GROWTH IN TURNER'S SYNDROME: SPONTANEOUS AND FLUOXYMESTERONE STIMULATED

Abstract. Lenko, H. L., Perheentupa, J. and Söderholm, A. (The Children's Hospital, University of Helsinki, Finland). Growth in Turner's syndrome: spontaneous and fluoxymesterone-stimulated. Acta Paediatr Scand, Suppl. 277: 57, 1979.-Spontaneous growth was analysed in a group of 55 girls with Turner's syndrome and various karyotypes. Their variation in height and its dependence on parental height were similar to that of normal girls. At all ages, the 45, X karyotype was associated with slightly greater mean stature than the other karyotypes together. The bone ages lagged progressively behind from 10 years onwards. Twenty-five patients aged between 9.1 and 17.2 years were given fluoxymesterone, 0.06–0.17 mg/kg daily, for at least 1 year. Their height velocities increased significantly. This brought about a clear psychological benefit. Their final heights were predicted before and after therapy, with a new method based on the spontaneous growth and bone maturation of our patients. The response was individually variable but, on average, the patients gained in predicted height from the therapy. This effect was not lost during a posttreatment year. Abnormal lowering of the voice occurred in patients receiving ≥=0.15 mg/kg fluoxymesterone daily, but never with ≤0.13 mg/kg. No other adverse effects appeared. Thus, fluoxymesterone is useful for promoting growth in girls with Turner's syndrome.     

THE GROWTH OF THE KIDNEYS IN CHILDREN WITH VESICOURETERIC REFLUX

Abstract. In a retrospective study, 69 kidneys with VUR were divided into 2 groups: One group (A) where VUR stopped within 1 year after operation or conservative treatment and a second group (B) where VUR continued for more than 1 year. Group A had somewhat more severe grades of reflux than group B. The number of infections were practically the same in the two groups. The length of the kidneys was measured at the time of diagnosis and compared with the length at the most recent urography after VUR stopped (group A) on average 2 years and 3 months later and with the most recent urography while VUR was still present (group B) on average 1 year and 9 months later. It was found that 85% in group A had increased in absolute length while the figure was 60% in group B. If the relative growth is calculated (the kidneys' length in relationship to L₁ - L₃ distance), 60% in group B had decreased while only 30% in group A had decreased.     

CATCH-UP GROWTH FOLLOWING LONG-TERM ADMINISTRATION OF ESSENTIAL FATTY ACIDS IN A GIRL WITH GROWTH FAILURE AND ESSENTIAL FATTY ACID DEFICIENCY

ABSTRACT. A 10-year-old girl with benign recurrent intrahepatic cholestasis, malabsorption of fat, growth failure (growth rate 1.2 cm/year) and deficiency of essential fatty acids (EFA) is described. Long-term administration of EFA, mainly by cutaneous application of sunflower seed oil, was followed by a remarkable catch-up growth (23.8 cm in 3.5 years) while the serum values for EFA improved. Since no other changes in the therapeutic regimen occurred and other causes of growth failure and subsequent acceleration of growth could be ruled out, it is highly probable that the observed increase in growth rate was the result of the administration of EFA.     

THE EFFECT OF L-DOPA WITH AND WITHOUT DECARBOXYLASE INHIBITOR ON GROWTH HORMONE SECRETION IN CHILDREN WITH SHORT STATURE

Abstract The efficiency of L-dopa alone and L-dopa plus a dopa-decarboxylase inhibitor (carbidopa) in provoking growth hormone (GH) secretion was studied in 40 children with short stature. By preventing the extracerebral metabolism, carbidopa increases the availability of L-dopa to the brain. The study was designed as paired series of growth hormone stimulation tests in which the effect of L-dopa alone, in different dosage schedules, was compared with the same dose level of L-dopa plus carbidopa. When L-dopa was given in full dose (125–500 mg), there was no significant difference in the serum GH concentrations at any time of sampling. In the lower dose level, the stimulant effect of L-dopa alone tended to be exceeded by the combination of L-dopa and carbidopa. The serum GH responses to the different schedules indicate that an optimal hypothalamic dopamine concentration for GH release could be achieved with a considerably lower dose of L-dopa than those employed in previously reported studies. When L-dopa is combined with a dopa decarboxylase inhibitor, the children have the advantage of less side effects in the form of nausea and vomiting.     

LINEAR GROWTH OF CHILDREN WITH LIMB DEFORMITIES FOLLOWING EXPOSURE TO THALIDOMIDE IN UTERO

Abstract. The growth of 202 children exposed to thalidomide in utero and having upper (139 children) or lower (63 children) limb deformities has been assessed towards the end of pre-pubertal growth. The analyses show that children exposed to thalidomide are shorter than normal children but grow at a normal velocity later. These findings may help in consideration of the mechanism by which thalidomide exerted its teratogenic effect. Analyses of growth may find a wider use in the retrospective assessment of drugs which are potentially harmful in pregnancy.     

IMPAIRED DELAYED HYPERSENSITIVITY IN SUBACUTE SCLEROSING PANENCEPHALITIS

Two children with subacute sclerosing pan-encephalitis showed impaired delayed hypersensitive reaction to killed measles virus in the presence of normal response to candida extract, phytohemagglutinin and PPD. These results suggest that the persistence of the virus in the brain may induce tolerance of the T lymphocytes to it and perpetuate the disease.     

CUTIS LAXA ASSOCIATED WITH SEVERE INTRAUTERINE GROWTH RETARDATION AND CONGENITAL DISLOCATION OF THE HIP

Two female siblings with cutis laxa are reported. Both these infants showed marked intrauterine growth retardation, hyperlaxity of the joints, with congenital dislocation of the hip. Four similar female infants have been reported in the literature. The mode of inheritance appears to be as an autosomal recessive gene. The marked degree of intrauterine growth retardation may be indicative of a more severe form of the disease, which might be lethal in the male foetus.     

STUDIES ON GROWTH HORMONE SECRETION IN A PATIENT WITH THE DIENCEPHALIC SYNDROME OF EMACIATION

A girl with a large optic glioma, and the typical features of diencephalic syndrome of emaciation (Russell) was followed up from ¹/₂ to 2 ¹/₂ years of age. She had very high levels of growth hormone (GH) in the plasma, which were not influenced by hyperglycaemia, by hypoglycaemia or by dexamethasone, reserpine or chlorpromazine. Interference by the glioma with GH releasing factor or more likely with GH inhibiting factor is suggested. In spite of the elevated plasma GH, linear growth was markedly retarded. Sulfation factor activity (Somatomedin) was low with no significant response to injections of HGH. The patho-genesis of the profound metabolic disturbances in this syndrome is not properly understood. The endogenous GH obviously exerts its full adipokinetic effect, whereas the synthesis of the sulfation factor (Somatomedin) must be defective. This case illustrates a type of retardation of linear growth, not seen in any other known syndrome.     

GROWTH AND DEVELOPMENT IN A GIRL WITH PSEUDOHYPOPARATHYROIDISM AND HYPOTHYROIDISM

ABSTRACT. Statural growth, physical and skeletal development of a girl with pseudohypoparathyroidism and primary hypothyroidism were analysed in a longitudinal study, which lasted for 12 years from the age of 0.8 years. Growth in height, which slowed down when thyroid therapy was withheld, was within the normal range. Still, as a result of early puberty, the girl became a small adult. Skeletal age was advanced over chronological years by an average of 2.7 years. This rapid skeletal development was more pronounced in the tubular bones than in the round bones of the hand. Two of the five metacarpals of the left hand grew more slowly than the others. This became clinically apparent at the age of 5.6 years. In all five metacarpals growth ceased at the same time, indicating that the abnormally short size of the two metacarpals did not result from early epiphyseal closure.     

INTERNATIONAL COMPARISONS OF POSTNATAL GROWTH OF LOW BIRTHWEIGHT INFANTS WITH SPECIAL REFERENCE TO DIFFERENCES BETWEEN DEVELOPING AND AFFLUENT COUNTRIES

Hofvander Y. (International Child Health Unit, Department of Paediatrics, University of Uppsala, Sweden). International comparisons of postnatal growth of low birth-weight infants with special reference to differences between developing and affluent countries. Acta Paediatr Scand, Suppl. 296:14, 1982. A large majority of low birthweight infants are born in developing countries where however, only few follow-up studies have been made. However, there are clear indications that in general the AGA infants catch-up better than the SGA of the same weight. A particularly poor catch-up growth is shown by full-term SGA indicating that if a fetal growth retardations is diagnosed, delivery should be induced prematurely. Social and environmental factors are important for the optimal growth postnatally and particularly so if the environmental conditions are adverse.     

CELL POPULATIONS IN THE BONE MARROW OF GUINEA PIG FETUSES WITH INTRAUTERINE GROWTH RETARDATION

Bone marrow smears and blood samples were examined in guinea pig fetuses in which intrauterine growth retardation (IUGR) had been induced by uterine artery ligation and compared with those of control (well-grown) fetuses from uterine horns with intact circulation. Differential bone marrow cell counts were obtained from a count of 300 cells per smear and blood samples were assayed for hemoglobin concentration and 2,3-diphosphoglycerate (DPG). Results of blood assays showed no difference in hemoglobin concentration. DPG levels were reduced in the IUGR guinea pigs (.05), which could be a consequence of decreased glucose availability or represent an adaptation to reduced oxygen availability. Comparisons of bone marrow counts revealed an increase in total erythrocyte precursors (.05) and a decrease in total granulocytic precursors (.05) in IUGR fetuses. Within the erythroid lineage there was a significant increase in late (orthochromatic) erythroblasts (.005) in the IUGR animals compared with control animals. The granulocytic lineage of the IUGR fetuses showed a significant decrease in mature neutrophils (.05) and eosinophilic precursors (.05) compared with controls. These data suggest that the hypoxic stress of uterine artery ligation leads to an increase in medullary erythropoiesis. In concert with a previous study that showed a reduction in hepatic erythropoiesis, these data suggest a precocious shift of the anatomic site of erythropoiesis from the liver to the bone marrow under conditions of hypoxia.     

A FOLLOW-UP STUDY OF PHYSICAL GROWTH FOLLOWING FAILURE TO THRIVE WITH SPECIAL REFERENCE TO A CRITICAL PERIOD IN THE FIRST YEAR OF LIFE

This was a follow-up study of physical growth of children who have had failure to thrive. It comprised 77 children in whom the cause was corrected and 35 children with persistent organic cause together with 10 children in whom the patent ductus arteriosus was ligated after the first year. The treated group consisted of surgical and medical cases. Their pattern of growth was compared with that of a control group composed of 75 children from the fracture clinic and 24 siblings, all from the same age range and nearly the same mean age. Seven parameters of growth were tested. Significant retardation in six parameters was noted in both the treated group (in which the cause of failure to thrive was removed) and the untreated group (in which the treatment of the cause was impossible). In the treated group, the mean skeletal age was less retarded than the mean height, while the mean head circumference of females was significantly more retarded than that of males. There was only slight difference between early and late ligation of patent ductus arteriosus in subsequent physical growth. Neither the very early onset of failure nor its severity caused a severe retardation within the treated group. Prolonged duration of failure to thrive or failure to correct the cause in the first year led to significant subsequent growth retardation within the treated group. Parental height and birth weight played a less well defined role, while socio-economic environment played a minor role in causing growth retardation in the treated group. The first year can only be regarded as a relatively critical period concerning subsequent physical growth due to difficulty in separating the effect of illness from that of genetic endowment. Growth retardation may represent another congenital abnormality independent of the original anomaly which was corrected. The importance of reduced cell number was discussed.     

COMBINED TEST OF HYPOTHALAMIC-PITUITARY FUNCTION IN GROWTH RETARDED CHILDREN TREATED WITH GROWTH HORMONE I. Secretion of Growth Hormone and Somatomedin before and after Treatment

Abstract. Kastrup, K. W., Andersen, H., Eskildsen, P. C., Jacobsen, B. B., Krabbe, S. and Petersen, K. E. (Children's Hospital, Fuglebakken and Herlev Hospital, Copenhagen, Denmark). Combined test of hypothalamic—pituitary function in growth retarded children treated with growth hormone. Acta Paediatr Scand, Suppl 277: 9, 1979.—In 23 growth retarded children two consecutive insulin tolerance tests (ITT) were performed to establish a diagnosis of growth hormone (GH) deficiency. Nine children did not respond (GH peak value less than 8 mU/l), whereas 14 were classified as having partial GH deficiency (GH peak value less than 20 mU/l). All were treated for an average period of 40 months with human growth hormone (HGH). In a combined stimulation test at the end of the treatment period 9 children demonstrated a persistent GH deficiency, whereas a normal response was found in 14 of the previous partial GH deficient children. During treatment the monthly growth rate rose from 0.21 cm to 0.58 cm in the GH deficient children and from 0.31 cm to 0.70 cm in the partial deficient children, in most of whom spontaneous pubertal development occurred during treatment. Somatomedin (SM) values were decreased in the GH deficient children before and after treatment but increased to normal levels during treatment. Growth velocity in these children during treatment was correlated to SM values before treatment. In the partial GH deficient children SM values were subnormal before but normal after treatment. This supports the assumption that in some children with constitutional delay in puberty a reversible functional hypopituitarism exists, which is normalized after the onset of puberty, due to androgens sensitizing growth hormone releasing mechanisms. Treatment with HGH may induce increased growth velocity in some of these patients.     

GROWTH HORMONE AND SOMATOMEDIN A IN GIRLS WITH ADOLESCENT IDIOPATHIC SCOLIOSIS

Abstract. Girls with adolescent idiopathic scoliosis are taller than nonscoliotic girls of the same age. This observation may be related to factors regulating longitudinal growth. Plasma growth hormone was determined in a group of scoliotic girls by double antibody radioimmunoassay under the following conditions: 1) Insulin induced hypoglycemia, 2) glucose tolerance test, 3) exercise. Somatomedin A was determined by a method based on the ability of serum to stimulate the incorporation of radioactive sulphate in embryonic chick cartilage. The results were compared with those obtained in a control group of healthy nonscoliotic girls of comparable age. After overnight fasting and after at least one hour's rest the basal growth hormone level was 9.8 ± 11.1 (±S.D.) ng/ml in the scoliotic girls ( n =48) and 2.2 ± 1.1 ng/ml in the controls ( n =15). This difference is significant. In the hypoglycemia test the peak growth hormone level tended to be higher in the scoliotic girls but the difference is not significant. In the exercise test the maximal value was reached at different times in the two groups: at 20 min after start of the exercise in the scoliotic girls ( n =14, 17.3±11.8 ng/ml) and at 40 min in the controls (n=9, 16.0±6.6 ng/ml). In the glucose tolerance test the growth hormone level was suppressed in both groups but the mean values tended to be higher during the first 120 min in the scoliotic girls. The serum somatomedin levels were higher in the group of scoliotic girls ( n =19, 1.13±0.17 U/ml) than in the controls ( n =14, 0.88±0.16 U/ml) and the difference is significant. The results obtained are difficult to interpret but suggest that growth hormone secretion is higher in girls with adolescent idiopathic scoliosis than in healthy girls of comparable age.     

THE EFFECT ON GROWTH OF CHILDHOOD ASTHMA

ABSTRACT. Martin, A. J., Landau, L. I. and Phelan, P. D. (Department of Thoracic Medicine, Royal Children's Hospital, Melbourne, Australia). The effect on growth of childhood asthma. Acta Paediatr Scand, 70:683,.–The effect on growth of asthma has been documented in a prospective study from age 7 to 21 years in a randomly selected group of 342 subjects. These subjects covered the whole spectrum of childhood wheezing. Growth suppression was first noted at 10 years of age in the more severely affected groups and was most marked at 14 years of age. By 21 years of age, all groups had achieved a height and weight not significantly different from control subjects. Growth delay occurred in children with more persistent asthma even if they had never received oral corticosteroid therapy but growth was more delayed in those receiving oral steroids. The effect of steroids was most significant in those with frequent episodic asthma whose asthma alone was probably not sufficiently severe to retard growth.     

LINEAR GROWTH RATE, BONE MATURATION AND GROWTH HORMONE SECRETION IN PREPUBERTAL CHILDREN WITH CONGENITAL ADRENAL HYPERPLASIA

This study was designed to evaluate the effect of various oral hydrocortisone dosages on linear growth and bone maturation in a group of 21 children with congenital adrenal hyper-plasia between the age of 3 and 10 years. Treatment was monitored on urinary pregnanetriol excretion. When considering the individual annual height increment, a normal growth rate was achieved with dosages between 15 and 36 mg/per 24 hours, and a reduced growth rate with dosages between 27 and 55 mg/ per 24 hours. The same range of dosages was found when bone maturation increments were considered separately. In order to study the dose-response relationship, the slopes of individual linear growth curves (considered for minimal periods of two years) were correlated with hydrocortisone dosages. A significant negative correlation was found which assesses the growth reducing activity of hydrocortisone for dosages up to 45 mg/per 24 hours. Linear growth of children overtreated during early infancy did not show a normal catch up rate in some cases, suggesting a permanent damage of growth. In all cases growth hormone secretion was in the normal range. In late treated children, dosages between 30 and 45 mg/ per 24 hours reduced predominantly the skeletal maturation and allowed some linear growth.     

THE EFFECTS OF GROWTH HORMONE THERAPY IN CHILDREN WITH RADIATION-INDUCED GROWTH HORMONE DEFICIENCY

Abstract. Shalet, S. M., Whitehead, E., Chapman, A. J. and Beard well, C. G. (Department of Endocrinology, Christie Hospital, Manchester, England). The effects of growth hormone therapy in children with radiation-induced growth hormone deficiency. Acta Paediatr Scand, 70:81, 1981.–The effects of growth hormone (GH) therapy were studied in 6 children, previously treated for brain tumours which did not directly involve the hypo-thalamic-pituitary axis, and who had received cranial irradiation between 2.1 and 10 years earlier. All 6 were short with a standing height standard deviation score (SDS) from -1.7 to -3.3. Impaired growth hormone responses to an insulin tolerance test (ITT) were observed in all 6 and to a Bovril stimulation test in 5 children. The remainder of pituitary function was essentially normal. All 6 were prepubertal and 5 had a retarded bone age. During the pre-treatment year the 6 children's grow lb rates varied from 2.0 to 5.1 cm. Subsequently all received human GH in a dose of 5 units 3 times weekly for 1 year. The growth rate in each was at least 2 cm greater during the treatment year than the pre-treatment year. Growth during the treatment year ranged from 6.0 to 10.1 cm. In 5 of the 6 the improvement in growth rate could be totally ascribed to the GH therapy. In the sixth there was significant pubertal maturation during the treatment year and only in this subject did the bone age advance at a significantly greater rate than the chronological age.     

应用细胞生长因子提高再生障碍性贫血患者造血干细胞质量的研究

为探讨再障发病机制中各种造血生长因子（ＨＧＦｓ）对其造血干细胞的影响,了解各种ＨＧＦｓ对造血干细胞生长、增殖的具体作用及相互间的协同作用,采用甲基纤维素半固体体外短期培养及长期液体培养的方法,观察ＨＧＦｓ如粒一巨噬细胞集落刺激因子（ＧＭ—ＣＳＦ）、粒细胞集落刺激因子（Ｇ—ＣＳＦ）、白细胞介素－３（ＩＬ—３）、ＩＬ—６、干细胞因子（ＳＣＦ）、促红细胞生成素（Ｅｐｏ）以及ＨＧＦｓ不同组合方式对再障患者骨髓造血干细胞增殖、分化的调控作用。发现再障患者的克隆形成细胞（ＣＦＣ）形成巨噬细胞粒细胞集落形成单位（ＣＦＵ—ＧＭ）和红系爆发式集落形成单位（ＢＦＵ—Ｅ）的能力受限,但大部分患者（１０／１２）骨髓中长期培养起始细胞（ＬＴＣ—ＩＣ）接近正常,提示再障的造血干细胞可能在分化成熟过程中受到阻碍所致。此外,各种ＨＧＦｓ均有不同程度的提高造血干细胞形成集落的能力,且不同ＨＧＦｓ之间对再障患者ＣＦＣ形成ＣＦＵ—ＧＭ、ＢＦＵ—Ｅ的能力同样具有协同作用,其中以ＳＣＦ、ＩＬ—３和ＣＭ—ＣＳＦ的联合应用更为显著（Ｐ＜０．００１）。     

SCREENING FOR VIRAL INFECTIONS IN INFANTS WITH POOR INTRAUTERINE GROWTH

ABSTRACT. Andréasson, B., Svenningsen, N. W. and Nordenfelt, E. (Department of Paediatrics and Department of Medical Microbiology, University Hospital, Lund, Sweden). Screening for viral infections in infants with poor intrauterine growth. Acta Paediatr Scand 70:673,.–Viral excretion and immunoglobulin concentration during the first 3 days of life were studied in a consecutive study of 104 infants with poor intrauterine growth. Other possible etiologies of poor intrauterine growth were analysed retrospectively. The etiology of poor intrauterine growth could not be found in 34 % of the babies. The data obtained showed no etiological relationship between poor intrauterine growth in our population and viral infection.