Author: "F. de Zegher" / Topic: medicine.disease - Searchworks@Jio Institute Digital Library Search Results

72 results on '"F. de Zegher"'

1. GLP-1 and IGF-I levels are elevated in late infancy in low birth weight infants, independently of GLP-1 receptor polymorphisms and neonatal nutrition

Author: Cristina Garcia-Beltran, Lourdes Ibáñez, Marta Díaz, Abel López-Bermejo, and F. de Zegher
Subjects: Adult, Male, 0301 basic medicine, endocrine system, medicine.medical_specialty, Cord, Endocrinology, Diabetes and Metabolism, Nutritional Status, Medicine (miscellaneous), Polymorphism, Single Nucleotide, Glucagon-Like Peptide-1 Receptor, Energy homeostasis, 03 medical and health sciences, Glucagon-Like Peptide 1, Diabetes mellitus, Internal medicine, medicine, Humans, Longitudinal Studies, Insulin-Like Growth Factor I, reproductive and urinary physiology, Glucagon-like peptide 1 receptor, Nutrition and Dietetics, business.industry, digestive, oral, and skin physiology, Infant, Newborn, Infant, Infant, Low Birth Weight, medicine.disease, Obesity, female genital diseases and pregnancy complications, Low birth weight, Breast Feeding, 030104 developmental biology, Endocrinology, Female, medicine.symptom, business, Weight gain, Breast feeding, hormones, hormone substitutes, and hormone antagonists
Abstract: Low birth weight followed by rapid postnatal weight gain is associated with increased risks for obesity and diabetes in adulthood. Modulation of glucagon-like-peptide 1 (GLP-1) secretion by (epi)genetic mechanisms or nutrition may influence in part this risk. Formula fed infants born small-for-gestational-age (SGA) have higher circulating GLP-1 at age 4 months than breastfed SGA or appropriate-for-gestational-age (AGA) infants. Here, we assessed GLP-1 concentrations in healthy AGA (n=149) and SGA (n=107) subjects at age 12 months, and their association with endocrine-metabolic and body composition parameters and GLP-1 receptor (GLP-1R) rs6923761 and rs3765467 polymorphisms. At birth, cord GLP-1 concentrations were comparable in AGA and SGA infants. At age 12 months, insulin-like growth factor I (IGF-I) and GLP-1 levels were higher than at birth; SGA infants displayed higher IGF-I and GLP-1 concentrations than AGA infants (both P
Published: 2017
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2. α-Defensins and bacterial/permeability-increasing protein as new markers of childhood obesity

Author: M. Planella-Colomer, Gemma Carreras-Badosa, F. de Zegher, Montserrat Gispert-Sauch, Pilar Soriano-Rodríguez, Judit Bassols, Lourdes Ibáñez, Inés Osiniri, Abel López-Bermejo, and Anna Prats-Puig
Subjects: 0301 basic medicine, medicine.medical_specialty, Longitudinal study, Nutrition and Dietetics, Waist, business.industry, Health Policy, Public Health, Environmental and Occupational Health, nutritional and metabolic diseases, medicine.disease, Obesity, Childhood obesity, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Blood pressure, Insulin resistance, Endocrinology, Intima-media thickness, 030220 oncology & carcinogenesis, Internal medicine, Pediatrics, Perinatology and Child Health, medicine, business, Body mass index
Abstract: Summary Objectives The aim of this paper is to test whether α-defensins and bacterial/permeability-increasing protein were related to obesity and cardiovascular risk factors in prepubertal children. Methods Plasma α-defensins and bacterial/permeability-increasing protein, body mass index (BMI), waist circumference, systolic blood pressure (SBP), carotid intima media thickness (cIMT), HOMA-IR and HMW-adiponectin were assessed. Results In a cross-sectional study (N = 250), higher α-defensins concentrations were positively associated with BMI, waist, SBP, cIMT, HOMA-IR and negative correlated with HMW-adiponectin (all between r = 0.191 and r = 0.377, p ≤ 0.01 and p ≤ 0.0001). Conversely, plasma bacterial/permeability-increasing protein concentrations presented inversed associated with the same parameters (all between r = −0.124 and r = −0.329; p ≤ 0.05 and p ≤ 0.0001). In a longitudinal study (N = 91), α-defensins at age 7 were associated with BMI (β = 0.189, p = 0.002; model R2 = 0.847) and waist (β = 0.241, pthinsp;= 0.001; model R2 = 0.754) at age 10. Conclusions α-Defensins and bacterial/permeability-increasing protein may be the markers of childhood obesity. Increased concentrations of α-defensins may predict BMI and abdominal fat deposition in children.
Published: 2016
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3. The macrophage activation product sCD163 is associated with a less favourable metabolic profile in prepubertal children

Author: Ferran Diaz-Roldan, Inés Osiniri, Abel López-Bermejo, Lourdes Ibáñez, Estibaliz Platero-Gutierrez, F. de Zegher, Judit Bassols, Elena Riera-Pérez, Gemma Carreras-Badosa, and Anna Prats-Puig
Subjects: 0301 basic medicine, medicine.medical_specialty, Population, 030209 endocrinology & metabolism, Overweight, Childhood obesity, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, High-density lipoprotein, Insulin resistance, Internal medicine, medicine, education, education.field_of_study, Nutrition and Dietetics, business.industry, Health Policy, Public Health, Environmental and Occupational Health, medicine.disease, Obesity, 030104 developmental biology, Endocrinology, chemistry, Pediatrics, Perinatology and Child Health, Homeostatic model assessment, medicine.symptom, business, Body mass index
Abstract: Summary Objective Macrophages are known to be involved in low-grade inflammatory processes such as obesity. soluble cluster of differentiation 163 (sCD163) is shed from the cell surface as specific macrophage activation marker. In prepubertal children, we studied if circulating sCD163 is associated with metabolic and cardiovascular risk markers. Methods A population of 236 school-aged Caucasian children (111 girls and 125 boys) aged 8 ± 1 year [81 normal weight (body mass index [BMI]-SDS
Published: 2016
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4. Uric acid, carotid intima-media thickness and body composition in prepubertal children

Author: Anna Prats-Puig, Lourdes Ibáñez, Inés Osiniri, Judit Bassols, Jose-Maria Martinez-Calcerrada, Elena Riera-Pérez, F. de Zegher, Ferran Diaz-Roldan, Abel López-Bermejo, and Gemma Carreras-Badosa
Subjects: medicine.medical_specialty, Waist, Intra-Abdominal Fat, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Asymptomatic, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Insulin resistance, Internal medicine, medicine, cardiovascular diseases, Nutrition and Dietetics, biology, business.industry, Health Policy, C-reactive protein, Public Health, Environmental and Occupational Health, nutritional and metabolic diseases, medicine.disease, Endocrinology, chemistry, Intima-media thickness, Pediatrics, Perinatology and Child Health, biology.protein, Uric acid, medicine.symptom, business, Body mass index
Abstract: Summary Background Increased uric acid is an independent biomarker for cardiovascular disease in obese adolescents and adults. Objective We investigated whether uric acid relates to carotid intima-media thickness (cIMT) in prepubertal children, and whether body mass index (BMI) and preperitoneal fat modulate this association. Methods 359 asymptomatic prepubertal Caucasian children were stratified according to BMI categories (171 with BMI-SDS 50th centile). Uric acid levels, insulin resistance (homeostasis model assessment insulin resistance; HOMA-IR), C-reactive protein (CRP), triacylglycerol (TG), systolic blood pressure (SBP), abdominal fat and cIMT (both by ultrasound) were assessed. Results Uric acid was associated with several cardiovascular risk factors, namely higher HOMA-IR, CRP, TG, BMI, waist, SBP, preperitoneal fat and cIMT (all P
Published: 2015
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5. Liver volume and hepatic adiposity in childhood: relations to body growth and visceral fat

Author: Abel López-Bermejo, Lourdes Ibáñez, J Pavia, Marta Díaz, Rita Malpique, F. de Zegher, Judit Bassols, Francesc Villarroya, and A Congo
Subjects: Male, Pediatric Obesity, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Birth weight, Medicine (miscellaneous), 030209 endocrinology & metabolism, Intra-Abdominal Fat, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Sex hormone-binding globulin, Risk Factors, Internal medicine, medicine, Humans, Longitudinal Studies, Prospective Studies, Growth Charts, Child, Prospective cohort study, Nutrition and Dietetics, biology, business.industry, Infant, Newborn, Overweight, Anthropometry, medicine.disease, Fatty Liver, Endocrinology, Liver, Infant, Small for Gestational Age, Multivariate Analysis, biology.protein, Small for gestational age, Female, 030211 gastroenterology & hepatology, Metabolic syndrome, business, Body mass index
Abstract: BACKGROUND AND OBJECTIVE: The sequence of prenatal growth restraint and postnatal catch-up growth may lead to hepato-visceral adiposity, insulin resistance and low-grade inflammation before the onset of puberty. In prepubertal children born appropriate for gestational age (AGA) or small for gestational age (SGA), we assessed potential relationships between the aforementioned sequence and liver volume. SUBJECTS/METHODS: The study population consisted of 86 children (41 AGA and 45 SGA with catch-up growth; age (mean±s.e.m.), 8.5±0.1 years), recruited into two prospective longitudinal studies. Anthropometry, endocrine-metabolic variables and inflammatory and hepatic markers were assessed, along with liver volume, hepatic adiposity and abdominal fat partitioning (by magnetic resonance imaging). RESULTS: AGA and SGA children differed in hepato-visceral adiposity, but had similar liver volumes. Boys had larger livers than girls, and higher sex hormone binding globulin and inflammation markers. Liver volume correlated with height Z-score, body mass index Z-score, HOMA-IR (homeostasis model assessment-insulin resistance) and with subcutaneous and visceral fat, but not with birth weight Z-score or with hepatic adiposity. Height, visceral fat, gender and HOMA-IR were major determinants of liver volume, together explaining 61% of its variance. CONCLUSIONS: The trajectory from prenatal restraint, via postnatal catch-up, to hepato-visceral adiposity and insulin resistance does not appear to be detectably influenced by prepubertal alterations of liver volume. Further follow-up will disclose the potential role of liver volume in the pubertal segment of this trajectory, and whether the augmented fat content and visceral adiposity in SGA subjects is followed by the development of metabolic syndrome and hepatic dysfunction in adulthood.
Published: 2018

6. Short Stature in KBG Syndrome: First Responses to Growth Hormone Treatment

Author: Lars Sävendahl, Dominique Beckers, Inge Francois, Ann Nordgren, Nele Reynaert, F. de Zegher, Kristina Casteels, Giedre Grigelioniene, Carine Carels, Koenraad Devriendt, Tjitske Kleefstra, and Charlotte W. Ockeloen
Subjects: Male, Pediatrics, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0], Growth hormone, Short stature, Endocrinology, Intellectual Disability, Intellectual disability, medicine, Humans, Abnormalities, Multiple, Craniofacial, Child, Growth Disorders, Bone Diseases, Developmental, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Human Growth Hormone, Tooth Abnormalities, business.industry, Facies, KBG SYNDROME, medicine.disease, Growth hormone treatment, Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10], Treatment Outcome, Macrodontia (tooth), Pediatrics, Perinatology and Child Health, medicine.symptom, business, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], Hormone
Abstract: Background: KBG syndrome is a rare disorder characterized by intellectual disability and associated with macrodontia of the upper central incisors, specific craniofacial findings, short stature and skeletal anomalies. Genetic corroboration of a clinical diagnosis has been possible since 2011, upon identification of heterozygous mutations in or a deletion of the ANKRD11 gene. Methods: We summarized the height data of 14 adults and 18 children (age range 2-16 years) with a genetically confirmed diagnosis of KBG syndrome. Two of these children were treated with growth hormones. Results: Stature below the 3rd centile or -1.88 standard deviation score (SDS) was observed in 72% of KBG children and in 57% of KBG adults. Height below -2.50 SDS was observed in 62% of KBG children and in 36% of KBG adults. The mean SDS of height in KBG children was -2.56 and in KBG adults -2.17. Two KBG children on growth hormone therapy increased their height by 0.6 and 1 SDS within 1 year, respectively. The former also received a gonadotropin-releasing hormone agonist due to medical necessity. Conclusion: Short stature is prevalent in KBG syndrome, and spontaneous catch-up growth beyond childhood appears limited. Growth hormone intervention in short KBG children is perceived as promising.
Published: 2015
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7. Perirenal fat is related to carotid intima-media thickness in children

Author: Elena Riera-Pérez, Judit Bassols, Inés Osiniri, Abel López-Bermejo, F. de Zegher, J-M Martínez-Calcerrada, Silvia Xargay-Torrent, Gemma Carreras-Badosa, M Feliu-Alsina, Anna Prats-Puig, Lourdes Ibáñez, and Esther Lizarraga-Mollinedo
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Abdominal Fat, Medicine (miscellaneous), Blood lipids, 030209 endocrinology & metabolism, Blood Pressure, 030204 cardiovascular system & hematology, Overweight, Asymptomatic, Gastroenterology, Carotid Intima-Media Thickness, Adipose capsule of kidney, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Risk Factors, Internal medicine, medicine, Humans, Obesity, Child, Nutrition and Dietetics, Adiponectin, business.industry, medicine.disease, Intima-media thickness, Female, medicine.symptom, business, Body mass index
Abstract: BACKGROUND/OBJECTIVES: It is well known that increased abdominal fat is associated with cardiovascular (CV) risk. Perirenal fat has been recently associated with CV risk in adults. However, studies with children are lacking. We investigated the relationship of perirenal fat and other abdominal fat depots (including preperitoneal, intra-abdominal and subcutaneous fat) with carotid intima-media thickness (cIMT-a surrogate marker of CV risk) in prepubertal children, so as to identify novel markers that can be easily assessed and used in the early prevention of cardiovascular disease. SUBJECTS/METHODS: Subjects were 702 asymptomatic prepubertal Caucasian children (418 lean, 142 overweight and 142 obese) who were recruited in a primary care setting. Ultrasound measurements (perirenal, preperitoneal, intra-abdominal and subcutaneous fat and cIMT), clinical (body mass index (BMI) and systolic blood pressure) and metabolic parameters (insulin resistance (HOMA-IR), high molecular weight (HMW) adiponectin and serum lipids) were assessed. RESULTS: Perirenal fat was associated with diverse metabolic and CV risk factors in all the studied subjects. However, in overweight and obese children, perirenal fat was mostly associated with cIMT (P
Published: 2017

8. Circulating GLP-1 in infants born small-for-gestational-age: breast-feeding versus formula-feeding

Author: Marta Díaz, Lourdes Ibáñez, Giorgia Sebastiani, Abel López-Bermejo, F. de Zegher, and Judit Bassols
Subjects: Male, medicine.medical_specialty, Diabetes risk, Endocrinology, Diabetes and Metabolism, media_common.quotation_subject, Hypothalamus, Medicine (miscellaneous), Glucagon-Like Peptide 1, Diabetes mellitus, Internal medicine, Humans, Medicine, Longitudinal Studies, Infant Nutritional Physiological Phenomena, reproductive and urinary physiology, media_common, Neuronal Plasticity, Nutrition and Dietetics, business.industry, Infant, Newborn, Infant, Appetite, medicine.disease, Infant Formula, female genital diseases and pregnancy complications, Breast Feeding, Endocrinology, Infant formula, Infant, Small for Gestational Age, Small for gestational age, Female, Adiponectin, medicine.symptom, business, Body mass index, Breast feeding, Weight gain
Abstract: Prenatal growth restraint associates with the risk for later diabetes, particularly if such restraint is followed by postnatal formula-feeding (FOF) rather than breast-feeding (BRF). Circulating incretins can influence the neonatal programming of hypothalamic setpoints for appetite and energy expenditure, and are thus candidate mediators of the long-term effects exerted by early nutrition. We have tested this concept by measuring (at birth and at age 4 months) the circulating concentrations of glucagon-like peptide-1 (GLP-1) in BRF infants born appropriate-for-gestational-age (AGA; n=63) and in small-for-gestational-age (SGA) infants receiving either BRF (n=28) or FOF (n=26). At birth, concentrations of GLP-1 were similar in AGA and SGA infants. At 4 months, pre-feeding GLP-1 concentrations were higher than at birth; SGA-BRF infants had GLP-1 concentrations similar to those in AGA-BRF infants but SGA-FOF infants had higher concentrations. In conclusion, nutrition appears to influence the circulating GLP-1 concentrations in SGA infants and may thereby modulate long-term diabetes risk.
Published: 2015
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9. Increased serum IgG and IgA in overweight children relate to a less favourable metabolic phenotype

Author: Montserrat Gispert-Sauch, Abel López-Bermejo, Ferran Diaz-Roldan, M. Crehuet-Almirall, F. de Zegher, J. Bassols, Mercè Montesinos-Costa, Anna Prats-Puig, Gemma Carreras-Badosa, and Lourdes Ibáñez
Subjects: Immunoglobulin A, medicine.medical_specialty, Nutrition and Dietetics, medicine.diagnostic_test, biology, business.industry, Health Policy, Insulin, medicine.medical_treatment, Public Health, Environmental and Occupational Health, Adipose tissue, Overweight, medicine.disease, Immunoglobulin G, Insulin resistance, Endocrinology, Internal medicine, Pediatrics, Perinatology and Child Health, Immunology, biology.protein, Medicine, medicine.symptom, business, Lipid profile, Lipoprotein
Abstract: Summary What is already known about this subject The adaptive immune system has been shown to be a novel modulator of insulin resistance. Increased activation of B lymphocytes has been described in obese mice and in obese and type 2 diabetic patients. B lymphocytes promote insulin resistance by accumulating in adipose tissue and producing pathogenic antibodies. What this study adds Increased serum concentrations of IgG and IgA were found in overweight pre-pubertal children. Increasing concentrations of IgG and IgA were in obese, but not in lean pre-pubertal children, associated with a less favourable metabolic phenotype, consisting of increased insulin resistance and a more adverse lipid profile. Background The adaptive immune system has emerged as an unexpected modulator of insulin resistance. B lymphocytes accumulate in adipose tissue and produce pathogenic antibodies that cause insulin resistance. Objective We studied whether circulating immunoglobulins (IgG, IgA and IgM) were related to metabolic risk markers in pre-pubertal children with and without overweight. Design and methods Subjects were 270 asymptomatic pre-pubertal Caucasian children (145 lean, 125 overweight) recruited in a primary care setting. Assessments included serum IgG, IgA and IgM concentrations (nephelometry), insulin resistance (HOMA-IR) and fasting lipids (triacylglycerol and high-density lipoprotein [HDL]-cholesterol). Results Overweight children had higher IgG and IgA serum levels than lean children (P ≤ 0.01). Increasing serum IgG and IgA, but not IgM, were associated with a less favourable metabolic phenotype, consisting of higher HOMA-IR and triacylglycerol and lower HDL-cholesterol, particularly in obese children, in whom serum IgG and IgA were both independently associated with HOMA-IR (β = 0.308, P = 0.017, r2 = 9.5% and β = 0.361, P = 0.005, r2 = 13.0%, respectively) and triacylglycerol (β = 0.343, P = 0.006, r2 = 11.1% and β = 0.354, P = 0.003, r2 = 12.2%, respectively). Conclusions Increased circulating IgG and IgA in overweight children are associated with a less favourable metabolic phenotype, particularly in obese children. These results suggest a relationship between adaptive immunity and insulin resistance in childhood obesity.
Published: 2013
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10. Soluble fatty acid synthase relates to bone biomarkers in prepubertal children

Author: Carmen Sitjar, Anna Prats-Puig, Abel López-Bermejo, Teresa Puig, Marta Mas-Parareda, Lourdes Ibáñez, Pilar Soriano-Rodríguez, P. Grau-Cabrera, Mercè Montesinos-Costa, J. Bassols, F. de Zegher, and Marta Díaz
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Osteocalcin, Blood lipids, Adipose tissue, Bone and Bones, Collagen Type I, Bone remodeling, Insulin resistance, N-terminal telopeptide, Internal medicine, medicine, Humans, Vitamin D, Child, Anthropometry, biology, Adiponectin, business.industry, Alkaline Phosphatase, medicine.disease, Fatty Acid Synthase, Type I, Fatty acid synthase, Endocrinology, Adipose Tissue, Solubility, biology.protein, Female, Energy Metabolism, Peptides, business, Biomarkers
Abstract: Circulating soluble fatty acid synthase (FASN, a key enzyme in de novo biosynthesis of fatty acids, expressed in both adipocytes and osteoblasts) is clinically related to a less favorable bone profile in healthy prepubertal children. Soluble FASN may participate in the reciprocal regulation between fat and bone metabolism. Fatty acid synthase (FASN), a key enzyme in de novo biosynthesis of fatty acids, is expressed in adipocytes and osteoblasts. We hypothesized that FASN may participate in the crosstalk between fat and bone. To this aim, we studied the relation between circulating soluble FASN (an extracellular FASN that reflects previously intracellular enzymatic activity) and adipose tissue and bone biomarkers in prepubertal children. Circulating soluble FASN, total and high molecular weight (HMW) adiponectin, bone biomarkers [osteocalcin (OC), uncarboxylated osteocalcin (ucOC), C-terminal cross-linked telopeptide of type I collagen (CTX), bone-specific alkaline phosphatase (BSAP)], and a profile of energy metabolism [body fat, insulin resistance and secretion (HOMA), serum lipids] were assessed in 84 asymptomatic prepubertal children (44 girls, 40 boys, age 6.8 ± 0.1 year). Serum 25-OH Vitamin D (Vit D) was additionally measured. Circulating soluble FASN increased with increasing HMW adiponectin (r = 0.29, p = 0.01) and decreasing serum Vit D (r = −0.21, p < 0.05), and was related to a less favorable bone profile, showing negative associations with bone-derived metabolic parameters [total OC (r = −0.33, p = 0.002) and ucOC (r = −0.37, p < 0.0001)] and a positive association with the CTX-to-BSAP ratio (r = 0.31, p < 0.01). These correlations were not explained by age, gender, body fat, insulin resistance or secretion or serum lipids; however, they were predominant in those subjects with Vit D levels below the population median. Circulating soluble FASN relates to both adipose tissue and bone biomarkers in prepubertal children, with associations that are dependent on Vit D concentrations. These findings suggest that FASN may participate in the crosstalk between fat and bone metabolism.
Published: 2011
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11. The sequence of prenatal growth restraint and postnatal catch-up growth: normal heart but thicker intima-media and more pre-peritoneal fat in late infancy

Author: Lourdes Ibáñez, Abel López-Bermejo, F Rosés, F. de Zegher, J S de Toledo, S Pie, Cristina Garcia-Beltran, Giorgia Sebastiani, and A Guerra
Subjects: 0301 basic medicine, Body height, medicine.medical_treatment, Physiology, 030209 endocrinology & metabolism, Fasting glucose, 03 medical and health sciences, 0302 clinical medicine, medicine, Abdominal fat, reproductive and urinary physiology, Normal heart, 030109 nutrition & dietetics, Nutrition and Dietetics, Adiponectin, business.industry, Health Policy, Insulin, Public Health, Environmental and Occupational Health, medicine.disease, Obesity, female genital diseases and pregnancy complications, Pediatrics, Perinatology and Child Health, cardiovascular system, Small for gestational age, business
Abstract: BACKGROUND The sequence of prenatal growth restraint and postnatal catch-up growth leads to a thicker intima-media and more pre-peritoneal fat by age 3-6 years. OBJECTIVES To study whether carotid intima-media thickness (cIMT) and pre-peritoneal fat differ already between catch-up small-for-gestational-age (SGA) infants and appropriate-for-gestational-age (AGA) controls in late infancy (ages 1 and 2 years) and whether such differences - if any - are accompanied by differences in cardiac morphology and function. METHODS Longitudinal assessments included body height and weight; fasting glucose, insulin, Insulin-like growth factor (IGF-I), high-molecular-weight adiponectin; body composition (by absorptiometry); cIMT, aortic IMT, pre-peritoneal fat partitioning (by ultrasound); cardiac morphometry and function (by echocardiography) in AGA and SGA infants at birth, at age 1 year (N = 87), and again at age 2 years (N = 68). RESULTS Catch-up SGA infants had already a thicker cIMT than AGA controls at ages 1 and 2 years, and more pre-peritoneal fat by age 2 years (all p values between
Published: 2018
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12. Growth Hormone Therapy in Short Children Born Small for Gestational Age

Author: F. de Zegher, David B. Dunger, Lourdes Ibáñez, and Ken K. Ong
Subjects: Pediatrics, medicine.medical_specialty, Body height, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Growth hormone, Child Development, Endocrinology, medicine, Humans, Glucose homeostasis, Insulin-Like Growth Factor I, Child, business.industry, Insulin, Infant, Newborn, medicine.disease, Child development, Body Height, Blood pressure, Child, Preschool, Growth Hormone, Infant, Small for Gestational Age, Pediatrics, Perinatology and Child Health, Gh treatment, Small for gestational age, business
Abstract: There is still a lack of data from randomized, controlled, long-term studies of growth hormone (GH) treatment in children born small for gestational age (SGA), but the available evidence indicates consistently that GH therapy is a valid growth-promoting treatment in these children, particularly if started early. Whilst side effects appear uncommon, ongoing surveillance is required and treated children should be monitored for changes in glucose homeostasis, lipid profiles and blood pressure, especially during puberty. We provide an update on the safety and efficacy of GH treatment in short children born SGA.
Published: 2006
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13. Puberty after Prenatal Growth Restraint

Author: Lourdes Ibáñez and F. de Zegher
Subjects: Male, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, media_common.quotation_subject, Puberty, Precocious, Physiology, Pubarche, Fetal Development, Endocrinology, Insulin resistance, Pregnancy, Internal medicine, medicine, Humans, Precocious puberty, Ovulation, reproductive and urinary physiology, media_common, Fetal Growth Retardation, business.industry, Adrenarche, Puberty, Infant, Newborn, medicine.disease, Body Height, female genital diseases and pregnancy complications, Infant, Small for Gestational Age, Pediatrics, Perinatology and Child Health, Menarche, Small for gestational age, Female, business
Abstract: There is increasing evidence for a link between prenatal growth and pubertal development. Here we highlight a selection of pubertal characteristics in children who were born small for gestational age (SGA). Boys born SGA are at risk of high levels of follicle-stimulating hormone (FSH) and low levels of inhibin B and a small testicular volume during adolescence. In girls born SGA, the age at pubertal onset and the age at menarche are advanced by about 5–10 months; prenatal growth restraint may also be associated with higher FSH levels and smaller internal genitalia in adolescence. The ovulation rate was found to be reduced in adolescent girls born SGA, and an insulin-sensitizing therapy was capable of raising this low ovulation rate. Menarche is definitely advanced in girls born SGA with precocious pubarche and in those with an early-normal onset of puberty. Current evidence suggests that insulin resistance is a key mechanism linking a post-SGA state to early menarche; hence, insulin sensitization may become a valid approach to prevent early menarche and early growth arrest in girls born SGA.
Published: 2006
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14. Absence of hepatotoxicity after long-term, low-dose flutamide in hyperandrogenic girls and young women

Author: F. de Zegher, Lourdes Ibáñez, Angela Ferrer, and Adriana Jaramillo
Subjects: Adult, medicine.medical_specialty, Adolescent, Side effect, medicine.drug_class, medicine.medical_treatment, Physiology, Gestodene, Antiandrogen, Drug Administration Schedule, Transaminase, Flutamide, chemistry.chemical_compound, Internal medicine, Humans, Medicine, Aspartate Aminotransferases, Child, biology, business.industry, Insulin, Rehabilitation, Hyperandrogenism, Obstetrics and Gynecology, Alanine Transaminase, Androgen Antagonists, Drospirenone, General Medicine, medicine.disease, Obesity, Polycystic ovary, Metformin, Endocrinology, Liver, Reproductive Medicine, Alanine transaminase, El Niño, chemistry, Toxicity, biology.protein, Female, business, Biomarkers, Polycystic Ovary Syndrome, medicine.drug
Abstract: Flutamide is a nonsteroidal antiandrogenic agent that to date has been used chiefly in treating prostate cancer. Hepatotoxicity, although rare, is a potentially fatal side effect that has been documented with doses of 750 to 1500 mg daily. Minor hepatotoxicity has been associated with doses as low as 250 mg daily. This study examined the risk of hepatotoxicity when flutamide was given in ultralow doses for up to 3 years and for periods as long as 54 months. Participants were 190 hyperandrogenic girls and young women, 150 of whom had established and 40 incipient polycystic ovary syndrome (PCOS); none were obese. Flutamide was given alone or in combination with metformin, an insulin sensitizer, and/or an estro-progestagen oral contraceptive containing gestodene or drospirenone. Doses of flutamide ranged from 62.5 to 250 mg daily. Circulating levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) served as markers of hepatic toxicity. All participants had normal levels of ALT and AST at baseline, and concentrations were unchanged during flutamide treatment-both 3 months after the start of treatment and at the last assessment, which took place after a mean of 19 months on treatment. Treatment times ranged up to 54 months. No subject had an AST or ALT level of 45 U/L or higher at any time. These findings suggest that flutamide is a safe treatment when used in low dosage to treat hyperandrogenic, nonobese girls and young women having actual or impending PCOS. It remains possible that hepatic toxicity may, in rare instances, develop in patients taking ultralow doses of flutamide. Nevertheless, the investigators anticipate that such doses may become a part of treating hyperandrogenic girls and young women with PCOS. They do recommend that transaminase levels be monitored during flutamide treatment.
Published: 2005
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15. Markers for cardiovascular disease in monozygotic twins discordant for the use of third-generation oral contraceptives

Author: Robert Vlietinck, Gaston Beunen, Catherine Derom, F. de Zegher, Johan Verhaeghe, Robert Fagard, Chantal Mathieu, Ruth J. F. Loos, Populatie Genetica, RS: NUTRIM School of Nutrition and Translational Research in Metabolism, and RS: CARIM School for Cardiovascular Diseases
Subjects: Adult, Blood Glucose, medicine.medical_specialty, Ambulatory blood pressure, Hydrocortisone, medicine.medical_treatment, Monozygotic twin, Blood Pressure, chemistry.chemical_compound, Insulin resistance, Internal medicine, Internal Medicine, medicine, Diseases in Twins, Humans, Insulin, Proinsulin, medicine.diagnostic_test, Triglyceride, business.industry, Research Support, Non-U.S. Gov't, Twins, Monozygotic, Blood Pressure Monitoring, Ambulatory, medicine.disease, Lipids, Insulin-Like Growth Factor Binding Protein 1, Contraceptives, Oral, Combined, Endocrinology, Blood pressure, chemistry, Cardiovascular Diseases, Biological Markers, Female, Insulin Resistance, Progestins, Lipid profile, business, Biomarkers
Abstract: Markers for cardiovascular disease in monozygotic twins discordant for the use of third-generation oral contraceptives.Loos RJ, Verhaeghe J, De Zegher F, Beunen G, Derom C, Fagard R, Mathieu C, Vlietinck R.Department of Sport and Movement Sciences, Faculty of Physical Education and Physiotherapy, Katholieke Universiteit Leuven, 3000 Leuven, Belgium. loosr@pbrc.eduOral contraceptives (OC) modulate the risk for developing cardiovascular (CV) diseases. The aim of this study was to determine whether the use of third-generation OC has an impact on markers of CV disease in genetically identical women. We performed an intrapair comparison in 27 monozygotic twin pairs, one of whom was taking third-generation OC, whereas the other was not using OC. Biometric parameters were ascertained and conventional and 24-h ambulatory blood pressure (BP) was recorded. A fasting blood sample was taken for the measurement of glucose, insulin, proinsulin, lipids, and insulin-like growth factor binding protein-1 (IGFBP-1). Insulin resistance and beta-cell function were calculated by homeostasis model assessment (HOMA). A 24-h urine sample for cortisol was obtained. Third-generation OC use increased 24-h ambulatory systolic and diastolic BP by 5.2 and 3.9 mmHg, respectively (both P=0.0003). There was no effect on glucose, insulin and proinsulin levels, and on HOMA parameters, but the IGFBP-1 levels were markedly raised (P=0.0009). The lipid profile showed a 34% increase in triglyceride levels (P < 0.0001), but also a 7% increase in HDL-cholesterol levels (P=0.037). Use of third-generation OC impacts on CV disease markers in young-adult genetically identical women. Some changes are beneficial (increased HDL-cholesterol), whereas others may be deleterious (increased BP and triglyceride levels) or have unknown effects at this time (increased IGFBP-1 levels).
Published: 2003

16. The sequence of prenatal growth restraint and post-natal catch-up growth leads to a thicker intima-media and more pre-peritoneal and hepatic fat by age 3-6 years

Author: F. de Zegher, Judit Bassols, Giorgia Sebastiani, Marta Díaz, Gemma Aragonès, Abel López-Bermejo, and Lourdes Ibáñez
Subjects: Blood Glucose, Male, Pediatric Obesity, medicine.medical_treatment, Overweight, Weight Gain, Gastroenterology, Carotid Intima-Media Thickness, Body Mass Index, 0302 clinical medicine, Child Development, Insulin-Like Growth Factor I, Child, reproductive and urinary physiology, Nutrition and Dietetics, medicine.diagnostic_test, Health Policy, female genital diseases and pregnancy complications, Child, Preschool, Obesity, Abdominal, Infant, Small for Gestational Age, cardiovascular system, Female, Adiponectin, medicine.symptom, medicine.medical_specialty, Abdominal Fat, 030209 endocrinology & metabolism, 03 medical and health sciences, Insulin resistance, 030225 pediatrics, Internal medicine, medicine, Humans, business.industry, Insulin, Public Health, Environmental and Occupational Health, Infant, Newborn, Infant, Magnetic resonance imaging, medicine.disease, Endocrinology, Cross-Sectional Studies, Intima-media thickness, Pediatrics, Perinatology and Child Health, Insulin Resistance, business, Body mass index, Weight gain, Biomarkers
Abstract: SummaryBackground Infants born small-for-gestational-age (SGA) who develop post-natal weight catch-up are at risk for insulin resistance, central adiposity and cardiovascular disease in later life, even in the absence of overweight. Objective In young (age 3–6 years) non-obese SGA children, we assessed arterial health (as judged by intima-media thickness [IMT]) and abdominal fat distribution (subcutaneous, visceral, preperitoneal and hepatic components by magnetic resonance imaging [MRI] and/or ultrasound [US]) besides a selection of endocrine markers. Methods Comparisons of measures in SGA (n = 27) vs. appropriate-for-GA (AGA) children (n = 19) of similar height, weight and body mass index. Longitudinal outcomes (age 3–6 years) were carotid IMT (cIMT); fasting glucose, circulating insulin, IGF-I and high-molecular-weight (HMW) adiponectin; abdominal fat partitioning by US. Cross-sectional outcomes (age 6 years) were aortic IMT (aIMT) and abdominal fat partitioning by MRI. Results At 3 and 6 years, cIMT and IGF-I results were higher and HMW adiponectin lower in SGA than AGA children; at 6 years, SGA subjects had also a thicker aIMT and more pre-peritoneal and hepatic fat, and were less insulin sensitive (all P values between
Published: 2015

17. Circulating FGF19 and FGF21 surge in early infancy from infra- to supra-adult concentrations

Author: Marta Díaz, Giorgia Sebastiani, José M. Gallego-Escuredo, Pere Domingo, Francesc Villarroya, Gemma Aragonès, F. de Zegher, Abel López-Bermejo, Lourdes Ibáñez, and David Sánchez-Infantes
Subjects: Adult, Male, endocrine system, medicine.medical_specialty, FGF21, genetic structures, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), Insulin resistance, Internal medicine, Diabetes mellitus, Medicine, Humans, Obesity, Receptor, Nutrition and Dietetics, business.industry, Adipose tissue metabolism, Infant, Newborn, Infant, FGF19, Early infancy, medicine.disease, Receptors, Fibroblast Growth Factor, body regions, Fibroblast Growth Factors, surgical procedures, operative, Endocrinology, Adipose Tissue, Diabetes Mellitus, Type 2, Body Composition, Female, Signal transduction, Insulin Resistance, business, hormones, hormone substitutes, and hormone antagonists, Signal Transduction
Abstract: BACKGROUND/OBJECTIVE: Fibroblast growth factor 19 (FGF19) and 21 (FGF21) have been linked to obesity and type 2 diabetes in adults. We assessed the circulating concentrations of these factors in human neonates and infants, and their association with the endocrine-metabolic changes associated to prenatal growth restraint. SUBJECTS/METHODS: Circulating FGF19 and FGF21, selected hormones (insulin, insulin-like growth factor I and high- molecular-weight (HMW) adiponectin) and body composition (absorptiometry) were assessed longitudinally in 44 infants born appropriate( AGA) or small-for-gestational-age (SGA). Measurements were performed at 0, 4 and 12 months in AGA infants; at 0 and 4 months in SGA infants; and cross-sectionally in 11 first-week AGA newborns. RESULTS: Circulating FGF19 and FGF21 surged >10-fold in early infancy from infra- to supra-adult concentrations, the FGF19 surge appearing slower and more pronounced than the FGF21 surge. Whereas the FGF21 surge was of similar magnitude in AGA and SGA infants, FGF19 induction was significantly reduced in SGA infants. In AGA and SGA infants, cord-blood FGF21 and serum FGF19 at 4 months showed a positive correlation with HMW adiponectin (r = 0.49, P = 0.013; r = 0.43, P = 0.019, respectively). CONCLUSIONS: Our results suggest that these early FGF19 and FGF21 surges are of a physiological relevance that warrants further delineation and that may extend beyond infancy.
Published: 2014

18. Precocious Pubarche, Hyperinsulinism, and Ovarian Hyperandrogenism in Girls: Relation to Reduced Fetal Growth

Author: Neus Potau, Inge Francois, F. de Zegher, and Lourdes Ibáñez
Subjects: medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, Birth weight, Clinical Biochemistry, Puberty, Precocious, Biochemistry, Endocrinology, Insulin resistance, Hyperinsulinism, Internal medicine, Fetal growth, medicine, Hyperinsulinemia, Birth Weight, Humans, Insulin, Precocious puberty, Ovarian Diseases, Child, Fetal Growth Retardation, Ovarian Hyperandrogenism, business.industry, Adrenarche, Biochemistry (medical), Hyperandrogenism, Obstetrics and Gynecology, General Medicine, medicine.disease, Precocious pubarche, Low birth weight, Child, Preschool, Female, medicine.symptom, business
Abstract: Pronounced adrenarche with precocious pubarche (PP) in girls has been associated with hyperinsulinism and subsequent functional ovarian hyperandrogenism (FOH). Recently, pronounced adrenarche and insulin resistance have each been related to low birth weight. We have now tested the hypothesis that the frequent concurrence of PP with pronounced adrenarche, FOH, and hyperinsulinemia in girls may be secondary to separate relationships between these conditions and low birth weight. A total of 185 girls (aged 5-18 yr) without endocrinopathy or with PP and pronounced adrenarche with or without FOH were studied; mean serum insulin (MSI) concentrations were determined after a standardized oral glucose tolerance test. Birth weight SD scores [mean (SEM)] of control girls (0.38+/-0.08; n = 83) were higher (P < 0.0001) than those of PP girls (-0.81+/-0.13; n = 102). Among postmenarcheal PP girls, birth weight SD scores of girls without FOH (-0.25+/-0.19; n = 25) were higher (P < 0.0001) than those in girls with FOH (-1.51+/-0.28; n = 23). In pubertal girls (n = 145), MSI levels correlated negatively with birth weight SD scores (r = -0.48; P < 0.05), independently of PP. MSI levels in girls with birth weight below 1 SD (93+/-9 mU/L; n = 33) were higher (P < 0.0001) than those in girls with birth weight between -1 and +1 SD (52+/-2 mU/L; n = 94), whereas glycemia profiles were comparable. Integration of the aforementioned data suggests that there may be a sequence in the associations between reduced fetal growth and components of the postnatal endocrine system; minor fetal growth reduction appears to be associated with amplified adrenarche, whereas more pronounced prenatal growth restriction seem to precede FOH and hyperinsulinemia during adolescence. In conclusion, these findings corroborate the hypothesis that the frequent concurrence of PP (with pronounced adrenarche), FOH, and hyperinsulinemia in girls may result from a common early origin (low birth weight serving as a marker), rather than from a direct interrelationship later in life.
Published: 1998
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19. Short stature of prenatal origin: craniofacial growth and dental maturation

Author: R. Van Erum, F. de Zegher, Carine Carels, and Michiel Mulier
Subjects: Adult, Male, Adolescent, Cephalometry, Dentistry, Orthodontics, Short stature, Sex Factors, medicine, Dentition, Humans, Craniofacial, Child, Maxillofacial Development, Craniofacial growth, Growth Disorders, Human Growth Hormone, business.industry, Infant, Newborn, Mandible, Bone age, Reference Standards, Craniometry, medicine.disease, Child, Preschool, Infant, Small for Gestational Age, Linear Models, Small for gestational age, Female, medicine.symptom, business
Abstract: SUMMARY Recently, children born small for gestational age (SGA) with a catch-up growth failure, have been selected for high dose growth hormone (GH) treatment. In order to gain greater insight concerning dentofacial growth and maturation of these patients, and to evalu ate the possible effects of high dose GH administration on facial structures, craniofacial growth and dental maturation were evaluated in short SGA persons. Seventy-seven cephalo grams and orthopantomograms were available from 48 subjects, aged between 2 and 32 years. Craniofacial growth was assessed by calculating age- and gender-specific standard devi ation scores (SOS) for eight linear and five angular measurements. Tooth formation was evaluated by means of a dental delay score (i.e. dental age minus chronological age). The SOS for craniofacial growth measurements for the lateral aspect showed a short anterior cranial base (-1.8 SOS), a small retropositioned mandible (~-1.7 SOS) and a small maxilla (-1.5 SOS); a high mandibular plane angle (+ 1.9 SOS) and a wide cranial base angle 1+1 SOS). These findings result in a small retrognathic face with a relatively increased lower anterior face height (+ 1.7 SOS). In contrast to skeletal maturation, dental age was not delayed. The general growth retardation is, apparently, reflected to a differential extent within the craniofacial complex, while dental maturation appears to be a distinct process tightly linked to chronological age, and independent of general growth and bone age.
Published: 1998
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20. Growth hormone treatment of short children born small for gestational age: reappraisal of the rate of bone maturation over 2 years and metanalysis of height gain over 4 years

Author: O. Butenandt, B Jonsson, F. de Zegher, A Löfström, K Albertsson-Wikland, J L Chaussain, and P Chatelain
Subjects: medicine.medical_specialty, Bone Development, Human Growth Hormone, business.industry, Bone age, General Medicine, Growth hormone, medicine.disease, Short stature, Body Height, Growth hormone treatment, Regimen, Endocrinology, Child, Preschool, Internal medicine, Infant, Small for Gestational Age, Pediatrics, Perinatology and Child Health, medicine, Bone maturation, Humans, Small for gestational age, medicine.symptom, business, Linear growth
Abstract: A minority of children born small for gestational age (SGA) fail to achieve sufficient catch-up growth during infancy and remain short throughout childhood, apparently without being growth hormone (GH) deficient. A previous metanalysis of four trials revealed that GH treatment over a period of 2 years induced a dose-dependent acceleration of linear growth and, to a lesser extent, of the rate of bone maturation in short, prepubertal children born SGA. The rate of bone maturation and the change in height SDS for bone age from the previous 2-year metanalysis have been re-analysed according to chronological age (two prepubertal age groups: group A, 3.0-5.9 years old; group B, 6.0-8.9 years old). The rate of bone maturation was slower in younger than in older prepubertal children; this difference was more marked in children receiving high-dose (0.2 or 0.3 IU/kg/day) GH treatment (p < or = 0.01). Accordingly, the change in height SDS for bone age was increased by high-dose GH treatment in both age groups (p < or = 0.01), and was more pronounced in younger than in older children (1.45 +/- 0.28 versus 0.63 +/- 0.20; p < or = 0.01). Height SDS data from 100 short, prepubertal children born SGA have been analysed over 4 years. The change in height SDS appeared to be related to the average dose of GH. A mean GH dose of 0.1 IU/kg/day over 4 years was administered either as 0.1 IU/kg/day for 4 years (continuous) or as 0.2 IU/kg/day for 2 years, followed by 2 years without GH treatment (discontinuous). After 4 years of treatment, the increase in height SDS for the continuous and discontinuous treatment schedules was similar, being 1.42 +/- 0.10 SDS and 1.58 +/- 0.17 SDS, respectively. In a second regimen, a mean GH dose of 0.2 IU/kg/day over 3 years was administered either as 0.2 IU/kg/day for 3 years (continuous) or as 0.3 IU/kg/day for 2 years, followed by 1 year without GH treatment (discontinuous). After 3 years, the increase in height SDS with the continuous and discontinuous treatment schedules was similar, being 2.01 +/- 0.18 SDS and 2.22 +/- 0.16 SDS, respectively. GH administration was well tolerated in all treatment groups. In conclusion, the rate of bone maturation in short, prepubertal children born SGA treated with GH appeared to depend not only on the dose of GH, but also on the age of the child. GH treatment resulted in a prolonged increase in height SDS, the magnitude of the rise being dependent on the average GH dose rather than on the continuous or discontinuous mode of GH administration.
Published: 1997
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21. High-dose growth hormone treatment of short children born small for gestational age

Author: P. Jönsson, Annika Löfström, R. G. Rosenfeld, G. Thiry, Claudine Heinrichs, P. Malvaux, M. Maes, S. E. Gargosky, L. Breysem, M. V. L. du Caju, Jean-Pierre Bourguignon, J De Schepper, M. Craen, and F. de Zegher
Subjects: medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Osteocalcin, Clinical Biochemistry, Weight Gain, Biochemistry, Short stature, Endocrinology, Insulin-Like Growth Factor II, Age Determination by Skeleton, Internal medicine, medicine, Humans, Insulin, Insulin-Like Growth Factor I, Growth Disorders, biology, business.industry, Biochemistry (medical), Infant, Newborn, Bone age, medicine.disease, Body Height, Growth hormone treatment, Insulin-Like Growth Factor Binding Protein 3, Child, Preschool, Growth Hormone, Infant, Small for Gestational Age, biology.protein, Bone maturation, Small for gestational age, Human medicine, medicine.symptom, business, Body mass index, Weight gain
Abstract: The effect of GH administration was evaluated over 2 yr in 50 short, prepubertal, non-GH deficient children born small for gestational age, who had been randomly allocated to a group receiving no treatment or daily sc GH treatment at a dose of 0.2 or 0.3 IU/kg. At the start of the study, mean age was 5.2 yr, bone age was 4.0 yr, height sos was -3.5, height velocity sos was -0.8, weight SDS was -2.7, and body mass index SDS was -1.9. Catch-up growth was observed in none of the untreated and all of the treated children. The response to GH treatment included a near doubling of growth velocity and of weight gain and a mean height increment of more than 2 SDS. GH treatment was associated with a distinct acceleration of bone maturation. The differences between the growth responses evoked by the two GH doses were minor. The prepubertal GH-induced catch-up growth was associated with elevated serum concentrations of insulin, insulin-like growth factor-I, insulin-like growth factor binding protein-3, and osteocalcin, whereas insulin-like growth factor-II levels remained unaltered. GH treatment was well tolerated. In conclusion, high-dose GH administration over 2 yr is emerging as a potential therapy to increase the short stature that results from insufficient catch-up growth in young children born small for gestational age. The long-term impact of this approach remains to be delineated.
Published: 1996
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22. Paucity of intrahepatic bile ducts, solitary kidney and atrophic pancreas with diabetes mellitus: Atypical Alagille syndrome?

Author: K. Devriendt, L. Dooms, W. Proesmans, F. de Zegher, E. Eggermont, and V. Desmet
Subjects: Male, Autoimmune disease, Kidney, Pathology, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Biopsy, Intrahepatic bile ducts, medicine.disease, Alagille Syndrome, Diabetes Mellitus, Type 1, medicine.anatomical_structure, Liver, Dysplasia, Child, Preschool, Diabetes mellitus, Pediatrics, Perinatology and Child Health, Alagille syndrome, medicine, Humans, business, Pancreas
Abstract: A child with the tentative diagnosis of Alagille syndrome is reported. Additional renal abnormalities are unilateral kidney agenesis and a kidney with subcortical cysts with decreased function. At the age of 5 years, insulin-dependent diabetes mellitus developed, with the pancreas being atrophic and negative pancreatic islet cell antibodies. This observation extends the picture of Alagille syndrome and suggests an overlap with renal-hepatic-pancreatic dysplasia (Iyemark syndrome).
Published: 1996
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23. ARX mutation in a boy with transsphenoidal encephalocele and hypopituitarism

Author: H Van Esch, Jamel Chelly, F. de Zegher, K Devriendt, Karine Poirier, T Bienvenu, J-P Fryns, and Maureen Holvoet
Subjects: medicine.medical_specialty, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, Hypopituitarism, medicine.disease, Bioinformatics, Encephalocele, Endocrinology, Text mining, Internal medicine, Mutation (genetic algorithm), Genetics, Medicine, business, Genetics (clinical)
Published: 2004
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24. Insulin-like growth factors and their binding proteins in the term and preterm human fetus and neonate with normal and extremes of intrauterine growth

Author: Ron G. Rosenfeld, Sharron E. Gargosky, B A Dsupin, Linda C. Giudice, R. A. Crystal, Raymond L. Hintz, L. de las Fuentes, and F. de Zegher
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Birth weight, Clinical Biochemistry, Biochemistry, Embryonic and Fetal Development, Endocrinology, Pregnancy, Reference Values, Somatomedins, Internal medicine, medicine, Humans, Fetus, Fetal Growth Retardation, Labor, Obstetric, biology, Insulin, Biochemistry (medical), Infant, Newborn, Proteolytic enzymes, Gestational age, medicine.disease, Insulin-Like Growth Factor Binding Proteins, Insulin-like growth factor 2, biology.protein, Gestation, Female, lipids (amino acids, peptides, and proteins), Carrier Proteins, Infant, Premature, hormones, hormone substitutes, and hormone antagonists
Abstract: Insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs), and insulin are believed to be important in the regulation of fetal and neonatal growth. We previously reported that the profiles of IGFBPs in fetal cord serum (FCS) were dependent on the growth/metabolic status of the fetus. The goals of the current study were to examine the IGF system in FCS from term fetuses with normal growth, those with intrauterine growth retardation (IUGR), and those who were large for gestational age (LGA) and in FCS from normal weight preterm (25-37 weeks) and term fetuses in the neonatal period from the day of birth (day 0) until 7 days of age (day 7). Western ligand blotting (WLB) of term FCS revealed IGFBPs with mol wt of 43 and 38 kilodaltons (kDa; IGFBP-3), 34 kDa (IGFBP-2), 28 kDa (IGFBP-1 and glycosylated IGFBP-4), and 24 kDa (IGFBP-4). In IUGR FCS, there was a 50% decrease in IGFBP-3 detected by WLB, which was shown not to be due to an IGFBP-3 protease in IUGR sera. In LGA FCS, IGFBP-3 levels were elevated 2-fold by densitometric analysis of ligand blots. In normal term FCS, the following levels (+/- SE) were present: IGF-I, 76 +/- 16; IGF-II, 401 +/- 38; IGFBP-3, 700 +/- 112; IGFBP-1, 77 +/- 10 ng/mL; and insulin, 3.8 +/- 1.6 microU/mL. In IUGR FCS, IGF-I, IGF-II, and IGFBP-3 were significantly reduced, and IGFBP-1 was 7-fold higher than in FCS from normal weight fetuses. In LGA FCS, IGF-I, insulin, and IGFBP-3 were significantly increased, whereas IGFBP-1 was significantly decreased. During the neonatal period, IGF-I levels on day 0 were 4-fold higher in FCS from term (38-40 weeks) compared to preterm (25-31 weeks) newborns. FCS IGF-II levels did not change significantly on day 0 between 25-40 weeks gestation. In the first 7 days of postnatal life, IGF-I levels were unchanged in preterm newborns, whereas in term neonates, IGF-I levels decreased precipitously on day 1, remained low during the first 3 days of life, and returned to birth levels by the end of the first week. In contrast, IGF-II and IGFBP-3 levels did not significantly change during the first week of life in preterm or term newborns.(ABSTRACT TRUNCATED AT 400 WORDS)
Published: 1995
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25. Validation of the continuous glucose monitoring sensor in preterm infants

Author: M VanWeissenbruch, K Beardsall, Marta Thio, Isabel Iglesias, F. de Zegher, David B. Dunger, M de Jong, Christine Vanhole, Sophie Vanhaesebrouck, Amanda Ogilvy-Stuart, Luc Cornette, Paula Midgley, Christopher R. Palmer, Iviano Ossuetta, Bryan Gill, Pediatric surgery, and ICaR - Circulation and metabolism
Subjects: Blood Glucose, Male, Pediatrics, medicine.medical_specialty, Point-of-Care Systems, Infant, Premature, Diseases, Sensitivity and Specificity, law.invention, Randomized controlled trial, law, Diabetes mellitus, Intensive care, medicine, Humans, Infant, Very Low Birth Weight, Clinical significance, Prospective Studies, Bland–Altman plot, Prospective cohort study, Point of care, Monitoring, Physiologic, business.industry, Infant, Newborn, Obstetrics and Gynecology, Reproducibility of Results, General Medicine, medicine.disease, Hypoglycemia, Low birth weight, Hyperglycemia, Pediatrics, Perinatology and Child Health, Intensive Care, Neonatal, Female, medicine.symptom, business, Infant, Premature
Abstract: Objective Recent studies have highlighted the need for improved methods of monitoring glucose control in intensive care to reduce hyperglycaemia, without increasing the risk of hypoglycaemia. Continuous glucose monitoring is increasingly used in children with diabetes, but there are little data regarding its use in the preterm infant, particularly at extremes of glucose levels and over prolonged periods. This study aimed to assess the accuracy of the continuous glucose monitoring sensor (CGMS) across the glucose profile, and to determine whether there was any deterioration over a 7 day period. Design Prospectively collected CGMS data from the NIRTURE Trial was compared with the data obtained simultaneously using point of care glucose monitors. Setting An international multicentre randomised controlled trial. Patients One hundred and eighty-eight very low birth weight control infants. Outcome measures Optimal accuracy, performance goals (American Diabetes Association consensus), Bland Altman, Error Grid analyses and accuracy. Results The mean (SD) duration of CGMS recordings was 156.18 (29) h (6.5 days), with a total of 5207 paired glucose levels. CGMS data correlated well with point of care devices (r=0.94), with minimal bias. It met the Clarke Error Grid and Consensus Grid criteria for clinical significance. Accuracy of single readings to detect set thresholds of hypoglycaemia, or hyperglycaemia was poor. There was no deterioration over time from insertion. Conclusions CGMS can provide information on trends in glucose control, and guidance on the need for blood glucose assessment. This highlights the potential use of CGMS in optimising glucose control in preterm infants.
Published: 2012
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26. Variations in the obesity genes FTO, TMEM18 and NRXN3 influence the vulnerability of children to weight gain induced by short sleep duration

Author: E Fortea, Anna Prats-Puig, Elena Riera-Pérez, R Cortés-Marina, P. Grau-Cabrera, Pilar Soriano-Rodríguez, F. de Zegher, Abel López-Bermejo, Lourdes Ibáñez, and J. Bassols
Subjects: Male, Sleep Wake Disorders, medicine.medical_specialty, Waist, Genotype, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Nerve Tissue Proteins, Intra-Abdominal Fat, Weight Gain, Asymptomatic, Polymorphism, Single Nucleotide, Body Mass Index, Insulin resistance, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Obesity, Child, Nutrition and Dietetics, business.industry, nutritional and metabolic diseases, Membrane Proteins, Proteins, medicine.disease, Confidence interval, Sleep deprivation, Endocrinology, Child, Preschool, Female, medicine.symptom, Insulin Resistance, Waist Circumference, business, Body mass index, Weight gain
Abstract: Shorter sleep duration predisposes to obesity, but the mechanisms whereby sleep deprivation affects body weight are poorly understood. We tested whether this association is modulated by the obesity genes FTO, TMEM18 and NRXN3. Body mass index (BMI), waist circumference, visceral fat (abdominal ultrasound), homeostasis model assessment for insulin resistance (HOMA-IR), systolic blood pressure (SBP) and sleep time per 24 h were assessed in 297 asymptomatic children (151 boys, 146 girls; age range 5–9 years; BMI s.d. score range −2.0–4.0). Associations between sleep duration and the abovementioned outcomes were tested for three common single-nucleotide polymorphisms (SNPs), namely FTO (rs9939609), TMEM 18 (rs4854344) and NRXN3 (rs10146997), as well as for their combination. TT homozygotes (but not A* carriers) for the FTO SNP, exhibited nominal associations between decreasing sleep duration and increasing BMI, waist circumference, visceral fat and HOMA-IR (all P
Published: 2012

27. Bone Dysplasia as a Key Feature in Three Patients with a Novel Congenital Disorder of Glycosylation (CDG) Type II Due to a Deep Intronic Splice Mutation in TMEM165

Author: Domenico Garozzo, Jaak Jaeken, Gert Matthijs, L Sturiale, M. H. Smet, M. Moens, F. de Zegher, and Renate Zeevaert
Subjects: chemistry.chemical_classification, medicine.medical_specialty, Mutation, Glycosylation, biology, Aspartate transaminase, medicine.disease, medicine.disease_cause, Disease gene identification, Article, chemistry.chemical_compound, Endocrinology, chemistry, Transferrin, Internal medicine, Lactate dehydrogenase, medicine, biology.protein, Creatine kinase, Congenital disorder of glycosylation
Abstract: Three patients belonging to two families presented with a psychomotor-dysmorphism syndrome including postnatal growth deficiency and major spondylo-, epi-, and metaphyseal skeletal involvement. Other features were muscular hypotrophy, fat excess, partial growth hormone deficiency, and, in two of the three patients, episodes of unexplained fever. Additional investigations showed mild to moderate increases of serum transaminases (particularly of aspartate transaminase (AST)), creatine kinase (CK), and lactate dehydrogenase (LDH), as well as decreased coagulation factors VIII, IX, XI, and protein C. Diagnostic work-up revealed a type 2 serum transferrin isoelectrofocusing (IEF) pattern and a cathodal shift on apolipoprotein C-III IEF pointing to a combined N- and O-glycosylation defect. Known glycosylation disorders with similar N-glycan structures lacking galactose and sialic acid were excluded. Through a combination of homozygosity mapping and expression profiling, a deep intronic homozygous mutation (c.792 + 182G>A) was found in TMEM165 (TPARL) in the three patients. TMEM165 is a gene of unknown function, possibly involved in Golgi proton/calcium transport. Here we present a detailed clinical description of the three patients with this mutation. The TMEM165 deficiency represents a novel type of CDG (TMEM165-CDG). This disorder enlarges the group of CDG caused by deficiencies in proteins that are not specifically involved in glycosylation but that have functions in the organization and homeostasis of the intracellular compartments and the secretory pathway, like COG-CDG and ATP6V0A2-CDG.
Published: 2012
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28. Infantile hypopituitarism: etiological variability evidenced by MRI

Author: M. H. Smet, F. de Zegher, Gilles Marchal, and Magda Vanderschueren-Lodeweyckx
Subjects: Pituitary stalk, medicine.medical_specialty, Pathology, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, General Medicine, Hypopituitarism, Aplasia, medicine.disease, medicine.anatomical_structure, Anterior pituitary, Diabetes insipidus, Medicine, Endocrine system, Radiology, Nuclear Medicine and imaging, Radiology, business, Neuroradiology
Abstract: In this study, magnetic resonance imaging (MRI) was performed to document potentially present morphostructural abnormalities of the hypothalamopituitary region in seven infants (age 0–21 months) who presented very early in life with clinical and biochemical evidence of hypopituitarism. Four infants had associated congenital cerebro-facial malformations. The following anatomical abnormalities were identified in variable combinations: ectopic neurohypophysis absence of the pituitary stalk, extreme elongation of the pituitary stalk, aplasia of the anterior pituitary lobe and no identification of the hypothalamopituitary complex. MRI proved to be very sensitive in the identification of structural malformations of the hypothalamopituitary region in infants with or without cerebro-facial malformations. AllhwuLll the magnetic resonance image does not appear to be a good predictor of endocrine dysfunction, it provides us more insight into the precise aetiology of this disorder and may be therefore of diagnostic, prognostic and therapeutic importance.
Published: 1992
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29. Placental growth hormone and IGF-I in a pregnant woman with Pit-1 deficiency

Author: Ahmed Igout, M. Bougoussa, F. de Zegher, E. Van Herck, Georges Hennen, and Johan Verhaeghe
Subjects: medicine.medical_specialty, Pregnancy, Immunoradiometric assay, Endocrinology, Diabetes and Metabolism, Serum concentration, Biology, medicine.disease, Late pregnancy, Endocrinology, Internal medicine, Blood plasma, medicine, Gestation, Placental growth hormone, Normal range
Abstract: The respective contributions of pituitary and placental GH to circulating IGF-I in pregnant women have not been well established. We measured the serum concentrations of placental growth hormone (PGH) and IGF-I in a woman with pit-1 deficiency before, during and after pregnancy, resulting in the birth of a healthy child (not pit-1 deficient). Both PGH and IGF-I concentrations were below the assay detection limit before and after pregnancy. During pregnancy, PGH and IGF-I levels increased steadily; the concentrations of PGH and IGF-I in late pregnancy were comparable with levels previously measured in normal pregnancies. PGH and IGF-I concentrations were strongly correlated throughout pregnancy (r = 0.90; P = 0.002). PGH was undetectable in cord serum, whilst the IGF-I concentration was within the normal range. The findings of this case study corroborate the notion that PGH is the prime regulator of maternal serum IGF-I during pregnancy.
Published: 2000
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30. Influence of duration of parenteral nutrition on retinopathy of prematurity

Author: Christine Vanhole, Karel Allegaert, Sophie Vanhaesebrouck, and F. de Zegher
Subjects: Male, Pediatrics, medicine.medical_specialty, Parenteral Nutrition, Time Factors, business.industry, Mortality rate, Visual impairment, Psychological intervention, Infant, Newborn, Obstetrics and Gynecology, Retinopathy of prematurity, General Medicine, medicine.disease, Parenteral nutrition, Pregnancy, Risk Factors, Pediatrics, Perinatology and Child Health, medicine, Humans, Female, Retinopathy of Prematurity, medicine.symptom, business, Retrospective Studies
Abstract: Prospects for premature infants have improved dramatically over the past 30 years. During this time, nutritional support has assumed increasing importance, not least because early interventions are now known to have long-term effects.1 2 Although the mortality rate has diminished, the proportion of surviving infants with severe sequelae has not.1 Retinopathy of prematurity (ROP) is the main cause of visual impairment in premature infants. It was associated with excessive oxygen use shortly after the initial description. However, even with careful oxygen …
Published: 2008

31. Preterm growth restraint:A paradigm that unifies intrauterine growth retardation and preterm extrauterine growth retardation and has implications for the small-for-gestational-age indication in growth hormone therapy

Author: F. de Zegher, Martijn Finken, Monique Rijken, J.M. Wit, Pediatric surgery, AGEM - Endocrinology, metabolism and nutrition, Amsterdam Reproduction & Development (AR&D), and Other Research
Subjects: Adult, Male, medicine.medical_specialty, Birth weight, Population, Preeclampsia, Pregnancy, Medicine, Humans, education, Growth Disorders, education.field_of_study, Fetus, Fetal Growth Retardation, business.industry, Obstetrics, Human Growth Hormone, Infant, Newborn, Gestational age, Infant, medicine.disease, Pediatrics, Perinatology and Child Health, Infant, Small for Gestational Age, Gestation, Small for gestational age, Female, business
Abstract: Small for gestational age (SGA) is defined as a birth weight and/or length >2 SDs below the gender-specific population reference mean for gestational age. However, there is confusion about various aspects of this term, as recently discussed.1,2 The term “intrauterine growth retardation” (IUGR) is often used for the same condition but preferably should be restricted to poor growth during pregnancy according to intrauterine growth diagrams used in obstetrics.3 SGA after a normal duration of gestation (37–42 weeks) is usually followed by rapid growth after birth (catch-up growth). It has been demonstrated that almost 90% of term SGA infants catch up in height in the first 2 years of postnatal life.4,5 On average, the human male has a birth length of 51 cm after term gestation and a final height, in the Netherlands, of 184 cm. Thus, in the 9 months before birth, he has reached almost 30% of his adult height potential. Fetal length velocity at midgestation is >10-fold higher than pubertal peak height velocity (Fig 1). Thus, very preterm infants are exposed to extrauterine life during a period that normally is characterized by rapid intrauterine growth. To survive, their energy expenditure shifts from growth-promoting actions to survival strategies to cope with the increased requirements of unintended postnatal life. Extrauterine growth retardation (EUGR) is often the result. Preterm infants whose mothers suffered from conditions such as preeclampsia are usually already growth-retarded at birth. Nonetheless, regardless of whether the child is born SGA, very preterm infants tend to be small at term, and a considerable proportion of them even meet criteria for SGA by that age. A study among 52 … Address correspondence to J.M. Wit, MD, PhD, Department of Pediatrics, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, Netherlands. E-mail: j.m.wit{at}lumc.nl
Published: 2006
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32. Polycystic ovaries after precocious pubarche: relation to prenatal growth

Author: Adriana Jaramillo, Abel López-Bermejo, F. de Zegher, David B. Dunger, Lourdes Ibáñez, Elisabet Miró, and Goya Enríquez
Subjects: Adult, medicine.medical_specialty, Adolescent, Birth weight, Puberty, Precocious, Ovary, Prenatal care, Medicine, Precocious puberty, Birth Weight, Humans, Child, Gynecology, business.industry, Rehabilitation, Hyperandrogenism, Obstetrics and Gynecology, Ultrasonography, Doppler, medicine.disease, Polycystic ovary, medicine.anatomical_structure, Carotid Arteries, Reproductive Medicine, Cohort, Female, business, Body mass index, Polycystic Ovary Syndrome
Abstract: BACKGROUND: In 1998, we revealed a sequence departing from prenatal growth restraint in girls and evolving, through precocious pubarche (PP) in mid-childhood, towards anovulatory and hyperinsulinaemic hyperandrogenism. The latter condition fulfilled the criteria for the diagnosis of polycystic ovary syndrome (PCOS), which was then defined independently of the presence of polycystic ovaries (PCOs). Since 2003, the diagnosis of PCOS has been extended by adding PCO as an alternative criterion. We verified longitudinally over 28 ± 2 years the prevalence of PCO and its potential relationship to growth before birth in a group of post-PP women (n = 14, mean age = 28 years; body mass index = 24.3 kg/m 2 ) belonging to the original cohort of 35 girls in whom the PP-PCOS sequence was described. METHODS: Endocrine-metabolic variables, body composition (by dual-energy X-ray absorptiometry), carotid intima-media thickness (IMT) and ovarian morphology by transvaginal ultrasonography were assessed in all women. RESULTS: Post-PP women with a birthweight (BW) in the lowest quartile, when compared with post-PP women with a higher BW, had smaller ovaries (mean volume = 4.0 versus 9.0 ml; P = 0.004) and a much lower prevalence of PCO (0 versus 67%; P = 0.006). The remaining variables were similar between BW subgroups. CONCLUSIONS: The presence of a PCO morphology in women with a PP history was found to relate to prenatal growth. It would be of interest to verify whether a similar relationship exists in anovulatory and/or hyperandrogenic women without PP history.
Published: 2006

33. Association of aromatase (CYP 19) gene variation with features of hyperandrogenism in two populations of young women

Author: Ken K. Ong, Lourdes Ibáñez, Clive J. Petry, K. F. Michelmore, Dianne L. Wingate, F. de Zegher, David B. Dunger, S. Artigas, and Adam H. Balen
Subjects: medicine.medical_specialty, Adolescent, medicine.drug_class, Population, Puberty, Precocious, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Aromatase, Internal medicine, medicine, Humans, education, Child, Testosterone, education.field_of_study, Base Sequence, Rehabilitation, Hyperandrogenism, Obstetrics and Gynecology, Genetic Variation, DNA, Androgen, medicine.disease, Polycystic ovary, United Kingdom, Endocrinology, Genetics, Population, Reproductive Medicine, Haplotypes, Spain, Case-Control Studies, biology.protein, Population study, Female, Insulin Resistance, Polycystic Ovary Syndrome
Abstract: BACKGROUND: Aromatase catalyses the conversion of androgens to estrogens and thus variation in the aromatase gene could contribute to female syndromes of androgen excess, such as precocious pubarche (PP) and polycystic ovarian syndrome (PCOS). METHODS: Two groups, one case – control containing girls from Barcelona, Spain with PP (n 5 186) or healthy controls (n 5 71), and the other a population study of young women from Oxford, UK, who volunteered for a study of normal women’s health (n 5 109), were genotyped at four aromatase gene haplotype-tag single nucleotide polymorphisms (SNP). Clinical features and hormone concentrations relevant to hyperandrogenism were compared across haplotypes or genotypes. RESULTS: Distributions of aromatase haplotypes ( P< 0.0001) and aromatase SNP_50 genotype (P 5 0.001) were significantly different between PP girls and Spanish controls. The AGGG haplotype was associated with an odds ratio (95% confidence interval) of 0.5 (0.3– 0.9) (P 5 0.005) for the presence of PP compared to GAGG. In 84 post-pubertal PP girls, aromatase haplotype was associated with functional ovarian hyperandrogenism ( P< 0.05), independently of insulin sensitivity. In the Oxford population, SNP_50 was associated with variation in PCOS symptom score (P 5 0.008) and circulating testosterone concentrations (P 5 0.02). CONCLUSIONS: This study suggests that common variation at the aromatase gene (and not just rare loss-of-function mutations) is associated with androgen excess in girls and young women.
Published: 2005

34. A neonatal form of isolated ACTH deficiency frequently associated with Tpit gene mutations

Author: Alain Enjalbert, Anne Barlier, Jacques Drouin, M de Vroede, Michel David, Raja Brauner, Felix G. Riepe, Begüm Atasay, Sule Yigit, P Dechelotte, Anne-Marie Pulichino, Leo Dunkel, Cheri Deal, F. de Zegher, B. Pigeon, M. Gueydan, Merih Berberoğlu, K Noordam, Martin Fassnacht, Juan J. Heinrich, Juliane Léger, Wolfgang G. Sippell, Carl-Joachim Partsch, Georges Malpuech, Sophie Vallette-Kasic, Jennifer H. Kyllo, Jacques Weill, Thierry Brue, Patricia A. Donohoue, and G. Van Vliet
Subjects: Genetics, Homeodomain Proteins, Mutation, Steroid Metabolism, Inborn Errors, Infant, Newborn, Steroid Metabolism, Genes, Recessive, General Medicine, Biology, Gene mutation, medicine.disease, medicine.disease_cause, Endocrinology, Adrenocorticotropic Hormone, medicine, Isolated ACTH deficiency, Humans, Adrenocorticotropic hormone deficiency, T-Box Domain Proteins, Gene, Transcription Factors
Published: 2005

35. 40(th) EASD Annual Meeting of the European Association for the Study of Diabetes : Munich, Germany, 5-9 September 2004

Author: S. Artigas, A V Dreval, Mark I. McCarthy, C Watson, Peter H. Bennett, M Quint, Y Ikeda, E Alpert, F Schiele, H Sekihara, Erik Gylfe, P Lowe, J Kuhlmann, Alain Golay, V Longo, Shahidul Alam Khan Akm., L G Mantovani, M Zawodniak-Szalapska, G Winkler, T Harrity, L Virág, U Johne, Kuo S-W., Linda C Tapsell, J Rodriguez, Michel Komajda, K Kankova, Carole A. Cull, M Sporna, E Estilles, U Ribel, M C Spruce, E Buzzigoli, T Prazak, J K McLaughlin, M K Lingohr, M Lim, F Calara, A Siebenhofer, G Meregalli, Roberto Anichini, A D Baron, R Kurashvili, P C Butler, G I Fantus, T. E. De Gooyer, Park Y-M., R. Walther, S Heinrich, Agnieszka Zawiejska, S Mukherjee, Nikolaos Papanas, G Wong, Ian D. Caterson, David M. Maahs, Shuichi Kaneko, Alexandra E. Butler, Francisco Javier Ampudia-Blasco, O N Kong, Attali J-R., C A Hedman, K Oshinyemi, Nicolle Müller, I C Cranston, N Okumus, M V Vlaiculescu, Balasubramanian Ravikumar, W W Cheatham, K Mukasa, K B Biswas, Annunziata Lapolla, Phil McEwan, G Mader, Gilles Chassot, Dragi Anevski, Werner A. Scherbaum, M Donath, C Hesselmann, R A Gandhi, David E. Moller, Ezio Bonifacio, C Garcia, V Ifandi, P Hornnes, Nieuwenhoven Fav., C Puech, S Pérez-Del-Pulgar, Kim S-R., G Hines, C Rubio Terrés, Michael Gaster, N. Hosszufalusi, A Scholze, Andrew A. Young, Stavros Liatis, F Hariri, S Tan, Paul Valensi, Allan E. Karlsen, J Kim, E. Moberg, J Kaiser, L Berman, G Nelson, A Altkrüger, P Kothare, D B Cook, S Doran, G. van Dijk, Shahnaz Shahinfar, Kim C-S., P Stahl, M Manousaki, S Sigrist, S K Lim, M. P. Stern, A Guberti, C Rezzani, J McKenney, Karl Thomaseth, Sofia Carlsson, M Julia, R Brillante, I Rubesova, T Darkow, E Matsumoto, Wendy M. Macfarlane, M Di Martino, G Bardini, Rossella Menghini, D Duhot, E Farcasiu, Annalisa Natalicchio, I Lindner, J Buvat, Christian L. Brand, Harry Dorchy, Iwona Pietrzak, Z T Luo, P Home, M Ekelund, Jesper Gromada, Kristine Færch, F Piarulli, H Kim, R Mentel, Zsuzsanna K. Zsengellér, Dullaart Rpf., Anton Luger, Thomas A. Pearson, V Manicardi, P Rösen, Feng Y-M., R Morganti, Lars Hansen, Demuth H-U., Haruo Kasai, A Shostak, Rudi Steffensen, G Taylor, Markolf Hanefeld, C Santini, E Hamaguchi, Roberto Miccoli, F Storms, M Cooper, Y Lee, Allison E. Aiello, P Smith, T Suehiro, K Treece, M Waluś, Timothy A Welborn, Simone Baltrusch, E Kontela, S Chai, J Crean, H Yokoyama, Johan G. Eriksson, Rafael Hernández Hernández, J Rodríguez-Saldaña, M P Tornero, G Formoso, D. Lovell, E Bingham, A Mylonakis, M Manteghetti, D Fedele, Antonio Martín-Duce, Ralph A. DeFronzo, D Salcedo, Kurt Højlund, Antonio Petrone, Sheu Whh., C Gutierrez, Flavia Pricci, S Kurita, Z G Abbas, M M Benedetti, Philippe A. Halban, Daniel J. Cox, O Ljungkvist, Justine Davies, J Palsgaard, Lars Sjöström, E Bosi, L Janin-Manificat, W. F. Kelly, M. Fernandez, E Colak, O V Mulyarchik, B Kronshage, F Lang, M Erfurth, Takashi Kadowaki, N Jendrike, U Walter, J Wishart, Y. Neye, D Kim, N Furuhashi, M Barsotti, D Florow, L Ke, L Borgquist, N C Jackson, Ffolliott M. Fisher, V Baskar, K Yoshioka, Bryan A. Wolf, G Chabrier, R Skoumal, Livio Luzi, H Kose, I Pharisien, B. Klein, H Winiarska, M C Johnson, L Griffiths, Nonna Kravchun, C Combe, Baptist Gallwitz, J Zdychova, L Skorda, Jorma Ilonen, W Gao, I N Steen, A Terrinoni, P D Ambery, W Kern, C M Kusminski, Cho M-H., Paolo Pozzilli, Louise G. Grunnet, E Schönle, David R Matthews, Robert W. Taylor, Y Cohen, Kim H-S., M P Eccles, N B Tutuncu, D McDowell, Richard M. Bergenstal, K Takamatsu, T Steiner, Jaan Palgi, Valdemar Grill, N Niculescu, G Federici, S Lehto, P. M. McKeigue, M Barone, Michael E. Trautmann, S Smirnov, J Mannion, M Eto, C Rousseau, M Conti, C S Ernest, Antonio Ceriello, D H Schweitzer, Jung E-D., Andreas Festa, Avijit Lahiri, A Shepelkevich, A Murro, A Kollmann, Jonathan R.S. Arch, R Landgraf, Son H-Y., I Engelsberger, E Agardh, S Rodríguez-Mulero, P J Kraml, K Lee, D. F. Du Toit, E Kim, G Fadini, Williams Ajk., Philip Home, M B Antcieferov, C Perlemoine, D Perrea, Song X-L., D Ruggieri, Krister Bokvist, Heidi Sørensen, Bilbao, G Yoshino, J P Taylor, Shen H-M., S M Furier, R Urquhart, J Wohlgelernter, Jianping Weng, T. Baba, Q Hong, C Silva, Castaigne J-P., M Felaco, X X Zhang, M Jaroň, Milla Rosengård-Bärlund, J G Papp, Toshio Miyata, Lervang H-H., Park M-K., I Kinalska, A Long, Oomen Phn., N Kogawa, Ippolita Patrizia Patera, S. Karadeniz, Dinesh Selvarajah, D S Chung, A Wensaas, Richard Imrich, M Recasens, J Ruxer, O Buchea, E Wilpart, S P Stepanenko, Le Ttd., H Ohgawara, Mariaconsuelo Valentini, A Mondok, M Peltonen, Marianne O. Larsen, K Chatzianagnostou, Agneta Ståhle, A L Ferrari, L Bordier, F Maingrette, A Matsuda, G Vukomanovic, Jakob D. Wikstrom, T Yamakita, E Gorostiaga, J Jin, B Gopalan, Heinz Drexel, S Hewitt, Rury R. Holman, C Dieterle, T L Ruchti, N Asatiani, M Sidira, A Iezzi, A J Sommerfield, D Châtenet, M L Olsen, R Bergemann, C Koehler, T L Kuraeva, B Balas, Christian Berne, E Santos-Mazo, G Smith, A Siejka, R Kožnarová, A Mattina, S Sheikh, A Adomeit, M Rasmussen, J. Fagerudd, N Busciantella Ricci, Nuria Vilarrasa, E Hammar, T L Thoms, L Aydın, Ron G. Rosenfeld, A Nikolajuk, R Gos, C L Morgan, H L Yu, D Dheelchand, S Ramrath, N Boudriga, Jerome I. Rotter, C Jahannault, W M Weston, Folke Lindgärde, M Hertlova, D Knight, A Monroy-Mayorga, E Pardini, A Chamson-Reig, B Franke, Janie McCluskey, Joseph Bryan, C Nikolopoulou, Christie M. Ballantyne, Fausto Santeusanio, L Pegoraro, M Lee, A Klimenko, S Jaiveer, K. Pettersson-Fernholm, Michael A. Nauck, A Ekbom-Schnell, G Deferrari, Riccardo Schiaffini, S. Pampanelli, Khan Aka., David Hopkins, Maija Wessman, M Kamarinos, Noh J-H., O Ebisui, K McCarroll, Jeppe Sturis, Peter Nowotny, N Gorbenko, Åke Sjöholm, David G. Maggs, A E Halseth, B Cresci, A A Ortiz-Gress, A Korakovouni, O Matejkova, C E Mogensen, C J Lin, Ramon Gomis, H Seaman, C Granier, Yang C-H., F Assah, O Sanchez, Fausto Machicao, Peter G. Morris, Alberto Ortiz, A Giardinelli, D Bracaglia, A Gonzalo, S Pavlatos, Andreas Lechner, F Canovic, L Sjolind, Allan Vaag, Birgitte Bruun Nielsen, David A. Ziegler, Vito Lampasona, R Gershoni-Baruch, A. Dei Cas, H Renz, E Mena, Matthew Waltham, Kim D-M., H Levanen, D D Mick, Valentina Alexandrovna Peterkova, E Meskhishvili, Sarah Nutland, R Bustani, John R. Lindsay, M Christoforidou, A Abicht, E Harno, K Cyganek, A Fitchet, S Neelotpol, P Nikishin, P Serradas, J Hinrichsen, M Halvorson, M Chovatia, B Voet, Jinny Willis, E Parretti, M Haslbeck, M Wellard, L Teng, Julio Wainstein, J S Fischer, K. Lalic, D Roggenland, I Gich, R Anwar, Maurizio Cassader, D Serota, X J Li, R J Schotzinger, Vilmundur Gudnason, Björn Zethelius, S A Wootton, W Andrzejewski, R Rezsohazy, R Gao, T Klimentova, T Mazurek, I Bruckner, C Dohrmann, R E James, G daSilva Xavier, Kim S-Y., A Dorca, Stuart J. Pocock, Terri J. Allen, I Giovos, P B Parab, N H Andersen, P Fotinakis, Miriam Cnop, H Lee, Norbert Tennagels, Omorodola I. Abatan, F Ailett, I. Lager, D Manzella, H Hut, Larry A. Distiller, G Lip, Lim S-K., Rong Zhang, T Tsuno, Steen Knudsen, M. Bajardi, Manuel Benito, Dai Sugimoto, Melvin J. Prince, D W Dunstan, D Rankins, K A Majali, G Ozansoy, Isabella Russo, S Uçak, G Annuzzi, R Talar-Wojnarowska, K Lange, S Neugebauer-Baba, Campbell H. Thompson, Eric Renard, P. D. Mountjoy, Z Morrison, Elizabeth A. Davis, Franco Cavallo, C Corvaja, R Antuña, Craig John Currie, H Linnebjerg, He Y-L., A J Palmer, Mariola R. Chacón, H Malinska, M. Jones, R Lichnovská, K Mandes, Paolo Tessari, T Mokhort, A Laina, H. L. Y. Chan, I Schmidt, R Banks, Richard G. IJzerman, L Ksinantova, G Setti, H Vaudry, A Gallo, V Spallone, Chen J-W., Thomas Danne, A Chong, M Hallschmid, S Aczel, S Hulme, N Islam, M Hosoi, P M Ternan, P Di Bartolo, N Bishara, T Shibasaki, Martin A. Osterhoff, Im S-S., M Jecht, T Hamaguchi, S Mattera, K Ways, Elizabeth Northam, U Rajala, Reinhard W. Holl, L Yang, S Panaiotopoulos, K Horvath, R Kluge, Thora B. Bodvarsdottir, Y Dong, Irene Alemanno, C McDougall, Reimar W. Thomsen, M Campbell, W Rabl, John Öhrvik, Yuichiro Yamada, Paola Ungaro, W Benzer, Mike Sampson, Roberto Trevisan, R G Radu, Aas A-M., P E Lobo, Ricardo Scott, S M Son, Josephine M. Forbes, T A Hillier, K L Wyne, Louis L. Nguyen, J Farmer, M H Tan, Kwon H-S., J Yang, L Sandvik, Franco Folli, A K Jenum, M Nguyen, W Pratipanawatr, A L Frederiksen, Rebecca Smith, Lee H-J., A Schäfer, C Manuelli, G S Denver, T Vukovich, B Maceira, K Matsumoto, K. Chokkalingam, Nurcan Üçeyler, P Modi, Timothy M. Morgan, S Mertens, B M Singh, Michaela Riedl, K Iso, C Cucurullo, G. F. Bottazzo, M Calvani, K Hur, J Wetzels, Kazuhiro Takahashi, Y Aso, H Stammer, M G Masding, Fitsum Guebre-Egziabher, J L González-Sánchez, L Armstrong, Alberto Maran, Peter G.F. Swift, S S Popovic, J Starczynski, E Vitacolonna, Luigi Laviola, R W Gelling, Marina Cardellini, D Barilla, Rosa de Diego Martínez, W H Landschulz, Anne Mette Rosenfalck, R K Wong, Kevin E. Schneider, K Peros, Giuseppe Nanni, F Zhang, I Rákóczi, T Iburi, M Nakhjavani, X Q Zhang, S Tournis, Per Lav Madsen, Graham A. Hitman, A. Tura, K Laubner, N D Kostic, Lawrence M. Dolan, R. Sinha Roy, J A Wagner, J. Tuomilehto, J Hauptman, M Abdel-Ghany, D Lacombe, Toralph Ruge, Johannes A Maassen, Triantafyllos Didangelos, K Sasaki, I Argüelles, Klaus Levin, C Popow, Emanuel Christ, R Chetty, L Baillet-Blanco, Jo-Ann Salmon, T Mine, James L. Trevaskis, I Franke, J Gorski, E A Andrianova, A Dayan, A Caballero, Aleksandra Gilis-Januszewska, M Yasujima, Z Kasalová, C.D.A. Stehouwer, F. K. Gorus, G A Nichols, A Glowania, David P. Strachan, P Fredlund, N. F. da Silva, P Reboldi, M Sausbier, K H Groenier, G Stuccio, N Guttman, K R Ahmed, A D Ristic, T Kapellen, J Coutcher, Aldo V. Greco, Oswald Wagner, A Zagayko, Maria Alevizaki, B B Zhang, W F Ferris, Jenny Fredriksson, Lois Jovanovic, J Hänninen, R De Giglio, Kazuo Yagui, O Potterat, P Hamliton, R E Scranton, B Mankovsky, A Stylianou, B Fellström, Abdel-Wahab Yha., M Kitagawa, Katherine L. Baldock, F R Johnson, F Baigts, S D'Addato, F J Sanz, A Mistry, S D Wise, T Pratipanawatr, U R Fölsch, James R.C. Parkinson, Claudia Sommer, C Park, F E Griffiths, M L Martí, R Demirtunc, S Taniguchi, J Lundkvist, T Siegmund, Juan Sztajzel, C Dienesch, F Baumgartner, L Scalone, T M Mckolanis, K Otake, Ullrik Pedersen-Bjergaard, T M Vriesendorp, Michael B. Wheeler, Henry Schmitt, Peter Hovind, S Lange, Stephane Roze, L. Van Gaal, B Klaproth, Anthony E. Civitarese, D Eckland, A Dagar, D F Hopkins, Kari Stefansson, C Gonzalez-Yanes, B Meyboom-de Jong, D. J. Betteridge, K Buhling, M Crepaldi, Ana M. Wägner, L Renna, L Volpe, R McBride, V Corbo, E O Brennesvik, R P Hayes, R Abdollahnia, G Viviani, C F Liew, Francisco Pérez-Bravo, Jeffrey Baron, Brian M. Frier, H H Samira, D Szentendrei, K. J. Schjoedt, W K Waldhäusl, D Gniuli, D Zou, G Tschank, V Urbančič, A L Nolan, Albertini J-P., J Malcomson, M Larbig, C Cheyssac, K Aurich, C M Kesson, S Heller, Maija E. Miettinen, R F Luco, Adrian J. Cameron, Luigi Mattiello, Z. Metelko, X E Zhang, M Parramón, I. G. Obrosova, J Fruchart, M Ilic, Björn Eliasson, Gilles Chatellier, M A Martín, D M Kendall, Holger Luthman, V F Varillas, D Maccubbin, Jang S-A., Amalia Gastaldelli, E Salzsieder, P. de Mol, A Yoshida, H D Lindner, D Gostiljac, M Just, Pan C-Y., J M Fujitaki, G Eiermann, K Bergenheim, A D Frick, A Agacdiken, K Varytimiadis, K Cseh, D A Jackson, S Calderari, Dena G. Hernandez, H M Liebich, K Min, F. de Zegher, Bernd Kulzer, K Han, Ulrich A. Müller, D Marrero, H Hatakeyama, René Koopman, Doo H-K., Petr Wohl, P. Sharp, P Forder, Thor Aspelund, N Meneveau, R M Schmülling, R Aubert, Thom Sam., H Youshikawa, M Ankelo, D Bowden, I Kelly, Frédéric Fumeron, M Sartini, Robert S. Sherwin, L Varadhan, A Criscimanna, John Betteridge, V Jelic, M Bartnik, N Lemke, B Ursø, A Bertoldo, A M Owona, H Okochi, L Pérez-Tamajó, S L Monfre, Daniel Brandhorst, K T Legg, Andries J. Smit, Veronica Sancho, Masashi Hirai, C Klein, Paul J. Thornalley, A Chaidaroglou, K Miura, B Zinman, O M Dvoynishnikova, J Plank, Jan Bolinder, C Lush, B Rubi, R Pozzilli, M Bashir, S A Shtandel, F Mosca, A Naskalska, Josef Vcelak, U Sausbier, P Cavaiani, T U Baehring, Michele Solimena, P Formisano, M Rastaldi, Bernard Thorens, J Ruzzin, E Arbit, M. Hori, Torkel B. Brismar, E Soltes Rak, A Filo, P Heinke, Matthew P. Coghlan, M Masotti, I Perevozskaya, K Ahn, I Moules, K Van Dyck, I Goldstein, Z Mathe, G Z Zhao, S Fajardo, J Taylor, S Chrul, J C Pareja, D Hadjidakis, A J Scheen, N Siddiqua, D C Cavan, R Grella, Krabbe S, H J Rochlitz, A E Hinkkanen, W Wilpshaar, Richard Stevens, M Dreyer, S Hara, X Wang, Melania Manco, D Gillen, Magalie A. Ravier, Olli Simell, John C. Lawrence, Kohnert K-D., Agardh C-D., A Berghold, L Kristensen, Grant Sfa., N Gursoy, Leif Groop, N Freemantle, Anja Schweizer, L Pala, Legros J-J., C. Di Pietro, N. Yamamoto, J Magyar, B Nikolovski, H Ikeda, D Lee, Bruce A. 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Leon, Alberti Gkm., A Opel, S Kokkoris, S B Hong, Philippe Courtois, L Haque, Maria Sörhede Winzell, M C Beauvois, A Szypowska, D Yu, M Gutniak, D Petzinna, B Isomaa, K S Prickett, Maria Felice Brizzi, Pavel Hamet, P J Hammond, K. F. Michelmore, Yumie Takeshita, N Hariharan, Corrado M. Cilio, G Pogatsa, W G Jerome, E Bartley, K Schlembacher, G Blohmó, Guy A. Rutter, Kyung Mook Choi, S. C Tamer, Felix K. Assah, K A Jandeleit-Dahm, M Chan, H Darius, Jørgen F. P. Wojtaszewski, A Papazisi, M Amaya, A Knopff, M Tadayyon, I J Kim, W Russ, T Myrnäs, M. Tryon, S Poonsatha, Noel Cameron, Kim M-H., Alejandra Tomas, F Homo-Dekarche, G. Di Cianni, M Stotzka, C Solimine, Mikhail Borisovich Antsiferov, H Naserke, M Bianchi-Biscay, J I Lara, Moon C-K., Alain Ktorza, Alison N. Jeffery, V Lilla, Eun Seok Kang, Hanley Ajg., J Widder, R Ratner, C Goretti, P J Weston, J Perkins, V Rasmussen, M Evans, T M Gibson, A Jaffe, S I Chisalita, C Owman, L Hiltunen, E Kakishita, C M Mack, H C Potter, M Femerling, M Desai, M Soinio, K Yang, Patricia L. Brubaker, M Meyer, V Dy, J Berden, R Komers, Milos Adamec, R Petzoldt, Alan G. Robinson, R Stevens, A Doi, A Leunda, Eduard Montanya, Alessandra K Cardozo, N Kraenkel, Claudio Cobelli, U A Mueller, S Yamashiro, B R Gedulin, G Francisco, J Dennenmoser, Lesch K-P., Martin G. Bischof, M Ichita, C Fernandes, Jochen Hampe, S Kern, D Kelly, E Zeender, P Perna, J D Best, A C Calkin, Vivian Fonseca, J Prestle, D G Parkes, Satish K. Garg, T Burrell, B M Fischer, D Kruger, J S Skinner, Lin T-M., Jozef Ukropec, Maria Jeziorska, K Arii, David D. D’Alessio, M B Gomes, L Quandt, I Fragaki, M C Brindisi, A Gladkih, E Kitsou, S Di Cola, T Iwasaki, Peter Diem, T Lakka, V V Popova, G Lee, Hannah J. 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Paulin, S, Marcu, S, Tauveron, I, Zimmermann, C, Schiele, F, Seronde, M, Vautrin, P, Lusson, J, Thieblot, P, Bernard, Y, Mistry, A, Pye, M, Peovska, I, Maksimovic Pavlovic, J, Vavlukis, M, Pop Gorceva, D, Bosevski, M, Scognamiglio, R, Negut, C, De Kreutzenberg, S, Madonna, R, De Caterina, R, Willerson, J, Geng, Y, Vahsen, S, Ledwig, D, Ramrath, S, Frantz, S, Schmidt, I, Calvillo, L, Dienesch, C, Elbing, I, Bischoff, H, Ertl, G, Bauersachs, J, Davydov, A, Mkrtum'Yan, A, Baranova, L, Ikeda, Y, Suehiro, T, Osaki, F, Ota, K, Arii, K, Kumon, Y, Hashimoto, K, Doney, A, Morris, A, Palmer, C, Byun, S, Doo, H, Pagnin, E, Calo, L, Fadini, G, Kubaszek, A, Chai, S, Chai, Q, Rasmussen, L, Ledet, T, Wogensen, L, Lengyel, C, Varró, A, Virág, L, Magyar, J, Bíró, T, Jost, N, Skoumal, R, Nánási, P, Tóth, M, Horkay, F, Papp, J, Zacharopoulou, O, Athanaselis, S, Tsokos, N, Doupis, J, Psallas, M, Cokkinos, D, Pavlatos, S, Liatis, S, Akhobadze, T, Dzneladze, L, Samarguliani, I, Taskiran, M, Rasmussen, V, Jensen, G, Fisher, A, Petrovsky, N, Srikusalanukul, W, Budge, M, Trifunovic zamaklar, D, Zivkovic, M, Jelic, V, Vukomanovic, G, Ristic, A, Seferovic, P, Costa, J, Duarte, S, Manley, S, Sailesh, S, Venkataraman, A, Haider, Y, Groza, I, Oprean, M, Ardelean, A, Morosanu, A, Darkow, T, Vanderplas, A, Mamas, M, Mcelduff, P, Burns, J, Edwards, R, Fitchet, A, Young, R, Gibson, J, Lichiardopol, R, Niculescu, N, Totora, A, Pencea, C, Tomescu, I, Cinteza, M, Manicardi, V, Coscelli, C, Navazio, A, Catellani, E, Michelini, M, Dall'Asta, D, Guberti, A, Piazza, A, Gasparini, E, Pantaleoni, M, Guiducci, U, Manari, A, Sejil, S, Janand delenne, B, Avierinos, J, Habib, G, Labastie, N, Vague, P, Lassmann vague, V, Luźniak, P, Tatoń, J, Wojciechowska Luźniak, A, Zairis, M, Lyras, A, Patsourakos, N, Tsirimbis, V, Foussas, S, Lupón, J, Urrutia, A, Herreros, J, González, B, Coll, R, Altimir, S, Prats, M, Valle, V, Abreu padí, C, Rábago, G, Ivanova, L, Brasacchio, D, Harno, E, Keenan, A, Li, H, Lu, Z, Ke, L, Liu, H, Jeong, I, Chae, M, Choi, M, Yoo, H, Kim, C, Yun, M, Na, M, Kang, Y, Kong, O, Son, S, Kim, I, Tanaka, N, Hosoi, M, Matsuyama, Y, Fukumoto, M, Yamakita, T, Yoshioka, K, Ishii, T, Sato, T, Fujii, S, Aoki, T, Shibata, T, Mizutani, N, Suzuki, J, Fowelin, J, Samuelsson, P, Brandrup wogsen, G, Okumura, K, Tokmakova, A, Staroverova, D, Antcieferov, M, Shutichina, I, Kuntchevich, G, Vriesendorp, T, Morélis, Q, Legemate, D, Schaper, F, Mainas, E, Gkioulmpasanis, I, Panagiotou, I, Vassilikos, G, Skorda, L, Sidira, M, Christoforidou, M, Alaveras, A, Artikis, V, Evdemon, E, Lechleitner, M, Koch, T, Ebenbichler, C, Sturm, W, Moretti, L, Moruzzo, D, Boldrini, E, Pandolfo, C, Kameyama, M, Iwasa, R, Cho, M, Nam, J, Huh, K, Kaplar, M, Paragh, G, Erdei, A, Csongradi, E, Garai, I, Varga, J, Galuska, L, Udvardy, M, Higa, M, Kaneko, Y, Hiroi, N, Koziarska, D, Nowacki, P, Majkowska, L, Luzniak, P, Wojciechowska luźniak, A, Tushuizen, M, Nieuwland, R, Snoeck, D, Sturk, A, Diamant, M, Aguiar, L, Bahia, L, Villela, N, Laflor, C, Conde, C, Bottino, D, Dorigo, D, Bouskela, E, Pu, S, Luo, Z, Lam, K, Dan, Q, Xu, A, Shen, J, Cheng, K, Xu, J, Thamer, C, Stefan, N, Haap, M, Heller, E, Tschritter, O, De Prado, A, Ortiz, A, Ybarra, J, Gich, I, Pou, J, Ehren, M, Roggenland, D, Reinsen, B, Klein, H, Rittig, K, Stock, J, Kocher, B, Balletshofer, B, Shon, H, Chung, D, Nakatani, Y, Matsuhisa, M, Kaneto, H, Hatazaki, M, Yoshiuchi, K, Katakami, N, Kawamori, D, Ohtoshi, K, Sakamoto, K, Matsuoka, T, Ozawa, K, Ogawa, S, Hori, M, Yamasaki, Y, Zitouni, K, Harry, D, Nourooz zadeh, J, Earle, K, Olesen, P, Franco, L, Corvaja, C, Semplicini, A, Ceylan işık, A, Arı, N, Rösen, P, Lee, I, Park, K, Jung, E, Shin, D, Jo, S, Obuobie, K, Prakash, P, Hanna, F, Lazarus, J, Varadhan, L, Gurushankar, J, James, D, Sheikh, S, Gaede, P, Zou, D, Vilarrasa, N, Perez maraver, M, Mena, E, Perez, D, Setti, G, Buckingham, R, Urbančič, V, Stefanovska, A, Bernjak, A, Ažman juvan, K, Kocijančič, A, Glowania, A, Filters, T, Fosmark, D, Torjesen, P, Kilhovd, B, Berg, T, Sandvik, L, Hanssen, K, Mentink, C, Donchenko, G, Stepanenko, S, Maingrette, F, Deng, H, Lindenmair, A, Freudenthaler, A, Baumgartner parzer, S, Nizheradze, K, Khoruzhenko, A, Tronko, N, Sheu, W, Ou, H, Shen, H, Lin, T, Wu, H, Yang, C, Mogylnytska, L, Schmoelzer, I, Davies, J, Band, M, Struthers, A, Prázný, M, Škrha, J, Kasalová, Z, Neelotpol, S, Jahan, P, Kauschke, S, Harrop, C, Schäfer, A, Widder, J, Eigenthaler, M, Walter, U, Uchimura, I, Ikebukuro, M, Kaibara, M, Hirata, M, Helal, R, Pervin, F, Yang, X, Jansson, P, Nagaev, I, Jack, M, Carvalho, E, Sunnerhagen, K, Cam, M, Cushman, S, Smith, U, Creely, S, Farmer, J, Gustafson, B, Kusminski, C, Krusinova, E, Wohl, P, Klementova, M, Lanska, V, Mcdougall, C, Kelly, I, Abbas, Z, Lutale, J, Archibald, L, Karunajeewa, H, Stingemore, N, Stuccio, G, Mcgechie, D, Muller, L, Hak, E, Goudzwaard, W, Montorsi, F, Homering, M, Sprenger, K, Goldstein, I, Asnaghi, V, Ferrari, G, Rastaldi, M, Gabellini, D, Dell'Antonio, G, Maestroni, A, Ruggieri, D, Luzi, L, Piemonti, L, Zerbini, G, Anafaroglu, I, Tutuncu, N, Sultana, M, Siddiqua, N, Iwasaki, T, Nakajima, A, Yoneda, M, Mukasa, K, Tanaka, S, and Sekihara, H
Subjects: 0303 health sciences, medicine.medical_specialty, business.industry, EASD, Endocrinology, Diabetes and Metabolism, Human physiology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Family medicine, Internal Medicine, Medicine, business, 030217 neurology & neurosurgery, 030304 developmental biology
Published: 2004

36. Prevalence and demographic features of childhood growth hormone deficiency in Belgium during the period 1986-2001

Author: G Massa, J. De Schepper, Margarita Craen, M. V. L. Du Caju, Marc Maes, F. de Zegher, G. Thiry-Counson, J P Bourguignon, Muriel Thomas, Claudine Heinrichs, Faculty of Sciences and Bioengineering Sciences, Vrije Universiteit Brussel, and Faculty of Medicine and Pharmacy
Subjects: Male, Parents, medicine.medical_specialty, Pediatrics, Adolescent, Pituitary Diseases, Endocrinology, Diabetes and Metabolism, Birth weight, Severity of Illness Index, Growth hormone deficiency, Age Distribution, Endocrinology, Belgium, Internal medicine, Epidemiology, Severity of illness, Prevalence, medicine, Birth Weight, Humans, Sex Distribution, Child, Belgium/epidemiology, Growth Disorders, Pituitary stalk, Human Growth Hormone, business.industry, Infant, Newborn, Infant, General Medicine, medicine.disease, Human Growth Hormone/deficiency, Body Height, Ectopic Posterior Pituitary, El Niño, Pituitary Diseases/complications, Child, Preschool, Etiology, Female, Human medicine, Growth Disorders/drug therapy, business
Abstract: OBJECTIVE: Since the availability of recombinant human growth hormone (rhGH) all children with growth hormone deficiency (GHD) living in Belgium are offered rhGH treatment after approval by a peer-review board. In this study, we evaluated the prevalence and demographic features of childhood GHD in Belgium during the period 1986-2001 and we compared them with the data from other countries. METHODS: Diagnostic, demographic and baseline auxological data of 714 children diagnosed as having GHD between 1986 and 2001 were retrieved from the database of the Belgian Study Group for Paediatric Endocrinology. RESULTS: The prevalence of GHD in Belgium was estimated to be 1/5600. The origin of GHD was idiopathic (idGHD) in 41% of the patients, congenital (congGHD) in 20% and acquired (acqGHD) in 35%. During the first 4 years (1986-1989) more patients were classified as idGHD; thereafter the distribution between the three aetiology groups did not change. In all groups, boys outnumbered girls but this preponderance was especially pronounced in congGHD patients (male:female=4:1) with a central malformation that associates an anterior pituitary hypoplasia, a missing, fine or normal pituitary stalk and an ectopic posterior pituitary. Thirteen percent of the patients with idGHD, 50% with congGHD and 52% with acqGHD had multiple pituitary deficiencies. Patients with congGHD were the youngest (mean+/-s.d. age: 6.5+/-4.7 years) and were the shortest (-3.0+/-1.3 standard deviation score (SDS)) at the start of rhGH treatment. There was no time trend over the studied period for age and height at onset of GH therapy. CONCLUSION: In Belgium, the prevalence of childhood GHD can be estimated as 1/5600 which is comparable to other recent surveys. The yearly number of new patients for the different aetiologies and the auxological parameters have remained relatively constant over the last 16 years.
Published: 2004

37. Final height in children with idiopathic growth hormone deficiency treated with recombinant human growth hormone: the Belgian experience

Author: Mark Vandeweghe, M. V. L. Du Caju, Muriel Thomas, Claudine Heinrichs, Marc Maes, G. Thiry-Counson, Margarita Craen, G Massa, J P Bourguignon, Raoul Rooman, J. De Schepper, L Dooms, Paul Malvaux, F. de Zegher, and Inge Francois
Subjects: Male, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, Birth weight, law.invention, Growth hormone deficiency, Endocrinology, Belgium, law, Internal medicine, Turner syndrome, otorhinolaryngologic diseases, Medicine, Idiopathic growth hormone deficiency, Birth Weight, Humans, Child, business.industry, Human Growth Hormone, Human growth hormone, Final height, Puberty, medicine.disease, Body Height, Growth hormone treatment, Pediatrics, Perinatology and Child Health, Recombinant DNA, Female, business
Abstract: Background: The growth response to recombinant hGH (rhGH) treatment and final height of 61 Belgian children (32 boys) with idiopathic growth hormone deficiency (GHD) were studied. Patients/Methods: Two patient groups were compared: Group 1 with spontaneous puberty (n = 49), Group 2 with induced puberty (n = 12). The patients were treated with daily subcutaneous injections of rhGH in a dose of 0.5–0.7 IU/kg/week (0.17–0.23 mg/kg/week) from the mean ± SD age of 11.9 ± 3.1 years during 5.1 ± 2.1 years. Results: rhGH treatment induced a doubling of the height velocity during the first year and resulted in a normalisation of height in 53 (87%) patients. Final height was –0.7 ± 1.1 SDS, being 170.4 ± 7.2 cm in boys and 158.0 ± 6.4 cm in girls. Corrected for mid-parental height, final height was 0.0 ± 1.1 SDS. Ninety-two percent of the patients attained an adult height within the genetically determined target height range. Although height gain during puberty was smaller in the patients with induced puberty (boys: 17.1 ± 7.0 cm vs. 27.5 ± 6.6 cm (p < 0.005); girls: 9.6 ± 7.4 cm vs. 22.2 ± 6.1 cm (p < 0.005)), no differences in final height after adjustment for mid-parental height were found between patients with spontaneous or induced puberty. Conclusions: We conclude that patients with idiopathic GHD treated with rhGH administered as daily subcutaneous injections in a dose of 0.5–0.7 IU/kg/week reach their genetic growth potential, resulting in a normalisation of height in the majority of them, irrespective of spontaneous or induced puberty.
Published: 2001

38. Growth hormone isoforms in newborns and postpartum women

Author: Barbro Carlsson, F. De Zegher, Lena M. S. Carlsson, Margaret C. S. Boguszewski, and Cesar Luiz Boguszewski
Subjects: Adult, Male, Polycythaemia, medicine.medical_specialty, Time Factors, Somatotropic cell, Endocrinology, Diabetes and Metabolism, Endocrinology, Internal medicine, medicine, Humans, Protein Isoforms, Receptor, Pregnancy, business.industry, Human Growth Hormone, Postpartum Period, Infant, Newborn, General Medicine, medicine.disease, Prolactin, Growth hormone secretion, Arterial blood, Female, business, Postpartum period
Abstract: The neonatal and postpartum periods are characterized by alterations in pituitary GH secretion. We have investigated the proportion of circulating non-22kDa GH isoforms in newborns, in women within the early postpartum phase (just after the disappearance of placental GH from the maternal circulation) and in women during late postpartum (during the somatotroph recovery phase). We studied 10 newborns (7 males; 3 females; median postnatal age, 45h), who had been admitted because of polycythaemia, 10 women in the early postpartum phase (median, 48h after delivery; range, 42-54h), 18 women in the late postpartum phase (median, 10 weeks after delivery; range, 3-25 weeks) and 9 healthy non-pregnant women. The proportion of non-22kDa GH isoforms was determined by the 22kDa GH exclusion assay, which is based on immunomagnetic extraction of 22kDa GH from serum, and quantitation of non-22kDa GH isoforms using a polyclonal GH assay. In newborns, non-22kDa GH isoforms were measured in two arterial blood samples obtained with a 5-6h interval. In the other groups, serum samples were obtained 40min after an i.v. bolus administration of the GH secretagogue, GH releasing peptide-1 (GHRP-1).In newborns, the median proportion of non-22kDa GH isoforms was 10% (range, 7. 2-19.4%) and the values were similar in samples collected at different times. In early postpartum women, total GH levels after GHRP-1 were lower and the proportion of non-22kDa GH isoforms was higher compared with the values in non-pregnant and late-postpartum women. In late postpartum, there was a partial recovery of GH response to GHRP-1, as shown by an increment in total GH levels, which was associated with a decrease in the fraction of non-22kDa GH isoforms. In conclusion, we found that (i) the proportion of non-22kDa GH isoforms in the newborn is comparable to that in the adult (non-pregnant women), (ii) in early postpartum, the non-22kDa fraction is high within the small pool of readily releasable GH, (iii) in late postpartum, recovery of pituitary GH responsiveness is associated with a relative decrease in the release of non-22kDa GH isoforms.
Published: 2000

39. Low-dose flutamide for women with androgen excess: Anti-androgenic efficacy and hepatic safety

Author: Lourdes Ibáñez and F. de Zegher
Subjects: Hirsutism, medicine.medical_specialty, Time Factors, Endocrinology, Diabetes and Metabolism, Androgen Excess, Flutamide, chemistry.chemical_compound, Endocrinology, Internal medicine, medicine, Humans, hirsutism, Acne, business.industry, Hyperandrogenism, Low dose, Androgen Antagonists, Anti androgenic, medicine.disease, chemistry, Androgens, Female, Chemical and Drug Induced Liver Injury, business, Pioglitazone, medicine.drug
Published: 2009
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40. Male pseudohermaphroditism related to complications at conception, in early pregnancy or in prenatal growth

Author: M. van Helvoirt, Inge Francois, and F. de Zegher
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Birth weight, Disorders of Sex Development, Early pregnancy factor, Embryonic and Fetal Development, Endocrinology, Pregnancy, Testis, medicine, Fetal growth, Birth Weight, Humans, Testosterone, Child, Gynecology, Fetus, biology, Obstetrics, business.industry, medicine.disease, Pregnancy Complications, Fertilization, Pediatrics, Perinatology and Child Health, Male pseudohermaphroditism, biology.protein, Female, business
Abstract: We examined whether male pseudohermaphroditism, when unexplained, is associated with reduced prenatal growth. Birth weight SD scores of 29 children with male pseudohermaphroditism were compared. The scores of children with an unexplained condition (median –2.1 SD) were found to be lower (p = 0.0001) than those of children with an explained condition (median –0.4 SD). In the majority of cases of unexplained male pseudohermaphroditism, there was a complicated history before conception or in early pregnancy. In conclusion, hitherto unexplained male pseudohermaphroditism was found to be associated with reduced prenatal growth and complications at conception or in early pregnancy.
Published: 1999

41. Endocrinology and metabolism after premature pubarche in girls

Author: F. de Zegher, L Lbáñez, and Neus Potau
Subjects: medicine.medical_specialty, Puberty, Precocious, Androgen Excess, Anovulation, Sex hormone-binding globulin, Internal medicine, medicine, Birth Weight, Humans, Insulin-Like Growth Factor I, Child, biology, business.industry, Ovary, Hyperandrogenism, General Medicine, medicine.disease, Pubic hair, Low birth weight, Endocrinology, medicine.anatomical_structure, Pediatrics, Perinatology and Child Health, biology.protein, Female, Insulin Resistance, medicine.symptom, business, Hyperinsulinism, Polycystic Ovary Syndrome, Hormone
Abstract: The prevalence of functional ovarian hyperandrogenism, hyperinsulinism and dyslipidaemia is increased in adolescent girls with a history of premature pubarche, defined as the appearance of pubic hair before the age of 8 years. The ovarian hyperandrogenism is characterized by clinical signs of androgen excess and an exaggerated ovarian 17-hydroxyprogesterone response to gonadotrophin-releasing hormone agonist stimulation. The hyperinsulinism and dyslipidaemia are detectable before and during pubertal development, and they are commonly accompanied by low serum levels of insulin-like growth factor binding protein-1 (IGFBP-1) and sex hormone binding globulin, and by an increased prevalence of anovulation from late adolescence onwards. In girls, premature pubarche, hyperinsulinism, low serum levels of IGFBP-1, dyslipidaemia, anovulation and hyperandrogenism (or various combinations of these conditions) have been related to reduced fetal growth, indicating that these constellations or sequences may have a prenatal origin. These findings suggest that premature pubarche in girls should no longer be regarded as merely a normal variant of development, but rather as a childhood marker pointing to an increased risk of a polyendocrine-metabolic disorder of prenatal origin.
Published: 1999

42. Empty sella, growth hormone deficiency and pseudotumour cerebri: effect of initiation, withdrawal and resumption of growth hormone therapy

Author: J. Silberstein, Inge Francois, Ingele Casteels, Paul Casaer, and F. de Zegher
Subjects: Male, medicine.medical_specialty, Pseudotumor cerebri, medicine.medical_treatment, Growth hormone, Empty sella syndrome, Growth hormone deficiency, Central nervous system disease, Internal medicine, medicine, Humans, Child, Growth Disorders, Chemotherapy, Pseudotumor Cerebri, business.industry, Empty Sella Syndrome, medicine.disease, eye diseases, Endocrinology, Growth Hormone, Pediatrics, Perinatology and Child Health, Diabetes insipidus, Complication, business, Diabetes Insipidus
Abstract: An 11- year-old boy with normal visus and eye fundus, but with empty sella, growth hormone (GH) deficiency and central diabetes insipidus was found to have intracranial hypertension with papilloedema after 6 months of catch-up growth under recombinant human GH (rhGH) replacement therapy. Withdrawal of rhGH therapy was associated with normalisation of intra‐cranial␣pressure within 1 week. Three months later, resumption of rhGH therapy at a lower dose was again followed by pronounced growth acceleration, but now without papilloedema. Conclusion Children with empty sella and GH deficiency may be prone to rhGH-induced pseudotumour cerebri which appears to be rapidly reversible and dose-dependent.
Published: 1997

43. Growth hormone secretion and sensitivity in children born small for gestational age

Author: Bernard L. Salle, M Tauber, F. de Zegher, Olivier Claris, J L Chaussain, M C Cauderay, and Pierre Chatelain
Subjects: medicine.medical_specialty, business.industry, Human Growth Hormone, Infant, Newborn, Gestational age, General Medicine, Growth, medicine.disease, Growth hormone, Growth hormone secretion, Low birth weight, Endocrinology, Internal medicine, Pediatrics, Perinatology and Child Health, Infant, Small for Gestational Age, medicine, Small for gestational age, Humans, Secretion, Female, medicine.symptom, business, Child, reproductive and urinary physiology
Abstract: This short communication discusses aspects of growth hormone (GH) secretion and GH insensitivity in short children born short for gestational age (SGA).
Published: 1996

44. Growth hormone treatment of short children born small for gestational age: metanalysis of four independent, randomized, controlled, multicentre studies

Author: O. Butenandt, Kerstin Albertsson-Wikland, Patrick Wilton, F. de Zegher, Pierre Chatelain, J L Chaussain, Björn Jonsson, and Annika Löfström
Subjects: medicine.medical_specialty, Growth, Short stature, Body Mass Index, Internal medicine, Age Determination by Skeleton, medicine, Humans, Multicenter Studies as Topic, Child, Randomized Controlled Trials as Topic, Fetus, business.industry, Body Weight, Infant, Newborn, Bone age, General Medicine, medicine.disease, Body Height, Growth hormone treatment, Endocrinology, Child, Preschool, Growth Hormone, Pediatrics, Perinatology and Child Health, Infant, Small for Gestational Age, Bone maturation, Small for gestational age, medicine.symptom, business, Weight gain, Body mass index
Abstract: A minority of children born small for gestational age (SGA) fail to achieve sufficient catch-up growth during infancy and remain short throughout childhood, apparently without being growth hormone (GH) deficient. The effect of GH administration was evaluated over 2 years in short prepubertal children born SGA. The children (n = 244), who were taking part in four independent multicentre studies, had been randomly allocated to groups receiving either no treatment or GH treatment at a daily dose of 0.1, 0.2 or 0.3 IU/kg (0.033, 0.067 or 0.1 mg/kg) s.c. At birth, their mean length SD score (SDS) was -3.6 and their mean weight SDS -2.6; at the start of the study, mean age was 5.2 years, bone age 3.8 years, height SDS -3.3, height SDS adjusted for parental height -2.4, weight SDS -4.7 and body mass index (BMI) SDS -1.4. The untreated children had a low-normal growth velocity and poor weight gain. Although bone maturation progressed more slowly than chronological age, final height prognosis tended to decrease, according to height SDS for bone age, GH treatment induced a dose-dependent effect on growth, up to a near doubling of height velocity and weight gain; BMI SDS was not altered. Bone maturation was also accelerated differentially; however, final height prognosis increased in all GH treatment groups. The more pronounced growth responses were observed in younger children with a lower height and weight SDS. In conclusion, GH administration is a promising therapy for normalizing short stature and low weight after insufficient catch-up growth in children born SGA. Long-term strategies incorporating GH therapy now remain to be established.
Published: 1996

45. Association of hyperprolinaemia type I and heparin cofactor II deficiency with CATCH 22 syndrome: evidence for a contiguous gene syndrome locating the proline oxidase gene

Author: Inge Francois, Jaak Jaeken, Jean-Pierre Fryns, Nathalie Goemans, and F. de Zegher
Subjects: medicine.medical_specialty, Adolescent, Proline, Chromosomes, Human, Pair 22, In situ hybridization, Biology, Contiguous gene syndrome, Internal medicine, Genetics, medicine, Proline Oxidase, Humans, Abnormalities, Multiple, Genetics (clinical), Heparin cofactor II, Oxidase test, Proline oxidase, Psychomotor retardation, Syndrome, medicine.disease, Endocrinology, Hyperprolinemia, Heparin Cofactor II, Female, medicine.symptom, Gene Deletion
Abstract: Increased proline levels were found in plasma of a girl with slight psychomotor retardation, epilepsy, obesity, scoliosis, hypocalcaemia, variable lymphocytopenia and facial dysmorphy suggestive of CATCH 22 syndrome. Fluorescence in situ hybridization indicated the presence of a submicroscopic 22q11 deletion, confirming this diagnosis. Further investigation showed evidence that the patient was heterozygous for heparin cofactor II deficiency and for hyperprolinaemia type I, a proline catabolic disorder due to proline oxidase deficiency. This association extends the CATCH 22 syndrome and suggests that expression of the proline oxidase gene depends on the chromosome 22q11 region.
Published: 1996

46. The prenatal role of thyroid hormone evidenced by fetomaternal Pit-1 deficiency

Author: Christine Vanhole, F. Pernasetti, F. de Zegher, Hugo Devlieger, Joseph Martial, and G Van den Berghe
Subjects: Adult, medicine.medical_specialty, Heterozygote, Thyroid Hormones, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Biology, Biochemistry, Endocrinology, Fetus, Thyrotropic cell, Pregnancy, Internal medicine, medicine, Humans, Point Mutation, Homeodomain Proteins, Biochemistry (medical), Thyroid, Skull, Infant, Newborn, medicine.disease, Congenital hypothyroidism, DNA-Binding Proteins, Pregnancy Complications, Fetal Diseases, Fetal circulation, medicine.anatomical_structure, Genes, Bone maturation, Female, Radiography, Thoracic, Transcription Factor Pit-1, Hormone, Transcription Factors
Abstract: The role of thyroid hormone in the human fetus is uncertain; a significant amount of T4 is transferred from the maternal to the fetal circulation. A mother-infant pair was found to be heterozygotic for a point mutation in codon 271 of the gene encoding Pit-1, a pituitary-specific transcription factor regulating somatotrope, lactotrope, and thyrotrope function. At birth, serum T4 was undetectable in mother and infant. The newborn presented with a striking delay of respiratory, cardiovascular, neurological, and bone maturation. Despite replacement therapy since birth, neurological development of the infant is impaired. Fetomaternal Pit-1 deficiency resulted in unmitigated fetal hypothyroidism that unmasked thyroid hormone as a potent endogenous drive of fetal maturation and revealed placental transfer of maternal T4 as a rescue mechanism for infants with congenital hypothyroidism, preventing fetal and neonatal symptoms of thyroid deficiency and safeguarding developmental potential.
Published: 1995

47. The foetal pituitary, postmaturity and breech presentation

Author: I Francois, G Van den Berghe, F. de Zegher, C Vanhole, H Devlieger, SL Kaplan, and Melvin M. Grumbach
Subjects: Gynecology, Anterior hypopituitarism, Male, medicine.medical_specialty, Pituitary gland, Hypothalamic Hormones, business.industry, Infant, Newborn, General Medicine, Hypopituitarism, medicine.disease, Infant newborn, Infant, Postmature, Fetal Diseases, medicine.anatomical_structure, Breech presentation, Pregnancy, Pituitary Gland, Pediatrics, Perinatology and Child Health, Medicine, Humans, Female, business, Breech Presentation
Published: 1995

48. Growth hormone deficiency and premature thelarche in a female infant with kabuki makeup syndrome

Author: Koenraad Devriendt, L. Lemli, M. Craen, and F. de Zegher
Subjects: medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Pituitary Diseases, Kabuki, Hypothalamic disease, Short stature, Growth hormone deficiency, Growth velocity, Endocrinology, Premature thelarche, Internal medicine, medicine, Humans, Abnormalities, Multiple, Breast, business.industry, Infant, Newborn, Syndrome, medicine.disease, Recombinant Proteins, Growth hormone treatment, Partial growth hormone deficiency, Growth Hormone, Female, medicine.symptom, business, Hypothalamic Diseases
Abstract: We report on a girl with the kabuki makeup syndrome, including short stature, premature thelarche and partial growth hormone deficiency of hypothalamic origin, without stalk interruption. Treatment with recombinant human growth hormone resulted in an increase of annualized growth velocity from 3.6 to 11.2 cm. The kabuki makeup syndrome may be associated with hypothalamopituitary dysfunction.
Published: 1995

49. Asplenia syndrome and isolated total anomalous pulmonary venous connection in siblings

Author: F. de Zegher, A. Casaer, Monique Dumoulin, A. Van Cauter, Marc Gewillig, Koenraad Devriendt, and Hugo Devlieger
Subjects: Heart Defects, Congenital, Male, medicine.medical_specialty, Heart disease, Internal medicine, Medicine, Humans, Sibling, Total anomalous pulmonary venous connection, Lung, business.industry, Genetic disorder, Infant, Newborn, Infant, Syndrome, medicine.disease, Situs Inversus, Surgery, Pedigree, Situs inversus, medicine.anatomical_structure, Pediatrics, Perinatology and Child Health, Cardiology, Polysplenia, Splenic disease, business, Spleen
Abstract: We report on a family with asplenia syndrome in one and total anomalous pulmonary venous connection (TAPVC) in the other sib. Both conditions are rare, may have a genetic cause and belong to a spectrum of laterality disorders. This suggests that both asplenia syndrome and TAPVC in this family are the clinical expression of a single genetic disorder.
Published: 1994

50. Opposite effects of growth hormone and estrogens on the pregnancy zone protein serum levels in children and adolescents

Author: J J Cassiman, Magda Vanderschueren-Lodeweyckx, F. de Zegher, Koenraad Devriendt, Guy Massa, H. Van Den Berghe, and Peter Marynen
Subjects: Adult, Male, medicine.medical_specialty, Gonad, Adolescent, medicine.drug_class, Endocrinology, Diabetes and Metabolism, Down-Regulation, Turner Syndrome, Biology, Pregnancy Proteins, Growth hormone deficiency, Endocrinology, Pregnancy, Internal medicine, Ethinylestradiol, Turner syndrome, medicine, Humans, Child, Dwarfism, Pituitary, Analysis of Variance, Estradiol, Puberty, General Medicine, medicine.disease, Recombinant Proteins, PREGNANCY ZONE PROTEIN, Growth hormone treatment, Pregnancy Complications, medicine.anatomical_structure, Estrogen, Growth Hormone, Female, medicine.drug, Follow-Up Studies
Abstract: Serum levels of pregnancy zone protein were measured in children with growth hormone deficiency and in girls with Turner syndrome, before and during treatment with recombinant human growth hormone and in healthy controls. The pregnancy zone protein serum levels in growth hormone deficiency patients before treatment were significantly higher than in controls (median value 2420 μg/l vs 434 μg/l; p≤0.001). In Turner syndrome patients they were within the normal range. The administration of rhGH to both growth hormone deficiency and Turner syndrome patients resulted in a significant decrease in the serum pregnancy zone protein levels by approximately 50%. The addition of 50 ng·kg−1·d −1 ethinylestradiol to the growth hormone treatment in Turner syndrome patients led to an increase in pregnancy zone protein concentrations in four out of five patients. Elevated pregnancy zone protein levels were also found in two children with growth hormone resistance (Laron type dwarfism). In one patient with placental growth hormone deficiency, pregnancy zone protein serum levels during pregnancy were within the normal range. These results suggest that the serum pregnancy zone protein levels are down-regulated by growth hormone.
Published: 1993

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