bluuebunny/crossref_metadata_2025 huggingface dataset:
Urinary Lactic Dehydrogenase Isoenzyme Analysis in Children with Spinal Lesions
Authors: YOKOCHI K. , UCHIDA T. , KODAMA K.
Published: April 2008

ABSTRACT. In 48 children with spinal lesions and micturition problems urinary lactic dehydrogenase (LDH) isoenzymes were analyzed. They had higher total LDH activities (716.8 ± 1050.2 nkat/1), isoenzymes V percents (22.2 ± 13.0 %) and isoenzyme V activities (203.4 ± 308.4 nkat/l) than those of healthy children (150.0 ± 83.4 nkat/1,1.9 ± 1.0 %, 5.0 ± 3.3 nkat/1). Many subjects had an isoenzyme V‐dominant LDH isoenzyme pattern. Among 48 subjects the patients with pyuria, bacteriuria or abnormal pyelograms had markedly high total LDH activities, isoenzyme V percents and isoenzyme V activities. The rise in LDH isoenzyme V levels may reflect the renal damage in the patients with neurogenic bladders.
Risk of Progressive Kidney Damage after Acute Leukemia
Authors: HOVI L. , KOSKIMIES O. , HOLMBERG C. , RAJANTIE J. , RAUTONEN J. , SIIMES M. A.
Published: April 2008

ABSTRACT. In order to evaluate potential long‐term renal sequelae of childhood leukemia, we studied 62 consecutive patients successfully treated for acute leukemia in 1971–83. At the time of this follow‐up study they had been off therapy for 1–9 years and they were all in complete remission. Relative renal length was measured from X‐ray films of intravenous pyelograms. Median relative renal length prior to the start of chemotherapy was + 1.0 SD (range −1.5 to + 4.0, n= 35), at discontinuation of therapy + 0.5 SD (range −1.5 to + 2.2, n= 22), and at follow‐up −0.3 SD (range −3.9 to + 2.6, n= 61). The mean calculated decrease in relative kidney size was 0.1 SD unit per year during the follow‐up time. The median glomerular filtration rate was 110 ml/min/1.73 m2 (range 70 to 164). Six of 60 patients had glomerular filtration rates below 85 ml/min/1.73 m2. Three patients had some evidence of tubular dysfunction documented by increased excretion of urinary amino acids and/or beta‐2‐micro‐globulin or by reduced concentrating capacity. In spite of these abnormalities, we conclude that in most long‐term survivors of childhood leukemia renal size and function are relatively well preserved. However, slightly reduced glomerular filtration rates in some patients indicated renal damage. A longer follow‐up time is needed to find out whether the decrease in relative renal length is still continuing.
Glucose Metabolism and Insulin Secretion in Infants with Symptomatic Ventricular Septal Defect
Authors: LUNDELL K.‐H. , SABEL K.‐G. , ERIKSSON B. O. , MELLGREN G.
Published: April 2008

ABSTRACT. Nineteen infants with symptomatic ventricular septal defect (VSD) were examined on, altogether, 26 occasions, when each was given an intravenous glucose tolerance test (IVGTT); concentrations of insulin‐ and C‐peptide in plasma were determined. Comparisons were made with 14 healthy infants of the same age. The VSD infants were growth retarded with lower weight/age and length/age ratios. Glucose tolerance as indicated by glucose fasting levels and response to intravenous glucose tolerance test, including glucose disappearance rate, did not differ between the two groups. In response to the glucose load, insulin in plasma was significantly less in VSD infants. In response to the IVGTT, insulin secretion rate calculated from C‐peptide levels in plasma was significantly elevated in the VSD group. We conclude that compared to healthy infants, those with symptomatic VSD have normal glucose tolerance, increased secretion rate of insulin, but decreased levels of circulating insulin in response to an intravenous glucose load. We suggest this is so because binding of insulin to peripheral receptors and/or insulin extraction in the liver somehow increases.
Lethal Respiratory Failure in Preterm Infants due to Cystic Fibrosis
Authors: SHARPLES P. M. , COLDITZ P. B. , WILKINSON A. R.
Published: April 2008

ABSTRACT. We present the first report of two preterm infants who died from respiratory failure secondary to cystic fibrosis which presented in the early neonatal period.
Crohn's Disease Penetrating into the Spinal Canal
Authors: SACHER M. , GOPFRICH H. , HOCHBERGER O.
Published: April 2008

ABSTRACT. An 11‐year‐old boy who had suffered from Crohn's disease of the large bowel for 4 years developed high fever, severe back pain and flexion‐contracture of the right hip joint with inability to walk. After several weeks radicular irritation also became apparent. CT‐scan demonstrated an abscess of the right psoas muscle that had also infiltrated the spinal canal, leading to a spinal extradural abscess extending from L2‐S4. Therapy comprised surgical drainage of the psoas abscess and conservative therapy (mainly steroids and hypercaloric diet) and resulted in complete cure of the psoas and the spinal abscess. Spinal infiltration is a rare and serious complication of Crohn's disease and must be considered in every case of significant back pain with or without obvious neurological signs.
BOOK REVIEW
Authors: Kyllerman Mårten
Published: April 2008

book review in this article:

E. M. R. Critchley, Neurological emergencies. Major problems in neurology, vol. 17. W. Saunders Company, London 1988, 502 pages.
The transition from fetus to neonate – an endocrine perspective
Authors: Gluckman PD , Sizonenko SV , Bassett NS
Published: April 2008

Gluckman PD, Sizonenko SV, Bassett NS. The transition from fetus to neonate ‐ an endocrine perspective. Acta Pædiatr 1999; Suppl 428: 7–11. Stockholm. ISSN 0803–5326

The transition from fetus to neonate involves three phases: late gestation, parturition and the processes needed to establish independent homoeostatic regulation after separation from the placenta. These phases are regulated by a series of fetal and placental endocrine events. Glucocorticoids have an important role in the preparation for birth, including involvement in lung and cardiac development, and the maturation of enzymes in a variety of pathways. Fetal Cortisol production is, in turn, also under hormonal control. Parturition is a complex process, which is still poorly understood in humans. The final steps are largely dependent on the effect of prostaglandin F2α on the myometrium associated with increased oxytocin activity. The transition to birth is accompanied by changes in respiration, circulation, glucose homoeostasis, and the onset of independent oral feeding and thermoregulation. Several examples of endocrine components of the transition from fetal to neonatal life are reviewed here: the role of prostanoids, the onset of thermogenesis, and changes in the thyroid hormone and growth hormone axes. The effects of hormone levels on prematurity and growth retardation are also discussed. □Birth transition, fetus, gestation, hormonal control, neonate, parturition
Obesity: a growing problem
Authors: Seidell JC
Published: April 2008

Seidell JC. Obesity: a growing problem. Acta Pædiatr 1999; Suppl 428: 46–50. Stockholm. ISSN 0803–5326

Obesity, defined as a body mass index (BMI) of 30 kg/m2 or more, is common in many parts of the world, especially in the established market economies, the former socialist economies of Europe, Latin America, the Caribbean and the Middle Eastern Crescent. As many as 250 million people worldwide may be obese (7% of the adult population) and two to three times as many may be considered overweight. The prevalence of obesity seems to be increasing in most parts of the world, even where it used to be rare. Increased fatness, measured by a high BMI, a large waist circumference or a high waist/hip circumference ratio, is associated with many chronic diseases as well as with poor physical functioning. Assessments of the prevalence of obesity, and trends in this prevalence over time, are more difficult in children than adults, due to the lack of international criteria for classifying individuals as overweight or obese. The World Health Organization has now recommended the use of BMI‐for‐age percentiles, but the reference curves are still under development. France, The Netherlands, the UK and the USA are among the countries that have reported recent increases in the prevalence of obesity in children and adolescents. Although there are no accurate estimates of the components of energy balance and their changes over time, the available evidence suggests that the trends in obesity rates are related more to a reduction in energy expenditure than to an increase in caloric intake. Prevention of obesity through the promotion of a healthy lifestyle is among the important challenges for the new millennium, and should start in childhood, □Adolescents, children, epidemiology, obesity, overweight
Leptin and the genetics of obesity
Authors: Clément K
Published: April 2008

Clément K. Leptin and the genetics of obesity. Acta Pædiatr 1999; Suppl 428: 51–7. Stockholm. ISSN 0803–5326

The discovery of the Ob gene and its product, leptin, is a good example of the contribution made by molecular biology to the understanding of mechanisms initially hypothesized from classic physiological studies. Leptin is produced in adipose tissue and acts on the central nervous system to regulate multiple neuroendocrine secretions. In three rare cases of human morbid obesity, the discovery of mutations in the leptin and leptin receptor genes shows that leptin plays a crucial role in the control of weight and several endocrine functions (particularly reproduction). These studies also illustrate the limits of genetics in the investigation of monogenic forms of animal obesity, and the difficulties of linking molecular findings to the pathophysiology of complex diseases, such as human common obesity. Previous searches for mutations in the leptin and leptin receptor genes indicated that these are probably not major genes for common forms of human obesity. This review focuses on the recent molecular findings that have indicated a putative role for the leptin axis in human obesity. □Adipose tissue, genetics, leptin, leptin receptor, obesity
Final height in idiopathic growth hormone deficiency: the KIGS experience
Authors: Cutfield W , Lindberg A , Wikland K Albertsson , Chatelain P , Ranke MB , Wilton P
Published: April 2008

Cutfield W, Lindberg A, Albertsson Wikland K, Chatelain P, Ranke MB, Wilton P, on behalf of the KIGS International Board. Final height in idiopathic growth hormone deficiency: the KIGS experience. Acta Pædiatr 1999; Suppl 428: 72–5. Stockholm. ISSN 0803–5326

Final height was evaluated in 369 patients with idiopathic growth hormone deficiency (IGHD) enrolled in KIGS ‐ the Pharmacia & Upjohn International Growth Database. At the start of growth hormone (GH) therapy, the patients were 9.8 years of age, their mid‐parental height SDS was ‐0.8, and their height SDS was ‐3.1. Of the 369 patients, 50% had multiple hormone deficiencies, and puberty was induced in 31%. Patients were 18 years of age at completion of GH therapy, and had received GH at a dose of 0.49 IU/kg/week (0.16 mg/kg/week), with a mean of 5.2 injections/week for 8.1 years. Final height SDS was ‐1.5, final minus initial height SDS was 1.7 and final minus mid‐parental height SDS was ‐0.5. A Swedish subgroup (n= 69) received conventional GH therapy throughout at 0.65 IU/kg/week (0.22 mg/kg/week), with seven injections/week for a mean of 9.4 years. These patients achieved their genetic potential (final minus mid‐parental height SDS, 0.03), with a normal final height SDS of ‐0.3. For the total group, the following variables were associated with final height: mid‐parental height SDS (r= 0.62), injection frequency (r= 0.37), duration of GH treatment (r= 0.28), peak stimulated GH concentration (r= ‐0.25), age (r= ‐0.19) (all p < 0.001) and height velocity SDS in the first year of treatment (r= 0.20, p= 0.004). In conclusion, genetic potential, expressed as the mid‐parental height, is the variable with the greatest identified influence on final height during GH treatment in IGHD. Current GH regimens will lead to a normal height and attainment of mid‐parental height. However, higher dose, individualized GH regimens are likely to be necessary for patients with IGHD who are disadvantaged at the time of commencing GH therapy, such as those with short parents, those whose treatment began in late childhood or adolescence and those with less severe GHD. □Final height, growth hormone treatment, height, idiopathic growth hormone deficiency, KIGS
Effect of growth hormone (GH) during puberty in GH‐deficient children: preliminary results from an ongoing randomized trial with different dose regimens
Authors: Wikland K Albertsson , Alm F , Aronsson S , Gustafsson J , Hagenäs L , Häger A , Ivarsson S , Kriström B , Marcus C , Moëll C , Nilsson KO , Ritzén M , Tuvemo T , Westgren U , Westphal O , Åman J
Published: April 2008

Albertsson Wikland K, Alm F, Aronsson S, Gustafsson J, Hagenas L, Hager A, Ivarsson S, Kristrom B, Marcus C, Moe11 C, Nilsson KO, RitzCn M, Tuvemo T, Westgren U, Westphal 0, Aman J. Effect of growth hormone (GH) during puberty in GH‐deficient children: preliminary results from an ongoing randomized trial with different dose regimens. Acta Pxdiatr 1999; Suppl 428:80‐4. Stockholm. ISSN 0803‐5326

This paper reports results from an ongoing, randomized, multicentre national trial. The aim is to elucidate whether a dose of growth hormone (GH) of 0.2 IUkg (0.07 mgkg), given either as once‐daily or twice‐daily injections during puberty, is more effective than a once‐daily dose of 0.1 IU/kg/day (0.03 mg/kg/day) in improving final height in children with GH deficiency (GHD). The twice‐daily regimen comes closer to the spontaneous GH secretion pattern in puberty. Ninety‐two children with GHD who had been receiving GH therapy for at least 1 year, and with spontaneous puberty or who were prepubertal and due to be started on replacement therapy to induce puberty, were randomly assigned to receive GH as follows: group A, 0.1 IU/kg/day (0.03 mg/kg/day), administered once daily; group B, 0.2 IU/kg/day (0.07 mg/kg/day), administered once daily; and group C, 0.2 IUkg/day (0.07 mg/kg/day), divided into two equal injections given at 12‐hour intervals. Pubertal height gain was 0.7, 0.7 and 1.3 SDS for groups A, B and C, respectively. The gain in height during puberty was thus most marked in group C. Mean final height, when corrected for parental height, was between 0 and 1 SDS in all treatment groups. All but seven children reached a final height within 2 SD of the general population. There was a wide range of final heights in all three treatment groups. This variation in response suggests the need to individualize treatment in order to achieve an appropriate final height for most individuals. □Dose, final height, growth hormone treatment, puberty, randomized treatment trial
Growth in Crohn's disease
Authors: Savage MO , Beattie RM , Camacho‐Hübner C , Walker‐Smith JA , Sanderson IR
Published: April 2008

Savage MO, Beattie RM, Camacho‐Hubner C, Walker‐Smith JA, Sanderson IR. Growth in Crohn's disease. Acta Paediatr 1999; Suppl 428:89‐92. Stockholm. ISSN 0803‐5326

Abnormal linear growth is frequent in children and adolescents with Crohn's disease. The typical pattern is of growth retardation associated with delayed skeletal maturation. Puberty is also frequently delayed. Over 50% of patients may have a subnormal height velocity, and approximately 25% will have short stature. The endocrine status is characterized by normal growth hormone secretion and a slightly subnormal serum level of insulin‐like growth factor I, which is related to nutritional status. Principal therapeutic options are intestinal resection for localized disease, and enteral nutrition ‐ using a polymeric diet ‐ for more widespread disease, particularly involving the small intestine. Growth responses to both modalities are often excellent and produce considerable psychological benefit. Optimum therapy is achieved by close collaboration between gastroenterologists and endocrinologists, and by the use of auxologicalmethods to document pre‐ and post‐therapeutic management. □Crohn 's disease, enteral nutrition, growth, intestinal resection, puberty
Growth retardation in chronic diseases: possible mechanisms
Authors: Underwood LE
Published: April 2008

Underwood LE. Growth retardation in chronic diseases: possible mechanisms. Acta Pædiatr 1999; Suppl 428: 93–6. Stockholm. ISSN 0803–5326

Multiple and complex mechanisms are likely to be involved in producing the growth retardation that occurs in children with chronic disease. The principal mechanisms in the pathway leading to growth arrest include too little substrate available to the child, excessive need for and over‐consumption of substrate, and inefficient management of body components needed for growth. It is proposed that alterations in the growth hormone (GH)‐insulin‐like growth factor (IGF) system play a major role at each of the steps between insult from chronic disease and growth retardation. When substrate is insufficient, the production and action of IGF‐I are attenuated at multiple points in the GH‐IGF cascade. When over‐consumption of substrate occurs, a situation of‘internal starvation’probably develops ‐ leading to events similar to those that take place when substrate supply is inadequate. Finally, conditions that cause inefficient management of body components needed for growth, as characterized by increased proteolysis, appear to be attenuated by GH and IGF‐I. □Chronic disease, growth hormone, growth retardation, insulin‐like growth factor I
Growth hormone treatment of short stature and metabolic dysfunction in juvenile chronic arthritis
Authors: Simon D , Touati G , Prieur AM , Ruiz JC , Czernichow P
Published: April 2008

Simon D, Touati G, Prieur AM, Ruiz JC, Czernichow P. Growth hormone treatment of short stature and metabolic dysfunction in juvenile chronic arthritis. Acta Pædiatr 1999; Suppl 428: 100–5. Stockholm. ISSN 0803–5326

Severe growth retardation and profoundly altered body composition are observed in children treated with glucocorticoids for systemic forms of juvenile chronic arthritis. The aim of this study was to assess the effects of 1 year of treatment with growth hormone (GH) on height velocity and body composition, and the potential effects of such treatment on glucose tolerance. Fourteen children receiving steroid therapy for juvenile chronic arthritis were treated with GH, 1.4 IU/kg/week (0.47 mg/kg/week), for 1 year and were then followed up for 1 year after cessation of treatment. Baseline GH secretion and plasma levels of insulin‐like growth factor I (IGF‐I) and IGF‐binding protein‐3 (IGFBP‐3) were at the lower limit of normal, but increased with GH treatment. During the year of GH treatment, mean height velocity increased from 1.9 to 5.4 cm/year (p < 0.001), mean lean body mass increased by 12% (p < 0.01) and mean fat mass fell by 20% (p < 0.01) compared with baseline. Decreased glucose tolerance and increased glycosylated haemoglobin levels were also observed. This may have been a result of insulin resistance, as indicated by induced hyperinsulinaemia. Following the 1‐year GH treatment period, height velocity fell to pretreatment values, and the height SDS at the end of the second year was lower (p 0.01) than before treatment. Weight and fat mass increased markedly after cessation of GH treatment. These results suggest that GH may partially counteract the adverse effects of glucocorticoids on growth and metabolism in patients with chronic inflammatory disease. Long‐term controlled studies are needed to determine the risks and benefits of GH therapy in such patients. □Body composition, growth hormone, juvenile chronic (rheumatoid) arthritis, steroid therapy
Health‐related quality of life in intersexuality
Authors: Meyer‐Bahlburg HFL
Published: April 2008

Meyer‐Bahlburg HFL. Health‐related quality of life in intersexuality. Acta Pædiatr 1999; Suppl 428: 114–15. Stockholm. ISSN 0803–5326

Standardized methods for the assessment of health‐related quality of life in patients with intersexuality are yet to be developed. This paper makes recommendations as to the kind of measures that should be included. □Gender role/identity, health‐related quality of life, intersexuality, sexuality
Growth hormone therapy in hypochondroplasia
Authors: Ramaswami U , Hindmarsh PC , Brook CGD
Published: April 2008

Ramaswami U, Hindmarsh PC, Brook CGD. Growth hormone therapy in hypochondroplasia. Acta Pædiatr 1999; Suppl 428: 116–17. Stockholm. ISSN 0803–5326

Patients with hypochondroplasia present with variable phenotypes. Children with severe short stature and disproportion of the body segments usually have the mutation Asn540Lys. They respond to growth hormone (GH) therapy with an increase in spinal length and, coupled with a surgical leg‐lengthening procedure, it is possible for some patients to achieve adult heights within the normal range. Some children who present with proportionate short stature and hypochondroplasia fail to increase their growth rate at puberty, although the growth spurt can be restored by GH therapy. Others, with an identical presentation, seem to grow normally during puberty. At present, there is no way of predicting who will undergo a normal pubertal growth spurt. We therefore monitor all patients during childhood and give GH treatment only to those patients who fail to develop a growth spurt at puberty. Severe cases may occasionally need treatment before puberty if their growth velocity is compromised, but these will probably also be candidates for a surgical leg‐lengthening procedure. □Growth, growth hormone therapy, hypochondroplasia, puberty, short stature
Molecular defects in achondroplasia and the effects of growth hormone treatment
Authors: Seino Y , Moriwake T , Tanaka H , Inoue M , Kanzaki S , Tanaka T , Matsuo N , Niimi H
Published: April 2008

Seino Y, Moriwake T, Tanaka H, Inoue M, Kanzaki S, Tanaka T, Matsuo N, Niimi H. Molecular defects in achondroplasia and the effects of growth hormone treatment. Acta Pa; diatr 1999; Suppl 428: 118–20. Stockholm. ISSN 0803–5326

Achondroplasia is a common skeletal dysplasia with severe growth retardation. Recently, mutations in the fibroblast growth factor receptor 3 (FGFR3) were identified in patients with achondroplasia. In the present study, 70 of 75 Japanese patients with achondroplasia were found to have a G1138A mutation in FGFR3, and two patients had a G1138C mutation. Growth hormone therapy was given to 145 patients with achondroplasia. Significant dose‐dependent effects on skeletal growth were obtained, with no long‐term adverse effects. □Achondroplasia, fibroblast growth factor receptor, growth hormone therapy, growth, skeletal dysplasia
Natural history of growth hormone receptor deficiency
Authors: Rosenbloom AL , Martinez V , Kranzier JH , Bachrach LK , Rosenfeld RG , Guevara‐Aguirre J
Published: April 2008

Rosenbloom AL, Martinez V, Kranzier JH, Bachrach LK, Rosenfeld RG, Guevara‐Aguirre J. Natural history of growth hormone receptor deficiency. Acta Pædiatr 1999; Suppl 428: 153–6. Stockholm. ISSN 0803–5326

This review discusses the natural history of growth hormone receptor deficiency (GHRD) in relation to epidemiology, mortality, growth, certain aspects of body composition, and intellectual development. The majority of affected individuals are of Semitic origin and 90% come from the Indian peninsula, the Middle East, or elsewhere in the Mediterranean. There is a twofold increased mortality before the age of 7 years for children with GHRD. Affected adults may have increased cardiovascular risk resulting from increased total cholesterol and low‐density lipoprotein cholesterol, unrelated to adiposity or insulin resistance. Intrauterine growth is affected minimally, if at all. Within a genetically homogeneous population in Ecuador, postnatal growth effects are as variable as in a large genetically heterogeneous population. There is no influence of parental heights. Areal bone mineral density is reduced in adults with GHRD, but estimated volumetric bone density (bone mineral apparent density) is normal. Intellectual development is unaffected by GHRD. □Body composition, growth, growth hormone receptor deficiency, insulinlike growth factor I deficiency, intellectual development, Laron syndrome, natural history
New growth hormone receptor exon 9 mutation causes genetic short stature
Authors: Ayling RM , Ross RJM , Towner P , Laue S Von , Finidori J , Moutoussamy S , Buchanan CR , Clayton PE , Norman MR
Published: April 2008

Ayling RM, Ross RJM, Towner P, Von Laue S, Finidori J, Moutoussamy S, Buchanan CR, Clayton PE, Norman MR. Acta Pa; diatr 1999; Suppl 428: 168–72. Stockholm. ISSN 0803–5326.

A novel form of congenital growth hormone insensitivity syndrome (GHIS), which lacks the classic phenotype associated with this condition, is described. Dominant inheritance is shown to result from a heterozygous 876–1 G to C transversion of the 3′ splice acceptor site preceding exon 9 in the growth hormone receptor (GHR) gene. The result of this mutation is a severely truncated cytoplasmic domain of the GHR, which is incapable of transmitting a signal. The mutant receptor is shown to form a heterodimer with the wild‐type GHR, the activity of which is inhibited in a dominant‐negative manner. □Dominant‐negative mutation, growth hormone receptor
Signal transduction defects in growth hormone insensitivity
Authors: Clayton PE , Freeth JS , Whatmore AJ , Ayling RM , Norman MR , Silva CM
Published: April 2008

Clayton PE, Freeth JS, Whatmore AJ, Ayling RM, Norman MR, Silva CM. Signal transduction defects in growth hormone insensitivity. Acta Pædiatr 1999; Suppl 428: 174–8. Stockholm. ISSN 0803–5326

Growth hormone (GH) insensitivity is a heterogeneous condition that can result from mutations within the GH receptor (GHR) and that can be inherited as both an autosomal recessive and a dominant trait. However, evidence from a small number of growth hormone binding protein (GHBP)‐positive families indicates that their GH insensitivity is independent of GHR mutations. Two of these families appear to have distinct abnormalities in GH signal transduction. Studies suggest that one family (classic Laron syndrome phenotype; designated family H) have a signalling defect close to the GHR, preventing activation of both the STAT and MAPK pathways, whereas the other family (less marked phenotype; family M) have a defect in activating MAPK but not the STAT pathway. The children studied here are specifically insensitive to GH and their defect must be exclusive to this signalling system. Thus, families with GHBP‐positive GH insensitivity without GHR mutations are likely to be important models in which to study the specificity of GH signal transduction and the relationship between GH insensitive phenotype and signalling defect. □Growth hormone insensitivity, growth hormone receptor, Laron syndrome, mitogen activated protein kinase, signal transducers and activators of transcription
Effects of insulin‐like growth factor I treatment on statural growth, body composition and phenotype of children with growth hormone insentivity syndrome
Authors: Underwood LE , Backelijauw P , Duncan V
Published: April 2008

Underwood LE, Backelijau P, Duncan V, and the GHIS Collaborative Group. Effects of insulinlike growth factor I treatment on statural growth, body composition and phenotype of children with growth hormone insensitivity syndrome. Acta Paediatr 1999; Suppl 428:182‐4. Stockholm. ISSN 0803‐5326

Eight children with growth hormone insensitivity syndrome (GHIS) have been treated with injections of recombinant human insulin‐like growth factor I (rh1GF‐I) for more than 5 years each. After good acceleration of growth in the first year of therapy, the growth rade decreased to an average of 5‐6 cm/year. In general, growth with IGF‐I therapy is less exuberant than that observed with growth hormone (GH) therapy in GH‐deficient children. IGF is well tolerated, though there may be overgrowth of the lymphoid tissues and the kidneys. Bone mineral density is improved by treatment. The benefits of therapy appear to exceed the risks. □ Growth hormone insensitivity syndrome, insulin‐like growth factor I therapy, Laron syndrome
Short‐term increments of insulin‐like growth factor I (IGF‐I) and IGF‐binding protein‐3 predict the growth response to growth hormone (GH) therapy in GH‐sensitive children
Authors: Schwarze CP , Wollmann HA , Binder G , Ranke MB
Published: April 2008

Schwarze CP, Wollmann HA, Binder G, Ranke MB. Short‐term increments of insulin‐like growth factor I (IGF‐I) and IGF‐binding protein‐3 predict the growth response to growth hormone (GH) therapy in GH‐sensitive children. Acta Paediatr 1999; Suppl 428:200‐8. Stockholm. ISSN 0803‐5326

The present study included a cohort of 42 children aged between 1.7 and 15.4 years, who presented with short stature and growth failure. Basal and generated serum levels of insulin‐like growth factor‐I (IGF‐I) and IGF‐binding protein‐3 (IGFBP‐3), measured in an IGF generation test following four or seven daily injections of growth hormone (GH), 0.1 IU/kg (0.033 mg/kg), were analysed in these patients. The growth response to 1 year of GH treatment, 0.6 IU/kg/week (0.2 mg/kg/week), was also investigated. Median height velocity of these patients increased from‐1.6 SDS (range, ‐4.6 to ‐0.3 SDS) to 3.3 SDS (range, ‐0.2 to 7.1 SDS) after 1 year of GH treatment, and median height SDS increased by 0.7 SDS (range, 0.1 to 2.2 SDS). Strong correlations were observed between basal and generated IGF‐I and IGFBP‐3 levels. The increase in IGEBP‐3 levels in response to GH in the generation test was a strong predictor of the growth response to GH therapy. All the patients in the present study could be differentiated from patients with GH insensitivity syndrome (GHIS) using the criteria of a diagnostic scoring system for GHIS. The most valuable parameters were the increases in IGF‐I and IGFBP‐3 levels in the generation test, which excluded 95.2% of the patients from a diagnosis of GHIS. □ Growth hormone treatment, insulin‐like growth factor I, insulin‐like growth factor binding protein‐3, insulin‐like growth factor generation test
Ovarian tissue cryopreservation: a practical option?
Authors: Rutherford AJ , Gosden RG
Published: April 2008

Strategies to preserve fertility in young women undergoing potentially curative chemotherapy for malignant disease have been extremely limited. This limitation stems from the complex physiology of the human oocyte and the difficulties encountered in attempting to cryopreserve both developing and mature oocytes in sufficient quantities. Although in vitro fertilization and embryo cryopreservation can be used in those young women with a partner, this technique is unsuitable for the vast majority of patients and offers only a small chance of a pregnancy. Advances in cryobiology coupled with encouraging results in laboratory animals have prompted research into the storage of ovarian cortical tissue, which in young women is rich in primordial follicles. This tissue can be grafted back into the host, theoretically restoring the possibility of normal fertility. Primordial follicles contain oocytes at their least differentiated stage and appear to be relatively resistant to the combined insults of cryopreservation and the subsequent grafting procedure. Interest in this technique has been fuelled by its successful application in large domestic animals, such that ovarian tissue banking is being rapidly adopted into clinical practice before there is any hard evidence of its efficacy in humans.
Combined pituirary hormone deficency: role of Pit‐1 and Prop‐1
Authors: Pfaffle RW , Blankenstin O , Wüller S , Kentrup H
Published: April 2008

During fetal development of the anterior pituitary gland, a number of sequential processes occur that effect cell differentiation and proliferation. Molecular anlyses have revealed several steps thay are required for pituitry cell line specification and have identified specific factors that control these steps. The gene encoding the pituitary transcription factor 1 (pit‐1) is expressed during differentiation steps that take place quite late in the development of the anterior pituitary gland. Clinically, patients with mutations ofthePITIgene are characterized by severe deficiencies in growth hormone (GH) and prolactin (PRL), and often develop secondary hypothyroidism. A second pituitary transcription factor is known as Prophet of Pit‐1 (Prop‐1), and a mutation of theProp1gene has been detected in Ames dwarf mice. SeveralProp1mutations have been identified that structurally affect the ‘paired‐like’DNA‐binding domain of the Prop‐1 protein molecule. Patients withPROPlmutations show combined pituitary hormone deficiency. These patients exhibiy secondary hypogonadism in addition to the deficiencies of Gh, PRL and thyroid‐stimulating hormone (TSH) also seen in patients withPITImutations. Although all are in the subnormal range, the levels of GH, PRL and TSH in patients withPROP 1mutations are on average, slightly higher than in patients withPITImulations. Some degree of hypocortisolism may necessitate cortisol substitution in patients withPROP1mutations.
The search for the gene for Silver‐Russell syndrome
Authors: Moore GE , Abu‐Amero S , Wakeling E. , Hitchins M , Monk D , Stanier P , Preece M
Published: April 2008

Patients with Silver‐Russell syndrome display intrauterine growth restriction and other dysmorphic features. No single genetic cause for this syndrome has been found, although there are a small number of familial cases and some patients with chromosomal rearragements. Maternal uniparental disomy of chromosome 7 has been found in approximately 7% of patients with Silver‐Russell syndrome. In five of these patients exhibiting maternal uniparental disomy, no common regions of isodisomy were found, thereby ruling out the expression of a recessive allele. It is most likely that one or more imprinted genes are responsible for the phenotype of Silver‐Russell syndrome. Human chromosome 7 demonstrates homology with two imprinted regions on mouse chromosomes 6 and 11, which are equivalent to human chromosome regions 7q32 and 7p11–p13, respectively. We directly analysed the imprinting status of candidate genes from chromosome 7 that mapped to homologous imprinted regions in the mouse and also had a potential role in growth. The candidates were the genes that encode the epidermal growth factor receptor and the insulin‐like growth binding proteins‐1 and ‐3. All three of these candidate genes are localized to chromosome region 7p11–p13. Using intragenic polymorphisms as markers, we found that all three genes showed biallelic expression in different fetal tissues. Therefore, it is unlikely that these candidate genes are directly involved in producing the phenotype of Silver‐Russell syndrome. Other candidates are under analysis, including two newly identified genes that are known to be imprinted.
SHOX gene mutations and deletions in dyschondrosteosis or Leri‐Weill syndrome
Authors: Cormier‐Daire V , Belin V , Cusin V , Viot G , Girlich D , Toutain A , Moncla A , Vekemans M , Merrer M Le , Munnich A
Published: April 2008

Dyschondrosteosis is an autosomal dominant form of mesomelic dysplasia that is often combined with a deformity of the forearms called Madelung deformity. Based on the observation of X‐Y translocations (p22, q12) in patients with dyschondrosteosis, the authors tested the pseudoautosomal region in eight affected families and showed linkage of the dyschondrosteosis gene to a microsatellite DNA marker at the DXYS233 locus (Zmax=6.26 at θ=0). Since the short stature homeobox‐containing gene (SHOX) involved in idiopathic growth retardation and possibly Turner syndrome maps to this region, SHOX was regarded as a strong candidate gene for dyschondrosteosis. This article reports the detection of large‐scale SHOX deletions in seven of the eight families and a nonsense mutation of SHOX in the remaining family affected with dyschondrosteosis. Additional evidence suggests that Langer mesomelic dwarfism results from homozygous mutations at the genetic locus responsible for dyschondrosteosis.
Endocrinology and metabolism after premature pubarche in girls
Authors: Lbáñez L , Potau N , Zegher F De
Published: April 2008

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 aganist 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 (IGEBP‐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 meaely a normal variant of development, but rather as a childhood marker pointing to an increased risk of a polyendocrine‐metabolic disorder of prenatal origin.
Neuroactive neurosteroids: dehydroepiandrosterone (DHEA) and DHEA sulphate
Authors: Baulieu EE
Published: April 2008

Dehydroepiandrosterone (DHEA) and its sulphate ester (DHEAS) are neuroactive and are both imported into the brain from the circulation and produced in the nervous system. These neurosteroids have neurotrophic and excitatiory effets, and further study is needed to delineate their physiological and pathological functions.
Growth hormone, insulin‐like growth factor I and sex hormones: effects on protein and calcium metabolism
Authors: Mauras N
Published: April 2008

The availability of non‐invasive tracer technologies has greatly facilitated the study of the meta‐bolic effects of nutrients and hormones, particularly in children. This brief review examines recent work on the effects of growth hormone (GH), insulin‐like growth factor I (IGF‐I), testosterone and oestrogen on rates of protein synthesis and degradation and lipolysis, as well as on body composition and bone calcium fluxes in young children and adults. GH acts indirectly on whole body protein pools via IGF‐1, but GH appears to act directly on lipolysis. Testosterone stimulates protein synthesis independently of changes in GH concentrations and acts synergistically with GH to enhance whole body metabolism. Oestrogens and androgens both modulate calcium fluxes, enhancing calcium absorption and retention, and thereby underscoring the importance of both groups of hormones in bone calcium metabolism. Further understanding of the physiological role of these hormones during the critical years of adolescence will give us better tools with which to treat disorders of puberty and growth.
Insulin: the other anabolic hormone of puberty
Authors: Caprio S
Published: April 2008

To determine the effect of puberty on isulin action, we used the euglycaemic‐hyperinsulinaemic clamp technique in combination with stable isotopes and indirect calorimetry in lean preadolescents, adolescents and; adults. These studies indicated that the insulin resistance induced by normal puberty alters glucose metabolism but is insufficient to adversely affect insulin‐stimulated protein metabolism or to inhibit lipolysis. Using the hyperglycaemic clamp technique, we evaluated the impact of the insulin resistance on insulin secretion in pre‐adolescents, adolescents and young adults. These studies revealed that the insulin and C‐peptide responses to a standardized intravenous hyperglycaemic stimulus were two‐to threefold greater in adolescents than in preadolescent children and adults. As growth hormone (GH), insulin‐like growth factor 1 (IGF‐1) and insulin levels normally peak during puberty, we examined the influence of insulin on IGF‐1 regulation by measuring basal GH, total and free IGF‐I, and IGF binding protein (IGFBP) levels in lean adolescents and young adults. During the clamp studies, the adolescents exhibited low levels of IGFBP‐1 and ‐2 as well as a reduced insulin‐induced suppression of IGFBP‐1, compared with lean adults. Thus, we postulate that the insulin resistance of puberty induces compensatory hyperinsulinaemia, which in turn suppresses circulating levels of IGFBP‐1, which in turn leads to increased levels of free IGF‐I.
Role of nutrients in the regulation of in vivo protein metabolism in humans
Authors: Darmaun D
Published: April 2008

Nutrients regulate protein metabolism both in an acute fashion and on a long‐term basis. The ingestion of meals is associated with a dramatic switch from an overall catabolic state to a state of net protein anabolism. The acute response of protein metabolism to meal ingestion is mediated, in part, by an increase in insulin secretion, itself a consequence of glucose absorption. Whereas insulin may primarily suppress rates of proteolysis, amino acids are responsible for the stimulation of protein synthesis that follows food intake. In the long run, the effects of nutrition on protein metabolism depend on the energy supply, the source of the energy (carbohydrate versus fat) and dietary protein intake. Finally, specific amino acids, such as glutamine, may play an additional role as protein anabolic agents.
Five years of growth hormone treatment in children with Prader‐Willi syndrome
Authors: Lindgren AC , Ritzén EM ,   collaboration with the Swedish National Growth Hormone Advisory Group
Published: April 2008

The authors have followed 18 prepubertal children (3‐12 years of age) with Prader‐Willi syndrome during 5 years of growth hormone (GH) treatment. Initially, all the children participated in a randomized, controlled GH trial, conducted to assess the effects of GH treatment on growth, body composition and behaviour. GH was administered to group A (n= 9) at a dose of 0.1 IU/kg/day (0.033 mg/kg/day) for 2 years. Group B (n= 9) was untreated for the first year, but the children were given GH at a dose of 0.2 IU/kg/day (0.066 mg/kg/day) during the second year. Thereafter, all children stopped GH treatment for 6 months and were then restarted with GH at a dose of 0.1 IU/kg/day (0.033 mg/kg/day). During the first year of GH treatment, there was a dramatic increase in height SDS in both groups. The attained height percentile was maintained during the continued GH treatment. Five years after the start of GH treatment, mean height SDS is still above average for age. Four children have reached final height, all within ± 2 SD of target height. During the first year GH treatment, body mass index (BMI) SDS decreased significantly from 3.0 to 1.5 SDS in group A and from 2.8 to 1.2 SDS in group B, but it increased again during the 6‐month period without treatment. Following the restart of GH treatment, BMI SDS has stablized at 1.7 SDS for group A and 2.5 SDS for group B. In 16 of 18 patients, fasting insulin, glucose and the A1c fraction of glycosylated haemoglobin remained within normal ranges during 5 years of GH treatment. Following a period of rapid weight gain, two children have developed non‐insulin‐dependent diabetes mellitus. Glucose homeostasis returned to normal when GH treatment was withdrawn. In conclusion, GH treatment has a proven favourable effect on growth and body composition in patients with Prader‐Willi syndrome. Treatment should be individualized, and close surveillance of glucose homeostasis is needed, especially if the patients is severely obese.
Physical effects of growth hormone treatment in children with Prader‐Willi syndrome
Authors: Myers SE , Carrel AL , Whitman BY , Allen DB
Published: April 2008

A randomized, controlled study of 54 children (age, 4‐16 years) with Prader‐Willi syndrome was conducted to assess the potential beneficial effects of growth hormone (GH) treatment. After observation for 6 months, the children were randomized to receive GH at a dose of 3 IU/m2/day (1 mg/m2/day) (n= 35) or no intervention (n= 19). The effects of GH treatment on linear growth, body composition, muscle strength, pulmonary function and resting energy expenditure were assessed. The levels of GH secreted in resonse to clonidine stimulation were universally low, and mean (± SD) insulin‐like growth factor I SDS was ‐1.2 ± 0.8 pretreatment. In children treated for 1 year, mean height velocity SDS significantly increased from ‐1.0 ± 2.5 to 4.6 ± 2.9 (p < 0.0001), mean percentage body fat decreased from 46.3 ± 8.4% to 38.4 ± 10.7% (p < 0.001), mean lean body mass increased from 20.5 ± 6.3 kg to 25.6 ± 4.3 kg (p <0.01) and respiratory muscle function and physical strength imporved. Mean respiratory quotients significantly decreased from 0.81 to 0.77 (p < 0.001); however, resting energy expenditure did not change. Therefore, GH therapy appears to reduce some of the physical disabilities experienced by children with Prader‐Willi syndrome.
Glucose homeostasis in Prader‐Willi syndrome and potential implications of growth hormone therapy
Authors: Zipf WB
Published: April 2008

Diabetes mellitus is becoming a more frequently recognized complication of Prader‐Willi syndrome. It has been reported that as many as 7‐20% of individuals with Prader‐Willi syndrome may develop this complication. Diabetes mellitus adds to the complexity of an already complex treatment program, causes many serious complications that greatly affect the quality of life of these individuals, and can lead to serious morbidity and mortality. Recent studies suggest that growth hormone (GH) might offer significant advantages to individuals with Prader‐Willi syndrome. However, as a known diabetogenic agent, GH might also incrase the propensity to develop diabetes mellitus. For this reason, the characteristics of the diabetes mellitus that develops in individuals with Prader‐Willi syndrome must be studied and fully understood. The initial assumption has been that the diabetes mellitus associated with this syndrome is identical to that seen in obese individuals without Prader‐Willi syndrome, in whom genetic factors and obesity lead to insulin resistance. Severe insulin resistance in turn leads to pancreatic failure and hence the symptom complex of type 2 diabetes mellitus. To determine if this same pattern is present in patients with Prader‐Willi syndrome, we evaluated both obese children and adults with the syndrome. These Patients were compared with obese individuals without Prader‐Willi syndrome matched for age, gender and weight and who had not yet developed diabetes but had equally long‐standing obesity. We compared the glucose and insulin responses of these two groups, using both oral and intravenous glucose challenges. The results demonstrated that individuals with Prader‐Willi syndrome do not show the predicted insulin resistance that is seen in obese children without the syndrome. In fact, the individuals with Prader‐Willi syndrome showed normal or increased insulin sensitivity. These data do not support the hypothesis that the high incidence of diabetes mellitus in patients with Prader‐Willi syndrome is simply the result of obesity and therefore suggest a different aetiology.