of a year were compiled. The means of all the ESR estimates (n= 76) during each quarter of a year with active disease was 21 mm h‐1, with intermediate disease activity 11 mm h‐1 and with resolution 7mmh‐1. The corresponding platelet count estimates (n= 139) were 433 × 109l‐1, 365 × 109l‐1 and 304 × 109 l‐1, respectively. In conclusion, elevated ESR and platelet count may be clinically valuable indicators of disease activity in LCH.
Measured and predicted bone mineral content in healthy boys and girls aged 6–18 years: adjustment for body size and puberty
Authors: Warner JT , Cowan FJ , Dunstan FDJ , Evans WD , Webb DKH , Gregory JW
Published: August 2010

Dual‐energy X‐ray absorptiometry (DEXA) is a rapid and precise technique for the assessment of bone mineralization in children. Interpretation of the results in growing children is complex as results are influenced by age, body size (height and weight) and puberty. Conventionally, bone mineral data derived from DEXA have been presented as an areal density [BMD; bone mineral content (BMC, g)/projected bone area (BA, cm2)], yet this fails to account for changes in BMC that result from changes in age, body size or pubertal development. Measurement of BMC and BA of the whole body, lumbar spine and left hip were made in 58 healthy boys and girls using DEXA. The relationship between BMC and BA was curvilinear, with the best fit being that of a power model (BMD = BMC/BAλ, where λ is the exponent to which BA is raised in order to remove its influence on BMC). The value of λ changed when measures of body size and puberty were taken into account (e.g. for lumbar spine from 1.66 to 1.49). Predictive formulae for BMC were produced using regression analysis and based on the variables of age, body size and pubertal development. This provides a method for interpreting the measured BMC which is independent of such variables and a constant reference range for children aged 6–18 y.
Rotaviral antibodies in the treatment of acute rotaviral gastroenteritis
Authors: Ylitalo S , Uhari M , Rasi S , Pudas J , Leppäluoto J
Published: August 2010

The efficacy of hyperimmune bovine colostrum received from cows immunized with simian rotavirus SA11 in the treatment of rotavirus gastroenteritis was compared in a randomized double‐blind trial to colostrum and ordinary milk preparations. One hundred and thirty‐five children aged 6–30 months with rotaviral gastroenteritis received either hyperimmune bovine colostrum (n= 42), ordinary colostrum (n= 42) or milk (n= 41) as a 100 ml solution four times/d for 4 d. Even though the differences were in favour of hyperimmune bovine colostrum in all the variables evaluated [greater weight gain (403 vs 343 g), shorter duration of diarrhoea (3.1 vs 3.6 d), fewer stools during 6 d (11.5 vs 13.6) and fewer stools during the first 3 d (9.3 vs 11.3)], all the differences were statistically insignificant. Differences of this size are clinically unimportant in well‐nourished immunocompetent children, but we suggest that the hyperimmune bovine colostrum tested in our trial had some effects in the treatment of acute rotaviral gastroenteritis and should be evaluated further.
Chronic non‐specific diarrhoea in childhood: how often is it iatrogenic?
Authors: Boehm P , Nassimbeni G , Ventura A
Published: August 2010

Epidemiological data, the appropriateness of the medical approach, the effectiveness of unrestricted diet and the subsequent course of chronic non‐specific diarrhoea (CNSD) were evaluated in 20 children, mean age at diagnosis 4.7 y, and mean duration of diarrhoea 24 months. A mean of 2.4 previous hospital admissions and a mean of 2.5 diagnoses other than CNSD were recorded per child before admission. On admission, 14/20 were following an elimination diet and 8/20 had an inadequate caloric intake; 16/20 had a weight/height ratio below the 50th percentile. In all cases a normal diet prescribed during hospitalization improved the diarrhoea and increased weight. A telephone interview performed 5.6 y after discharge revealed that in 10/20 of the cases, the parents were disappointed with the unrestricted diet prescribed during hospitalization. Nevertheless they reported that CNSD stopped spontaneously in a mean time of 1.7 y.
Essential fatty acid metabolism in infants with cholestasis
Authors: Socha P , Koletzko B , Swiatkowska E , Pawlowska J , Stolarczyk A , Socha J
Published: August 2010

Long‐chain polyunsaturated fatty acids are important for the growth and early development of the central nervous system. Cholestatic infants suffer from fat malabsorption and disturbed lipid metabolism and therefore may be at risk of developing polyunsaturated fatty acid depletion. The aims of this study were to determine essential fatty acid status in cholestatic infants and to study the relationship to disease severity, degree of undernutrition, antioxidant status and mode of feeding. Twenty‐four‐hour dietary records were obtained in 34 cholestatic infants, and measurements were taken of skin fold thicknesses, bilirubin levels, activities of serum alanine aminotransferase, alkaline phosphatase, gamma‐glutamyl transpeptidase, prothrombin time, serum concentrations of albumin, bile acids, total lipids, phospholipids, cholesterol, vitamins A and E, the fatty acid composition of plasma phospholipids and plasma lipid peroxides expressed as thiobarbiturate reactive substance (TBARS). Plasma phospholipid fatty acids and TBARS were also determined in 12 age‐matched healthy control infants. The cholestatic patients had very low percentage values of phospholipid essential fatty acids, particularly linoleic acid (18:2ω‐6, median 14.74% vs 20.76% in controls,p < 0:001) and its major metabolite arachidonic acid (20:4ω‐6, 6.80 vs 7.87%,p= 0:04). The patients’essential fatty acid depletion was reflected by increased levels of the non‐essential fatty acids, Mead acid (20:3ω)‐9, 0.74 vs 0.21%, p< 0:001) and palmitoleic acid (16:1ω‐7, 2.20 vs 0.43%, p< 0:001). Polyunsaturated fatty acid profiles did not differ between infants with biliary atresia (n= 13) and those with intrahepatic cholestasis (n= 21), or between 17 infants with severe malnutrition (all skin folds < 10th percentile) and mild malnutrition (at least two skin folds > 10th percentile). TBARS were significantly higher in cholestatic patients than in controls (2.74 vs 0.85 nmol ml‐1,p < 0:001) and correlated with direct (r= 0:41, p= 0:02) and total bilirubin. The daily dietary intake of linoleic acid (per 100 kcal) correlated with plasma phospholipid linoleic acid (r= 0:38,p= 0:037) and total ω‐6 fatty acids (r= 0:38,p= 0:036). Breastfed cholestatic infants (n= 6) had higher values of the ω‐3 long‐chain polyunsaturated fatty acids docosapentanoic acid (22:5ω‐3, 0.47 vs 0.28%, p= 0:0006) and docosahexanoic acid (22:6ω‐3, 2.39 vs 1.73%, p= 0:01) than formula‐fed infants, while disease severity was similar in the two groups. In conclusion, cholestatic infants are at high risk of essential fatty acid depletion, which appears to be related to fat malabsorption, hepatic essential fatty metabolism, enhanced lipid peroxidation and dietary intake.
The hypothalamic‐pituitary‐adrenal axis in preterm infants weighing ≤ 1250 g: association with perinatal data and chronic lung disease
Authors: Merz U , Pfäffle R , Peschgens Th , Hörnchen H
Published: August 2010

The hypothalamic‐pituitary‐adrenal axis (HPA) was examined in 34 ventilated preterm infants weighing ≤ 1250 g during the first week of life to evaluate the association between adrenal suppression and subsequent chronic lung disease. The second aim of the study was to detect perinatal and clinical differences between the infants with and without persistent suppression of the HPA after completion of dexamethasone treatment for chronic lung disease. To evaluate the HPA, the corticotropin‐releasing hormone stimulation test was performed, and the cortisol and adrenocorticotropic hormone (ACTH) levels were measured by radioimmunoassay. No association could be found between the synthesis of cortisol and ACTH at the end of the first week of life and the development of chronic lung disease. After treatment with dexamethasone, baseline cortisol levels < 138 nmol l‐1 were found in 12 infants (46.2%), 8 of whom (30.8%) had cortisol values below 83 nmol l‐1. The perinatal data of these patients did not differ from infants without HPA suppression. However, the infants with cortisol levels < 83 nmol l‐1 after dexamethasone showed a significantly shorter need for mechanical ventilation and supplemental oxygen (p < 0:01) and a lower incidence of chronic lung disease (p < 0:05).
Fatty acid balance studies in preterm infants fed formula milk containing long‐chain polyunsaturated fatty acids (LCP) II
Authors: Morgan C , Stammers J , Colley J , Spencer SA , Hull D
Published: August 2010

A milk formula (Prematil‐LCP) containing long‐chain polyunsaturated fatty acids (LCP) and with a fatty acid profile closely resembling breast milk has recently been introduced for preterm infants. A double‐blind randomized controlled trial was performed comparing fatty acid absorption from Prematil‐LCP (n= 10) and standard Prematil (n= 10). Formula‐fed preterm infants underwent 3 d fat balances (once full enteral feeds were established) along with a parallel human milk fed group (n= 11). Plasma samples were taken on the last day. Median total fat excretion (absorption, %) was 2.34 g kg (82.0), 2.64 g kg (82.9) and 1.65 g kg (87.8) with Prematil, Prematil‐LCP and human milk feeding, respectively. This reflected differences in the excretion and absorption of long‐chain saturated fatty acids. All groups excreted detectable LCP. LCP disappearance was higher in infants fed human milk than in those fed Prematil‐LCP, particularly for n‐6 LCP (p <0:01). Nevertheless, excreted LCP equated to <30% dietary intake, with Prematil‐LCP feeding. Plasma lipid fatty acid composition reflected differences in dietary LCP intake.
Usefulness of short‐term urine collection in the nutritional monitoring of low birthweight infants
Authors: Boehm G , Wiener M , Schmidt C , Ungethum A , Ungethüm B , Moro G
Published: August 2010

To establish adequacy of urine collection times shorter than 24 h in the metabolic monitoring of low birthweight infants, we collected urine for 24 h in 39 LBW infants during the third and fourth week of life. All urine voidings over the 24‐h period were separately collected, the volume of each sampling and the time of voiding were recorded, and 20% of the volume was removed for pooling. All individual and pooled samples were analysed for total nitrogen, urea and ammonia, a‐amino nitrogen, creatinine, sodium, potassium, calcium and phosphorus, and for each compound the ratio to 1 mol creatinine was established. Individual sample results were“pooled”to obtain 3‐, 6‐ and 12‐h period excretion and than related to the 24‐h excretion as measured in the pooled 24‐h sample. As the volume of urine obtained in any 6‐h collecting period depended on the time of sampling (06:00–12:00 h, 17.5 ± 3.1% of total; 12:00‐18:00 h, 31.6 ± 5.1% of total; 18:00‐24:00 h, 25.6 ± 3.1% of total; and 0:00‐06:00 h, 25.3 ± 2.9% of total), calculations were based on samples obtained from 18:00 to 06:00 h. The correlation between results of 3‐ and 24 h‐collection periods was weakest, while results of the 6‐h collection correlated highly with the total daily excretion (r= between 0.82 and 0.93 for the different compounds) and the correlation was only slightly better when the 12‐h collection period was considered. The correlation between the mean molar substrate/creatinine ratio of all individual samples of a 24‐h collecting period and the and total daily excretion of the respective substrate was weaker (r= between 0.46 and 0.76 for the different compounds) than the correlation between the results of a 6‐h collecting period and the daily excretion is not as stable than in later life. The data indicate that 6‐h urine sampling may be sufficient for metabolic monitoring of LBW infants. By contrast, urinary substrate/ creatinine ratios are not good markers of the daily excretions of the respective substrate during the first weeks of life.
Early detection of necrotizing enterocolitis by gastrointestinal tonometry
Authors: Hatherill M , Tibby SM , Denver L , Marsh MJ , Murdoch IA
Published: August 2010

The diagnosis of necrotizing enterocolitis (NEC) in neonates has traditionally depended on a combination of clinical signs, biochemical parameters and radiological changes. The measurement of intramucosal pH by gastrointestinal tonometry provides a simple means of long‐term monitoring which may detect the development of NEC before conventional techniques. We present our experience of tonometry in two‘at risk’term neonates with Hypoplastic Left Heart Syndrome.