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Aim: We aimed to evaluate the occurrence of, and risk factors for precocious and early puberty in a retrospective cohort study of girls with shunted infantile hydrocephalus., Methods: The study population comprised 82 girls with infantile hydrocephalus, born between 1980 and 2002, and treated with a ventriculoperitoneal shunt. Data were available for 39 girls with myelomeningocele and 34 without. Medical records were analysed regarding clinical data and timing of puberty. Precocious and early puberty was defined as the appearance of pubertal signs before 8 years and 0 months and 8 years and 9 months, respectively., Results: Median age at last admission was 15.8 years (range 10.0-18.0). In total, 15 girls (21%) had precocious puberty, and another 21 (29%) had early puberty. Three or more shunt revisions had been performed in 26/36 girls with early or precocious puberty and in 3/37 girls without (p = 0.01). The number of shunt revisions correlated negatively with age at the start of puberty in the girls with myelomeningocele (Spearman's correlation coefficient = -0.512, p = 0.001)., Conclusion: Girls with shunted infantile hydrocephalus have a high risk of precocious or early puberty. Repeated shunt revisions seemed to be associated with early puberty., (© 2024 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Aim: To investigate the prevalence of vitamin D deficiency among children with non-haematological malignancies and to explore possible causes of low vitamin D levels among these patients., Methods: We performed a cross-sectional study of 458 children diagnosed with solid tumours, brain tumours, non-Hodgkin lymphoma or Hodgkin disease at the University Children's Hospital, Uppsala, Sweden. Serum 25-hydroxyvitamin D and parathyroid hormone levels were measured in samples taken at the time of cancer diagnosis and related to clinical data. Vitamin D deficiency was defined as a 25-hydroxyvitamin D level below 50 nmol/L., Results: The prevalence rate of vitamin D deficiency among children with non-haematological malignancies was 41%. There was no association between sex or diagnosis and vitamin D status. Vitamin D deficiency was more common among school children than preschool children (51% vs. 24%). Older age, season outside summer, and a more recent calendar year were significant predictors of lower 25-hydroxyvitamin D. There was a significant, albeit weak, negative correlation between 25-hydroxyvitamin D and parathyroid hormone., Conclusion: Vitamin D deficiency is common among children diagnosed with cancer, particularly among school-aged children diagnosed outside summer. The prevalence appears to be increasing, underlining the need for adequate replacement of vitamin D in these patients., (© 2021 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Aim: To investigate whether a high birthweight was associated with an increased proportion of body fat or with impaired glucose tolerance in adulthood., Methods: Our cohort comprised 27 subjects with birthweights of 4500 g or more, and 27 controls with birthweights within ±1 standard deviation scores, born at Uppsala University Hospital 1975-1979. The subjects were 34-40 years old at the time of study. Anthropometric data was collected, and data on body composition was obtained by air plethysmography and bioimpedance and was estimated with a three-compartment model. Indirect calorimetry, blood sampling for fasting insulin and glucose as well as a 75 g oral glucose tolerance test were also performed. Insulin sensitivity was assessed using homoeostasis model assessment 2 and Matsuda index., Results: There were no differences in body mass index, body composition or insulin sensitivity between subjects with a high birthweight and controls., Conclusion: In this cohort of adult subjects, although limited in size, those born with a moderately high birthweight did not differ from those with birthweights within ±1 standard deviation scores, regarding body composition or glucose tolerance., (©2019 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aim: To analyse levels and profiles of autism symptoms in children with Down Syndrome (DS) with and without diagnosed autism spectrum disorder (ASD) and to specifically study the groups with severe Intellectual Disability (ID)., Methods: From a population-based cohort of 60 children with DS (age 5-17 years) with 41 participating children, scores obtained from the Autism Diagnostic Observation Schedule (ADOS) Module-1 algorithm were compared between those with and without diagnosed ASD. Children with DS and ASD were also compared to a cohort of children with idiopathic ASD, presented in the ADOS manual., Results: Children with DS and ASD had significantly higher ADOS scores in all domains compared to those without ASD. When the groups with DS, with and without ASD, were restricted to those with severe ID, the difference remained. When the children with DS and ASD and the idiopathic autism group were compared, the ADOS profiles were similar., Conclusion: A considerable proportion of children with DS has ASD, but there is also a group of children with DS and severe ID without autism. There is a need to increase awareness of the high prevalence of autism in children with DS to ensure that appropriate measures and care are provided., (©2019 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aim: We investigated the severities and profiles of intellectual disability (ID) in a population-based group of children with Down syndrome and related the findings to coexisting autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD)., Methods: There were about 100 children with Down syndrome living in Uppsala County, Sweden, at the time of the study who all received medical services from the same specialist outpatient clinic. The 60 children (68% male) were aged 5-17 years at inclusion: 41 were assessed within the study and 19 had test results from previous assessments, performed within three years before inclusion. We compared two age groups: 5-12 and 13-18 years old., Results: Of the 60 children, 49 were assessed with a cognitive test and the 11 children who could not participate in formal tests had clinical assessments. Mild ID was found in 9% of the older children and in 35% of the younger children. Severe ID was found in 91% of the older children and 65% of the younger children. Verbal and nonverbal domains did not differ., Conclusion: Intellectual level was lower in the older children and patients with Down syndrome need to be followed during childhood with regard to their ID levels., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aim: This study investigated whether a high birth weight was associated with increased risk factors for cardiovascular disease when Swedish adults reached 34-40., Methods: We studied 27 subjects born at Uppsala University Hospital in 1975-1979, weighing at least 4500 g, and compared them with 27 controls selected by the Swedish National Board of Welfare with birth weights within ±1 standard deviations scores and similar ages and gender. The study included body mass index (BMI), blood pressure, lipid profile, haemoglobin A1c (HbA1c), C-reactive protein (CRP) and high-frequency ultrasound measurements of intima-media thickness, intima thickness (IT) and intima:media ratio of the carotid and radial arteries., Results: Subjects with a high birth weight did not differ from controls with regard to BMI, blood pressure, lipid profile, high-sensitivity CRP, HbA1c or carotid artery wall dimensions. However, their radial artery intima thickness was 37% greater than the control group and their intima:media ratio was 44% higher., Conclusion: Our findings indicate that a high birth weight was associated with increased radial artery intima thickness, but not with other investigated cardiovascular risk factors, at 34-40 years of age. The clinical implications of these findings should be investigated further, especially in subjects born with a very high birth weight., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Unlabelled: Very few high-quality studies on paediatric reference intervals for general clinical chemistry and haematology analytes have been performed. Three recent prospective community-based projects utilising blood samples from healthy children in Sweden, Denmark and Canada have substantially improved the situation., Conclusion: The present review summarises current reference interval studies for common clinical chemistry and haematology analyses., (©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

During the past few decades age at death for individuals with Down syndrome (DS) has increased dramatically. The birth frequency of infants with DS has long been constant in Sweden. Thus, the prevalence of DS in the population is increasing. The aim of the present study was to analyze mortality and causes of death in individuals with DS during the period 1969-2003. All individuals with DS that died between 1969 and 2003 in Sweden, and all individuals born with DS in Sweden between 1974 and 2003 were included. Data were obtained from the Swedish Medical Birth Register, the Swedish Birth Defects Register, and the National Cause of Death Register. Median age at death has increased by 1.8 years per year. The main cause of death was pneumonia. Death from congenital heart defects decreased. Death from atherosclerosis was rare but more frequent than reported previously. Dementia was not reported in any subjects with DS before 40 years of age, but was a main or contributing cause of death in 30% of the older subjects. Except for childhood leukemia, cancer as a cause of death was rare in all age groups. Mortality in DS, particularly infant mortality, has decreased markedly during the past decades. Median age at death is increasing and is now almost 60 years. Death from cancer is rare in DS, but death from dementia is common., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: Children with myelomeningocele (MMC) run an increased risk of developing early or precocious puberty (E/PP)., Aim:   To identify risk factors for E/PP in boys with MMC., Methods: Boys born between 1970 and 1992, treated for MMC at the University Children's Hospital, Uppsala, were identified. Thirty-eight boys were eligible to be included. Medical records were examined retrospectively. Early puberty was defined as pubertal signs before the age of 10 years and 2 months. Precocious puberty was defined as the appearance of these signs before 9 years of age. Increased intracranial pressure perinatally was defined as wide sutures, bulging fontanelles and increased/increasing head circumference at birth and/or during the first week after birth. Early brainstem dysfunction was defined as severe and persistent feeding and respiratory problems before the age of 3 months despite proper control of the hydrocephalus., Results: Of the 38 boys, 8 (21%) had E/PP, which was strongly associated with increased intracranial pressure perinatally and also with early brainstem dysfunction. Multivariate regression analysis showed early brainstem dysfunction to have the highest explanatory value regarding the occurrence of early puberty., Conclusion: Increased intracranial pressure perinatally and brainstem dysfunction early in life are strong predictors of E/PP in boys with MMC., (© 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.)

Objective: Down syndrome (DS) is associated with short stature and psychomotor delay. We have previously shown that growth hormone (GH) treatment during infancy and childhood normalizes growth velocity and improves fine motor skill performance in DS. The aim of this study was to investigate late effects of early GH treatment on growth and psychomotor development in the DS subjects from the previous trial., Design: Twelve of 15 adolescents with DS (3 F) from the GH group and 10 of 15 controls (5 F) participated in this follow-up study. Fifteen other subjects with DS (6 F) were included as controls in anthropometric analyses. Cognitive function was assessed with the Leiter International Performance Scale-Revised (Leiter-R) and selected subtests of the Wechsler Intelligence Scale for Children, Third edition (WISC-III). The Bruininks-Oseretsky Test of Motor Proficiency, Second edition (BOT-2), was used to assess general motor ability., Results: Although early GH treatment had no effect on final height, the treated subjects had a greater head circumference standard deviation score (SDS) than the controls (-1.6 SDS vs. -2.2 SDS). The adolescents previously treated with GH had scores above those of the controls in all subtests of Leiter-R and WISC-III, but no difference in Brief IQ-score was seen between the groups. The age-adjusted motor performance of all subjects was below -2 SD, but the GH-treated subjects performed better than the controls in all but one subtest., Conclusion: The combined finding of a greater head circumference SDS and better psychomotor performance indicates that DS subjects may benefit from early GH treatment.

Aim: It has been demonstrated that females born large for gestational age (LGA) in weight but not length are at increased risk of being obese at childbearing age. We addressed the question whether women with gestational diabetes mellitus (GDM) are at increased risk of giving birth to such infants., Methods: Birth characteristics of 884,267 infants of non-diabetic mothers and 7817 of mothers with GDM were analysed. LGA was defined as birth weight or birth length >2 standard deviation scores for gestational age. Multiple logistic regression analysis was performed., Results: The odds ratio (OR) for a woman with GDM to give birth to an LGA infant that was heavy alone was four times increased (OR: 3.71, 95% CI: 3.41-4.04). Furthermore, in the population of mothers giving birth to LGA infants, the proportion heavy alone was 68% in the group of women with GDM compared with 64.4% in the group of non-diabetic women. The risks were independent of gender of the foetus., Conclusion: Women with GDM have an almost four times higher risk of delivering an LGA infant that is heavy alone. The noted disproportion between weight and length in infants of such mothers may have an impact on the risk of later obesity.

Aim: Down syndrome (DS) is frequently associated with thyroid dysfunction. The aim of this study was to investigate the blood concentration of thyrotropin (TSH) observed at neonatal screening of infants with DS and its possible association with development of hypothyroidism during childhood., Methods: TSH levels from neonatal screening of 73 children (34 F) with DS born in 1986-1996 were studied retrospectively and compared with those of controls. The DS children were followed up regarding thyroid function to the age of 10 years in this descriptive study., Results: The DS infants had a higher mean TSH level and a higher TSH standard deviation score (SDS) than controls (7.0 +/- 7.45 mU/L vs. 3.9 +/- 2.43 mU/L and 1.1 +/- 2.67 vs. 0, respectively). The differences were mainly attributable to higher values in the male DS children. The TSH level at screening did not predict thyroid dysfunction during childhood., Conclusion: Infants with DS, especially boys, showed elevated levels of TSH at neonatal screening, indicating the occurrence of mild hypothyroidism already in early life. The TSH levels could not predict development of manifest thyroid disease later in childhood.

Aims: To study if there is a change in paediatric overweight/obesity prevalence from 1982 to 2002 in a population with a high proportion of post-graduate education., Design: Two samples of children in Uppsala County, Sweden, were compared: children who were 4, 10 and 16 year old in 1982; or 4, 10 and 16 year old in 2002. Mean BMI (in the lowest 10%, middle 50% and highest 10%) and ISO-BMI ('age adjusted BMI') cut-off values were calculated in each age and gender group., Results: Using the mean BMI or ISO-BMI cut-off values, the BMI-distribution shifted from 1982 to 2002. More 4- and 10-year-old girls and boys were overweight/obese, although this shift was larger in girls. No shift was seen in the 16-year-olds, only the middle 50% group in the 16-year-old girls had a slight increase of their mean BMI. In the 2002 4-year-old, and both 10-year-old samples, a higher proportion of the girls were overweight/obese compared to the boys, but no difference was seen in the 16-year-old sample., Conclusion: Young children, especially girls, have become much more overweight/obese during the past 20 years, despite a high proportion of post-graduate education in the population. The lack of major change in 16-year-olds may suggest a rather recent change in the children's environment/lifestyle.

Aim: To analyse if females born large for gestational age (LGA) have an increased risk to give birth to LGA infants and to study anthropometric characteristics in macrosomic infants of females born LGA., Methods: The investigation was performed as an intergenerational retrospective study of women born between 1973 and 1983, who delivered their first infant between 1989 and 1999. Birth characteristics of 47,783 females, included in the Swedish Birth Register both as newborns and mothers were analysed. LGA was defined as >2 SD in either birth weight or length for gestational age. The infants were divided into three subgroups: born tall only, born heavy only and born both tall and heavy for gestational age. Multiple logistic and linear regression analyses were performed., Results: Females, born LGA with regard to length or weight, had a two-fold (adjusted OR 1.96, 95% Cl 1.54-2.48) increased risk to give birth to an LGA infant. Females, born LGA concerning weight only, had a 2.6 (adjusted OR 2.63, 95%, 1.85-3.75) fold increased risk of having an LGA offspring heavy only and no elevated risk of giving birth to an offspring that was tall only, compared to females born not LGA. In addition, maternal obesity was associated with a 2.5 (adjusted OR 2.56, 95%, 2.20-2.98) fold increased risk of having an LGA newborn, compared to mothers with normal weight., Conclusion: Females, born LGA, have an increased risk to give birth to LGA infants, compared to mothers born not LGA. Maternal overweight increases this risk even further.

Aim: To investigate energy substrate production and its hormonal regulation in infants born small for gestational age., Methods: Eleven infants, aged 24.4 +/- 5.3 hour, were studied following a fast of 4.0 +/- 0.6 hour. Gestational age was 35.4 +/- 2.8 weeks and birth weight 1804 +/- 472 g (<-2 SD). Rates of glucose production and lipolysis were analyzed using [6,6-(2)H(2)]-glucose and [2-(13)C]-glycerol., Results: Plasma levels of glucose and glycerol were 4.1 +/- 1.1 mmol x L(-1) and 224 +/- 79 micromol x L(-1), respectively. Glucose appearance averaged 30.3 +/- 8.2 and glucose production rate 21.1 +/- 6.1 micromol x kg(-1) x minutes(-1). Glycerol production rate was 5.6 +/- 1.6 micromol x kg(-1) x minutes(-1), correlating strongly to birth weight (r = 0.904, p < 0.001). Of the glycerol produced, 55 +/- 22% was converted to glucose, corresponding to 8 +/- 3% of the glucose production., Conclusions: Even though the infants could produce energy substrates, lipolysis was reduced and the glucose production was in the low end of the normal range compared with infants born appropriate for gestational age. The correlation between glycerol production and birth weight indicates that lipolysis depends on the amount of stored fat. Data on insulin and insulin-like growth factor binding protein 1 support the view that insulin sensitivity in these infants is reduced in the liver but increased peripherally.

Background: Patients with Down syndrome are prone to autoimmune diseases which also occur in the recessive disease autoimmune polyendocrine syndrome type I (APS I). Since this disease is caused by mutations in the gene AIRE on chromosome 21, one might speculate that altered expression of AIRE contributes to autoimmune disease in Down syndrome., Aim: To study the prevalence of 11 well-defined autoantibodies, five of which are specific for APS I, associated with various manifestations of APS I in patients with Down syndrome., Methods: Sera from 48 patients with Down syndrome were analysed. Autoantibodies against 21-hydroxylase, 17alpha-hydroxylase, side-chain cleavage enzyme, aromatic L-amino acid decarboxylase, cytochrome P4501A2, tyrosine hydroxylase, tryptophan hydroxylase, glutamic acid decarboxylase 65, tyrosine phosphatase IA-2 and transglutaminase were analysed using an immunoprecipitation assay, and thyroid peroxidase autoantibodies were measured using a haemagglutination assay., Results: Seven of 48 patients had elevated titres of autoantibodies: one against 21-hydroxylase, three against aromatic L-amino acid decarboxylase, one against cytochrome P4501A2, one against glutamic acid decarboxylase 65 and one against tyrosine phosphatase IA-2. None of the patients had clinical or laboratory signs of disease coupled to the respective autoantibody., Conclusion: Four patients with Down syndrome had autoantibodies hitherto regarded as unique for APS I, which may suggest a dysregulation of AIRE.

Objective: Intrauterine growth restriction (IUGR) is a common complication of pregnancy. There are many possible aetiologic factors of maternal, placental and/or fetal origin. Often there is no known explanation. The aim of this study was to investigate whether a reduction in maternal energy substrate production could be one of the factors involved in IUGR., Design: Measurement of maternal energy substrate production and glucoregulatory hormones in women with growth-restricted fetuses., Settings: University Hospital, Uppsala, Sweden., Population: Ten healthy pregnant women with IUGR were compared with eight recently reported healthy women with normal pregnancies. The women were studied at 35.4+/-1.6 weeks of gestation after an overnight fast., Methods: Rates of glycerol and glucose production were analysed by gas chromatography/mass spectrometry following constant-rate infusion of [1,1,2,3,3-(2)H5]glycerol and [6,6-(2)H2]glucose., Main Outcome Measure: Third trimester glycerol and glucose production., Results: Glycerol production, reflecting lipolysis, was lower in the women with IUGR than in those with normal pregnancies, 2.36+/-0.58 versus 3.06+/-0.66 micromol kg-1 minute-1 (P=0.033), whereas there was no difference in rate of glucose production (glucose production rate [GPR]), 12.1+/-1.5 versus 13.2+/-1.5 micromol kg-1 minute-1 (P=0.23). Plasma glycerol levels were increased in the women with IUGR (P=0.008)., Conclusions: Lipolysis is lower in pregnancies complicated by IUGR as compared with normal pregnancies. Increased lipolysis during pregnancy provides substrate for maternal energy metabolism, which spares glucose for the fetus. A reduced maternal production of energy substrate could be one of several factors underlying IUGR. A lack of relationship between insulin levels and either lipolysis or GPR suggests defective regulation of energy substrate production in this group of pregnant women.

Aim: To describe spontaneous cortisol secretion in children after autologous bone marrow transplantation (BMT) for acute leukaemia and lymphoma., Methods: Spontaneous cortisol secretion was analysed in 39 children before and after BMT. Thirteen patients were conditioned with chemotherapy only (group 1), and 26 patients also with total body irradiation (TBI). In the TBI group, 14 patients had received no additional irradiation (group 2), whereas 12 patients had received cranial irradiation (CRT) previously (group 3)., Results: Before BMT, in comparison with group 1, mean morning cortisol was significantly lower in group 2 (252 vs 415 mmol/l, p = 0.004), but not in group 3 (vs 312 mmol/l, p = 0.12). There was no change in group 1 six months after BMT (to 379 nmol/l), whereas morning cortisol increased significantly in group 2 and group 3 (to 386 and 343 nmol/l, respectively; p < 0.05). The change in mean morning cortisol correlated negatively with pretransplant morning cortisol (r = -0.63, p < 0.001). Neither TBI nor CRT were associated with changes in morning cortisol., Conclusion: Spontaneous cortisol secretion is maintained after BMT irrespective of whether cranial or total body irradiation has been given or not.

Aim: Exclusive breastfeeding increases survival and optimizes growth of low-birthweight (LBW) infants. If supported, mothers can overcome the unique difficulties associated with breastfeeding from birth to 6 mo. We tested the efficacy of postnatal peer counselling among first-time mothers that aimed to increase exclusive breastfeeding of term LBW infants., Methods: In a Manila hospital, 204 mothers were randomized into three groups. Two intervention groups receiving home-based counselling visits, one by counsellors trained in breastfeeding counselling (n=68), the other by counsellors trained in general childcare (n=67), were compared with a control group of mothers (n=69) who did not receive counselling., Results: Eighty-eight per cent of the participating pairs completed the trial. At 6 mo, 44% of the breastfeeding counselled mothers, 7% childcare-counselled mothers and none of the mothers in the control group were exclusively breastfeeding. More mothers in the breastfeeding counselled group than in the other groups were still breastfeeding at 6 mo. Twenty-four infants who were exclusively breastfed for 6 mo did not have any diarrhoea. All groups had improved mean weight-for-age Z-scores at 6 mo., Conclusion: This study has provided fundamental evidence of successful intervention to achieve 6 mo of exclusive breastfeeding among term LBW infants. By improving health outcomes, enhanced breastfeeding offers a distinct possibility of disrupting the intergenerational cycle of undernourished women giving birth to LBW infants.

Background: During pregnancy, metabolic adaptation takes place in the mother to provide for the supply of substrates to the growing fetus., Objective: To determine rates and endocrine regulation of lipolysis and glucose production (GPR) in late pregnancy., Design: Energy substrate production was measured in healthy pregnant women by use of stable isotope-labelled compounds., Setting: University Hospital, Uppsala, Sweden., Sample: Eight healthy non-obese, non-smoking women with normal pregnancies were studied at 33-36 weeks of gestation after an overnight (12-14 hours) fast., Methods: Rates of glycerol and glucose production were analysed by gas chromatography/mass spectrometry following constant rate infusion of [1,1,2,3,3-(2)H(5)]-glycerol and [6,6-(2)H(2)]-glucose., Main Outcome Measure: Glycerol and glucose production in the third trimester., Results: The mean rate of glycerol production, reflecting lipolysis, was 3.06 (0.66) and the mean GPR was 13.2 (1.5) micromol kg(-1) minute(-1) [2.38 (0.27) mg kg(-1) minute(-1)]. There was a correlation between rate of glycerol production and GPR (r = 0.75, P = 0.033). Fasting insulin levels correlated inversely with both the rate of glycerol production (r = -0.85, P = 0.008) and GPR (r = -0.78, P= 0.021)., Conclusions: Our results show that lipolysis is markedly increased during late pregnancy compared with reported data for non-pregnant women. The data also confirm the occurrence of an increased GPR in pregnant women. The finding of a correlation between rate of glycerol production and GPR corroborates the view that lipolysis promotes gluconeogenesis. Although late gestation is associated with insulin resistance, the results show that insulin plays a regulatory role both in lipolysis and glucose production.

Unlabelled: Glucose production and lipolysis were investigated in teenage girls with anorexia nervosa using glucose and glycerol labelled with stable isotopes. The production of energy substrates were also maintained in the very underweight patients who showed higher relative rates of substrate mobilization compared to those who had gained some weight., Conclusion: The investigation shows that glucose production, necessary to provide fuel for the central nervous system, is also maintained in starving patients with anorexia nervosa.

Background: Girls adopted from developing countries often have early or precocious puberty, requiring treatment with gonadotrophin-releasing hormone (GnRH) analogues. During such treatment, decreased growth velocity is frequent., Aim: To study whether the addition of growth hormone (GH) to GnRH analogue treatment improves final height in girls with early or precocious puberty., Methods: Forty-six girls with early or precocious puberty (age < or =9.5 y) adopted from developing countries were randomized for treatment for 2-4 y with GnRH analogue, or with a combination of GH and GnRH analogue., Results: During treatment, the mean growth velocity in the GH/GnRH analogue group was significantly higher compared to the control group. Combined GH/GnRH analogue treatment resulted in a higher final height: 158.9 cm compared to 155.8 cm in the GnRH analogue-treated group. Three out of 24 girls (13%) in the combined group and nine of the 22 girls (41%) treated with GnRH analogue alone attained a final height below -2 standard deviation scores (SDS)., Conclusion: The difference between the two groups is statistically significant, and possibly of clinical importance. A future challenge is to identify a subgroup with clinically significant advantage of GH addition to GnRH analogue treatment. Being very short on arrival in Sweden and being short and young at start of treatment are possible indicators.

Crystals of germanium-doped rubidium titanyl phosphate, Rb(2)(Ti)(Ge(0.121)Ti(0.879))O(2)(PO(4))(2) (GeRTP#1) and Rb(2)(Ge(0.125)Ti(0.875))(Ge(0.225)Ti(0.775))O(2)(PO(4))(2) (GeRTP#2), have been structurally characterized from X-ray diffraction data at room temperature. In addition, a third structure, Rb(2)(TiO)(2)(PO(4))(2) (RTP), has been reinvestigated. The exchange of titanium for germanium results in a less distorted octahedral coordination around the two crystallographically independent titanium sites. Additionally, rubidium split-cation positions have been found in these doped RTP crystals. Dielectric measurements show that the phase-transition temperature, T(c), decreases with increasing germanium concentration, and a direct correlation between the room-temperature split of the rubidium cations and T(c) has been discovered. General trends regarding the relationship between the room-temperature structures of KTP-like compounds and their T(c) values are discussed.

The idea that psychotherapists' feelings may reflect some aspect of the content in the patients' material has long been clinically accepted but on the whole poorly systematically studied. The aim of this study was to analyse associations between relationship episodes told by patients at evaluation interviews, and therapists' subsequent feelings towards the patients. In total, 28 psychotherapies with nine psychotherapists were studied. Before therapy started, the clients were interviewed separately by the eventual therapist and a second interviewer and six relationship episodes were written down by the interviewers. During the therapy, the therapists reported their feelings on a 'feeling checklist' after each therapy session. In a first analysis, the relationship episodes were categorized according to the CCRT system. The results indicated only scattered associations between CCRT categories and therapist feelings. The results were, however, difficult to interpret as it was found that the therapists' feeling patterns were quite homogenous for each therapist. Considering this, qualitative analyses were made of six therapies carried out by two therapists. These analyses revealed different but theoretically plausible patterns between the feelings attributed to the persons in the patients' relationship episodes and the therapists' subsequent feelings towards the patients. The results were interpreted as a confirmation of the purported relations between patient relationship episodes and therapist feelings, but also as pointing to the need to develop the understanding of these patterns. It seems particularly important to emphasize the importance of the therapist's own habitual feeling patterns when the impact of the patient's internalized relationship patterns on countertransference reactions is evaluated.

Unlabelled: Metabolic control often deteriorates during puberty in girls with insulin-dependent diabetes. It is well accepted that there is an abnormality in the growth hormone (GH)-insulin-like growth factor-I (lGF-I) axis in these girls, resulting in reduced IGF-I levels and elevated GH. As GH antagonizes insulin, attempts have previously been made to reduce excess GH secretion through anticholinergic treatment. However, most of these studies have been performed on adult patients. The aim of the present study was to evaluate the effects of 12 wk of oral anticholinergic treatment with Pirenzepine, 100 mg twice daily, in 16 adolescent girls with diabetes. Serum samples of IGF-I, glycated haemoglobin and fasting IGF-binding protein 1 were analysed at initiation and after 3, 8 and 12 wk of Pirenzepine therapy. Nocturnal urinary GH excretion was also examined. Glycated haemoglobin declined significantly after 3 wk of Pirenzepine therapy (9.8 +/- 0.18 vs 9.2 +/- 0.17; p < 0.001) and was still improved at the end of the study. Unexpectedly, nocturnal urinary GH excretion did not change. Serum IGF-I continuously increased during the study, while IGF-binding protein 1 levels were not significantly altered., Conclusion: Anticholinergic treatment with Pirenzepine improves glycaemic control in adolescent girls with diabetes. Although nocturnal urinary GH excretion was unchanged there may still be changes in pituitary GH secretion to explain the improvement. Effects of Pirenzepine on gastrointestinal motility can represent other possible mechanisms behind the improved metabolic control.

Girls adopted from developing countries often have early or precocious puberty, requiring treatment with gonadotropin-releasing hormone (GnRH) analogues. During such treatment decreased growth velocity is frequent. The aim of this investigation was to study whether the addition of growth hormone (GH) to GnRH analogue treatment improves height velocity and final height in girls with early or precocious puberty. Forty-six girls with early or precocious puberty adopted from developing countries were randomized for treatment with GnRH analogue or a combination of GH and GnRH analogue. After 2 y of treatment the mean growth in the GH/GnRH analogue group was significantly higher, 14.6 cm, compared to 10.9 cm in the control group. The increase in bone age did not differ, while the difference in predicted adult height increased by 2.7 cm in favour of the combination group. Although data on final height are not yet available, combined GH/GnRH analogue treatment for 2 y resulted in a higher growth velocity and predicted final height compared to GnRH analogue treatment alone.

This study was undertaken to investigate the prevalence of coeliac disease in children and adolescents with Turner syndrome. Eighty-seven children and adolescents with Turner syndrome were screened for IgA-antiendomysium antibodies (EMA) and IgA-antigliadin antibodies (AGA), 5% (4/87) being found to be EMA-positive, and 15% (13/87) to have AGA levels above normal. Of the 10 patients who were either AGA- or EMA-positive and further investigated with intestinal biopsy, four manifested villous atrophy (i.e. all three of the EMA-positive patients, but only one of the seven AGA-positive patients). The results suggest EMA-positivity to be a good immunological marker for use in screening for coeliac disease, and such screening to be justified in patients with Turner syndrome.

The aims of this study were to evaluate the efficacy and safety of different doses of growth hormone (GH) treatment in prepubertal short children born small-for-gestational-age (SGA). Forty-eight children born SGA from Sweden, Finland, Denmark and Norway were randomly allocated to three groups: a control group of 12 children received no treatment for 2 y, one group was treated with GH at 0.1 IU/kg/d (n=16), and one group was treated with GH at 0.2 IU/kg/d (n=20). In total 42 children completed 2 y of follow-up, and 24 children from the treated groups completed 3 y of treatment. Their mean (SD) age at the start of the study was 4.69 (1.61) y and their mean (SD) height was -3.16 (0.70) standard deviation scores (SDS). The children remained prepubertal during the course of the study. No catch-up growth was observed in the untreated group, but a clear dose-dependent growth response was found in the treated children. After the third year of treatment, the group receiving the higher dose of GH, achieved their target height. The major determinants of the growth response were the dose of GH used, the age at the start of treatment (the younger the child, the better the growth response) and the family-corrected individual height deficit (the higher the deficit, the better the growth response). Concentration of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 increased during treatment. An increase in insulin levels was found without negative effects on fasting glucose levels or glycosylated haemoglobin levels. GH treatment was well tolerated. In conclusion, short prepubertal children born SGA show a dose-dependent growth response to GH therapy, and their target height SDS can be achieved within 3 y of treatment given GH at 0.2 IU/kg/d. However, the long-term benefit of different regimens of GH treatment in children born SGA remains to be established.

Chemical synapses convey impulses at high frequency by exocytosis of synaptic vesicles. To avoid failure of synaptic transmission, rapid replenishment of synaptic vesicles must occur. Recent molecular perturbation studies have confirmed that the recycling of synaptic vesicles involves clathrin-mediated endocytosis. The rate of exocytosis would thus be limited by the capacity of the synaptic clathrin machinery unless vesicles could be drawn from existing pools. The mobilization of vesicles from the pool clustered at the release sites appears to provide a mechanism by which the rate of exocytosis can intermittently exceed the rate of recycling. Perturbation of synapsins causes disruption of vesicle clusters and impairment of synaptic transmission at high but not at low frequencies. Both clathrin-mediated recycling and mobilization of vesicles from the reserve pool are thus important in the replenishment of synaptic vesicles. The efficacy of each mechanism appears to differ between synapses which operate with different patterns of activity.

The extent to which autoimmunity contributes to thyroid dysfunction in individuals with Down syndrome (DS) has not been clarified. In this study, we used the same highly sensitive method to detect both thyroid autoantibodies (thyroglobulin and thyroid peroxidase autoantibodies) in 70 children (32 M and 38 F) with DS, mean age 10.5 y (range 1-19 y). Twenty-seven (39%) of the patients were found to have thyroid autoantibodies, the prevalence of antibody positivity increasing with age. Of the 17 (24%) of the series who were hypothyroid (i.e. high basal TSH level and a low total- or free-T4 level), 11 had thyroid autoantibodies, and another 6 with thyroid autoantibodies became hypothyroid during 13-35 months of follow-up. Thus, the findings suggest that the majority of hypothyroid children with DS suffer from autoimmune thyroid disease.

The newborn infant must mobilize endogenous substrate stores to meet the requirements of glucose-dependent organs. High concentrations of free fatty acids and glycerol, and a rapid decrease in the respiratory quotient, indicate that lipids are an important fuel soon after birth. The purpose of the present study was to determine the onset of lipolysis and gluconeogenesis from glycerol in healthy, term, unfed infants. Eight infants were studied from a postnatal age of 3.5 +/- 0.5 h to 7.4 +/- 0.2 h using [6,6-2H2] glucose and [2-13C]glycerol analysed by gas chromatography/mass spectrometry. Plasma concentrations of glucose, glycerol and insulin averaged 2.9 +/- 0.4 mM, 369 +/- 89 microM and 9.4 +/- 9.4 +/- 3.7 microU.ml-1, respectively. The hepatic glucose production rate averaged 25.0 +/- 3.5 mumol.kg-1 min-1 (4.5 +/- 0.6 mg.kg-1.min-1) and the endogenous plasma appearance rate of glycerol 8.7 +/- 1.2 mumol.kg-1.min. On average, 57.9 +/- 8.4% of the glycerol was converted to glucose, representing 11.1 +/- 2.3% of hepatic glucose output. Thus, lipolysis and gluconeogenesis from glycerol are established within the first 8 h of life in term infants.

Growth retardation and gonadal insufficiency are well-known features of Down syndrome. In this longitudinal study, 44 home-reared children and adolescents with Down syndrome, aged 10-24 years, living in the county of Uppsala, were followed yearly. The male patients had a mean final height above that reported previously, and a close correlation between target and final heights was found. The mean final height in the female patients was below that reported earlier. Mean peak height velocities in males and females were 8.5 and 7.3 cm year-1, respectively, significantly lower than in healthy children. The mean ages at peak height velocity were 12.3 and 10.8 years, respectively, indicating early growth spurts. The serum follicle-stimulating hormone concentrations, the small testes and the negative correlation between luteinizing hormone and testicular volume in the males may indicate some primary gonadal insufficiency. For the girls, mean menarcheal age corresponded closely to that of their mothers.

The prevalence of thyroid autoantibodies, i.e. thyroglobulin antibodies and antibodies to thyroid peroxidase, was analyzed in 89 girls, aged 3-16 years (mean age 10 years), with Turner's syndrome. The analyses were performed before the start of growth-promoting treatment and during a follow-up period of 1-5 years. The patients were divided into four groups according to karyotype as follows: group 1, 45, X (n = 63); group 2 with structural abnormalities of the X chromosome (n = 10); group 3 with mosaicism but no structural abnormalities of the X chromosome (n = 10); and group 4, with isochromosome X of the long arm (n = 12): 199 healthy girls aged 12 years, served as controls. Thyroid autoantibodies were demonstrated in 46 of 89 (52%) patients with Turner's syndrome compared with 34 of 199 (17%) age-matched control girls (p < 0.001), thus confirming the relationship between thyroid abnormalities and Turner's syndrome. There was also an increase in the prevalence of thyroid antibodies with age. Simultaneous presence of both autoantibodies was significantly more frequent in group 1 (45, X) and group 4 (isochromosome X of the long arm) than in group 3 (mosaicism) (p = 0.04 and p < 0.002, respectively) and significantly more frequent in group 4 than in group 1 (p < 0.05). During 12-60 months of growth-promoting treatment, no increase in the prevalence of thyroid antibodies was observed. The findings demonstrate the importance of continuous monitoring of thyroid function in girls with Turner's syndrome.

The relationship between serum concentrations of glucose, insulin and glucagon during the first two days of life was studied in healthy newborns. The first capillary blood sample was obtained at 3-15 h of age (median 6 h; day 0) and a second sample approximately 24 h later (day 1). Serum glucose concentrations in the first sample averaged 2.1 +/- 0.07 mmol/l (mean +/- SEM; n = 60) and were positively correlated with postnatal age (p < 0.01). Serum glucagon concentrations in the first sample averaged 570 +/- 32 pg/ml and were inversely correlated with glucose concentrations (p < 0.0001). At the second sampling, serum glucose concentrations had increased to 2.9 +/- 0.07 mmol/l (p < 0.001; n = 57) and serum glucagon concentrations had decreased to 403 +/- 22 pg/ml (p < 0.001). Serum insulin concentrations were 11.7 +/- 0.3 microU/ml and 10.2 +/- 0.3 microU/ml at the two samplings and did not correlate with serum glucose concentrations. The relationship of serum glucose and hormone concentrations to maternal and infant characteristics was studied by stepwise regression analysis. Serum glucose concentration on day 0 was positively correlated with postnatal age (p < 0.01) and birth weight (p < 0.05) but inversely correlated with duration of labour (p < 0.05). Serum glucose concentration on day 1 was positively correlated with birth weight (p < 0.0001) and inversely correlated with maternal prep-pregnancy weight (p < 0.05). Similar analyses of serum hormone concentrations did not demonstrate any relationships with maternal or infant characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)