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Controlled fasts can play a valuable role in the diagnosis and management of hypoglycaemia in paediatric clinical practice, but are no substitute for the collecting of appropriate critical samples at the time of hypoglycaemia for metabolic and endocrine studies. Fatty acid oxidation defects, hyperinsulinism and adrenal insufficiency should always be excluded prior to organising controlled fasts. Controlled fasts are safe if conducted in an experienced setting with strict protocols in place. Failure to adhere to protocol can defeat the purpose of the study and can potentially be dangerous. Proper planning in conjunction with the laboratory and close supervision by staff experienced in controlled fasts is crucial to ensure the best quality information is yielded from these procedures.

This two‐center retrospective study shows an unexpected high mortality rate and wide range of complications occurring in 12 patients suffering from propionic acidemia who underwent liver transplantation over the last 20 years.

Propionic acidemia (PA) is a severe metabolic disorder with cardiac and neurologic complications and a poor quality of life. Liver transplantation (LT) was thus proposed in PA to increase enzyme activity. We studied retrospectively LT in PA in two European centers. Twelve patients underwent 17 LTs between 1991 and 2013. They developed severe, unusual and unexpected complications, with high mortality (58%). When present, the cardiomyopathy resolved and no acute metabolic decompensation occurred allowing dietary relaxation. Renal failure was present in half of the patients before LT and worsened in all of them. We suggest that cardiac and renal functions should be assessed before LT and monitored closely afterward. A renal sparing immunosuppression should be used. We speculate that some complications may be related to accumulated toxicity of the disease and that earlier LT could prevent some of these consequences. As kidney transplantation has been performed successfully in methylmalonic acidemia, a metabolic disease in the same biochemical pathway, the choice of the organ to transplant could be further discussed.

The process of growth can be considered to occur in four phases, namely intrauterine, infancy, early childhood and the pubertal growth spurt. Each of these components is regulated by different factors. During the intrauterine life growth is regulated by genetic, maternal, nutritional, placental and growth promoting factors. In infancy growth is dependent upon nutrition, whereas in early childhood growth hormone and thyroid hormones become important in regulating growth. Finally, the pubertal growth spurt is controlled by a combination of growth hormone and sex steroids.

The causes and geographic distribution of 267 cases of iatrogenic Creutzfeldt–Jakob disease (CJD) are here updated at the millennium. Small numbers of still-occurring cases result from disease onsets after longer and longer incubation periods following infection by cadaveric human growth hormone or dura mater grafts manufactured and distributed before the mid-1980s. The proportion of recipients acquiring CJD from growth hormone varies from 0.3 to 4.4 in different countries, and acquisition from dura mater varies between 0.02 and 0.05 in Japan (where most cases occurred). Incubation periods can extend up to 30 years, and cerebellar onsets predominate in both hormone and graft recipients (in whom the site of graft placement had no effect on the clinical presentation). Homozygosity at codon 129 of the PRNPgene is over-represented in both forms of disease; it has no effect on the incubation period of graft recipients, but may promote shorter incubation periods in hormone cases. Knowledge about potential high-risk sources of contamination gained during the last quarter century, and the implementation of methods to circumvent them, should minimize the potential for iatrogenic contributions to the current spectrum of CJD.

OBJECTIVE: To identify predictors of postnatal catch-up growth from birth to two years and its relation to size and obesity at five years. DESIGN: Regional prospective cohort study. SETTING: Avon longitudinal study of pregnancy and childhood, United Kingdom. SUBJECTS: 848 full term singletons from a 10% random sample of the Avon longitudinal study of pregnancy and childhood. MAIN OUTCOME MEASURES: Maternal birth weight, prepregnancy weight, pregnancy weight gain, height, smoking, and parity, and paternal height. Weight and length of infants at birth, two years, and five years expressed as standard deviation (SD) scores from the UK reference scores for 1990. Percentage fat mass and total fat mass (estimated from skinfolds) and waist circumference at five years. RESULTS: Size at birth was representative of the national reference. Overall, 30. 7% (260 of 848) of infants showed a gain in SD score for weight greater than 0.67 SD scores between zero and two years, indicating clinically significant catch-up growth. These children had lower weight, length, and ponderal index at birth than other children, and were more often from primiparous pregnancies. They also had taller fathers than other children, and their mothers had lower birth weights and were more likely to smoke during pregnancy. Children who showed catch-up growth between zero and two years were heavier, taller, and fatter (body mass index, percentage body fat, and waist circumference) at five years than other children. CONCLUSIONS: In this contemporary well nourished cohort, catch-up growth was predicted by factors relating to intrauterine restraint of fetal growth. Children who showed catch-up growth between zero and two years were fatter and had more central fat distribution at five years than other children. Mechanisms that signal and regulate early catch-up growth in the postnatal period may influence associations between small size at birth and risks for disease in adulthood.

Sixty patients with the diagnosis of idiopathic growth hormone deficiency have been followed till final height was reached, after hGH treatment lasting between 2 and 15 (average 5.4) years. Twenty-six had ‘total’ and 13 ‘partial’ isolated growth hormone deficiency (IGHD); 10 had GHD plus gonadotrophin deficiency (GnD); six had multiple pituitary hormone deficiency (MPHD) and five, labelled ‘transient prepubertal GHD’, had normal responses in the insulin tolerance test when retested after the end of treatment.

The biochemical and endocrine responses of 13 patients with hepatic glycogen storage disease (HGSD) (type I-six patients, type Ib-two, type III-three, type IX-two patients) to an oral glucose load have been investigated. Longitudinal growth data was available in all patients. The height velocity standard deviation score (HVSDS) was positively correlated with the plasma somatomedin and inversely correlated with the glucose-insulin ratio, plasma cortisol and plasma growth hormone concentrations. There was no correlation between plasma glucagon and HVSDS. Free fatty acid and lactate concentrations were highest in the older untreated patients who were growing slowly.

We have examined the growth and skeletal maturation of 19 children (6 male, 13 female) with central precocious puberty. The aetiology in nine patients (5 male, 4 female) was secondary to a hypothalamic hamartoma. Six children (2 male, 4 female) received no treatment whereas 13 children (4 male, 9 female) were treated with cyproterone acetate in a mean dose of 68 mg/m2 per day (range, 34–260) for a mean duration of 4.5 years (range, 0.8–7.9). There was no significant difference between height SDS for bone age at the beginning and end of observation in either treated or untreated groups. No significant relationship between the mean dose of cyproterone acetate used and change in height SDS for bone age could be determined. We conclude that cyproterone acetate has no beneficial effect on the growth prognosis of children with central precocious puberty.

The secular trends in height, sitting height and leg length in Japanese children have been studied by fitting Preece-Baines Model I curves to the annual mean values from ages five to 17 of school data collected in 1957, 1967 and 1977. The method provides estimates of final adult value, and of age of maximum annual increment.Between 1957 and 1977 the maximal increments in height, sitting height and leg length all became earlier, by about a year in boys and a little less in girls. Japanese now mature about a year earlier than North Europeans. Adult height increased by 4·3 cm in boys and 2·7 cm in girls between 1957 and 1977, the increment being less in the second decade than in the first. Sitting height showed practically no increase whatever; almost the whole secular trend was due to change in leg length. Japanese now have trunk/leg proportions much more similar to those of North Europeans than was the case 20 years ago, but their adult height remains about one standard deviation lower.

Élite adult athletes are known to have physical and physiological characteristics specifically suited to their sport. However, it is not clear whether the observed adult differences arise because of training or whether the sport selects the individual with the appropriate characteristics. The purpose of this prospective study was to compare and contrast the physical development of young athletes (8–19 years), and in so doing provide a possible response to this question. Development of anthropometric characteristics and sexual maturation were assessed in a group of 232 male athletes for three consecutive years. Parental heights were used to predict target heights. The subjects were a randomly selected group of young British athletes, from four sports: soccer, gymnastics, swimming and tennis. Using a linked longitudinal cohort study design (age cohorts 8, 10, 12, 14 and 16 years) it was possible to estimate a consecutive 11-year development pattern, over the 3-year testing period. The adjusted mean (ANCOVA) height, accounting for age and pubertal status, of male swimmers (161·6 ± 0·6 cm) was found to be significantly greater (p < 0·01) than gymnasts (150·7 ± 0·8 cm) and soccer players (158·7 ± 0·6 cm), and their adjusted mean body mass (51·3 ± 0·6 kg) significantly greater (p < 0·01) than the other groups. When testicular volumes were compared, it was found that swimmers had significantly larger volumes than gymnasts and tennis players from 14 to 16 years of age (p < 0·05). Gymnasts' growth curve of testis size was characteristic of late maturers, the swimmers' curve was characteristic of early maturers. As all the young athletes started training prior to puberty the observed late sexual maturation of gymnasts and early maturation of swimmers suggests some form of sports-specific selection. Training did not appear to have affected these young athletes's growth and development; rather their continued success in sport appeared to be related to inherited traits.

It has been hypothesized that young athletes, undertaking intensive training, have delayed menarche due to the effects of training at an early age, although it is known that other genetic and environmental factors contribute to this observed later menarche. As part of a longitudinal study of the effects of intensive training during puberty and adolescence we investigated age of menarche in 222 athletes and their mothers. All the sports studied (gymnastics, swimming and tennis) had later mean ages of menarche (14·3, 13·3 and 13·2 years respectively) than the previously reported UK reference value of 13·00 years. A positive correlation was found between menarcheal age in mothers and daughters (r=0·27, p<0·01). Analysis of covariance, using maternal menarcheal age, socioeconomic group, duration of training and type of sport, confirmed that maternal menarcheal age and type of sport were having a significant influence on subject's age of menarche. As maternal menarcheal age and sport were the best predictors of menarcheal age in the athletes we studied, it would appear that menarche was intrinsically late rather than delayed. This suggests that some form of sport-specific selection may have occurred. It therefore seems likely that late maturation of gymnasts contributes to a girl's decision to continue participating in the sport rather than intensive training delaying menarche.

Co-trimoxazole is an effective antibacterial agent for the prophylaxis of urinary tract infection. Because experimental evidence raises the possibility that high-dose cotrimoxazole might interfere with normal somatic growth, the longitudinal growth and growth velocities were analysed in 114 girls receiving long-term, low-dose prophylactic cotrimoxazole. They were aged 2–12 years at the start of prophylaxis which was given in a daily dose of approximately 10 mg sulphamethoxazole (SMX) and 2 mg trimethoprim (TMP)/kg body weight for at least 6 months and for up to 6 years.

The Preece-Baines Model 1 curve has been fitted to longitudinal data on growth in height of 105 boys and girls in 70 Bengal families: 60 of these were sibs distributed in 25 families. For a number of growth characteristics, such as age at peak height velocity, the proportion of the total population variance that was due to variation between, as opposed to within, families was estimated by Smith's (1980) method. The proportions for age at take-off of the adolescent spurt, of age at PHV, and of PHV itself were 22%, 26% and 33% (where adult height gives a value of about 40%). The sample is small and these estimates have high standard errors and need confirmation.

This study is the first Indian longitudinal growth survey from early childhood to maturity. The heights of 303 boys and 260 girls, from middle-class families in a semi-urban area south of Calcutta, were measured at regular intervals over periods of up to 14 years (between 1952 and 1966). The data were analysed using appropriate mixed longitudinal and curve-fitting techniques.Growth in height of these middle-class Bengali children, who are not a representative sample of the Indian population, is slightly above the national Indian Council of Medical Research Standards. In both sexes, mean heights are below the 10th centile line of the British standards from an early age onwards, mainly due to a smaller prepubertal growth.The adolescent growth spurt in the Indians is similar to that seen in British children, as is the age at which it occurs (peak height velocity at 14·0 years in boys, 12·5 years in girls). The sex difference of 14·0 cm in adult stature is attributable to a greater adolescent gain in the boys of 6·0 cm, a greater height in boys at the girls' age at take-off of 3·3 cm and a gain in height by the boys of 4·7 cm between the girls' and boys' ages at take-off.

A new family of mathematical functions to fit longitudinal growth data is described. All members derive from the differential equation dh/dt=s(t). (h1-h) where h1 is adult size and s(t) is a function of time. The form of s(t) is given by one of many functions, all solutions of differential equations, thus generating a family of different models.Three versions were compared. All were superior to previously described models. Model 1, in which s(t) was defined by ds/dt=(s1-s)(s-s0) was especially accurate and robust, containing only five parameters to describe growth in stature from age two to maturity.Derived “biological” parameters such as Peak Height Velocity were very consistent between these three members of the family but, in some cases, differed significantly from previous estimates.

Total body water was measured in 26 children and adolescents using the stable isotope H 2 O 18 . Body resistance was measured using a tetrapolar technique with a constant 50Khz, 800 µ A alternating current. Total body water was highly correlated ( r =0·97; P

We report the treatment of 44 boys with constitutional delay of growth and puberty (CDGP) at a mean chronological age of 14.3 years (range, 12.4–17.1) and bone age of 12.1 years (range, 9.1–15.0). All were below the 3rd height percentile for chronological age. They reccived monthly intramuscular injections of depot testosterone esters (50 mg) for a mean period of 0.35 years (range, 0.25–0.5). Means (SD) height velocity was 4.5 (1.5) cm/year during a pretreatment period of 0.5 years. During a period of 0.9 years which included the period of treatment with depot testosterone, mean growth velocity increased to 8.8 (1.9) cm/year (P<0.001). In the initial 1.8 years following the cessation of treatment growth velocity was sustained at 7.0 (1.7) cm/year. Pretreatment height standard deviation score (SDS) for bone age was −0.89 and this gradually reduced over the next 1.5 years to a minimum of −1.48. Thereafter, height SDS for bone age gradually increased to attain a value of −1.2, 3 years after the commencement of therapy (P<0.02). The same pattern of an initial decrease, followed by an increase, in height prediction was also observed when TW2 height prediction was analysed. Sexual maturation progressed during treatment, with mean testicular volume increasing both during and after treatment, confirming the diagnosis of CDGP. The time interval for progress through puberty was shorter in boys with testosterone therapy than in the normal population. The mean duration of puberty was 2.2 years compared to 3.3 years in normal boys. We conclude that low-dose depot testosterone treatment is safe and effective for boys with CDGP. At the dose regimen used there was no suppression of testicular enlargement. Initial decrease in height prediction concomitant with depot testosterone therapy may be misleading.

The spontaneous growth of 386 patients (163 girls and 223 boys) with Silver-Russell syndrome (SRS) was analysed in a mixed longitudinal and cross-sectional manner. One hundred and twenty patients were seen in the two centres between 1970 and 1993, additional definite cases were added from the literature. Mean (± SD) length of full-term babies with SRS at birth was 43.1±3.7 cm (n=102) in both sexes. Mean weight at birth was 1940±353 g in boys and 1897±325 g in girls. During the first 3 years of life there was poor growth with a further loss in height. Between ages 4 and 10 years there was constant growth in parallel to the 3rd percentile with a mean height SDS of −4.3. The pubertal growth spurt was reduced in the whole group. Bone age development paralleled growth, retardation increased during the first years, remained constant during prepubertal time and caught up in early puberty. Mean adult height was 151.2±7.8 cm in males and 139.9±9.0 cm in females. Head circumference for age was in the lower normal range (mean SDS for 156 prepubertal boys −1.8; mean SDS for 97 prepubertal girls ≈2.2).

Hypopituitary dwarf mice were found to have reduced levels of serum somatomedin-like activity compared with normal mice of the Snell strain. Treatment with bovine growth hormone for 3 and 7 days resulted in growth without significantly increased levels of serum somatomedin-like activity, as detected by in-vitro uptake of 35SO42−into normal rat cartilage; only after treatment for 14 days was somatomedin activity significantly raised. However, treatment for 2 days with bovine growth hormone, bovine prolactin or thyroxine resulted in a dose-dependent increase in in-vivo uptake of 35SO42−into dwarf mouse costal cartilage; growth hormone and thyroxine did not act synergistically. Ten days of treatment with growth hormone promoted a dose-dependent increase in both growth (increased weight gain and tail length) and in-vivo uptake of 35SO42−. Increase in tail length was correlated with uptake of 35SO42−. Thus, in-vivo uptake of 35SO42−into dwarf mouse costal cartilage provides a sensitive method for detecting a dose-related effect of growth hormone.

Monoclonal antibodies of certain epitope specificity have been shown to produce a marked dose-dependent enhancement of the somatogenic and lactogenic activity of human GH (hGH). Two antibodies (EB1 and EB2), binding to distinct antigenic determinants and expressed on both hGH and human chorionic somato-mammotrophin (hCS), significantly enhanced the hGH-stimulated uptake of 35S-labelled sulphate into cartilage. Similarly, these antibodies enhanced the lactogenic activity of both hGH and hCS in the pigeon crop sac test. Two hGH specific monoclonal antibodies (QA68 and NA71), defining a further two epitopes, exhibited only modest enhancing or inhibitory activity in these assays, whereas the binding of certain combinations of monoclonal antibodies resulted in either reversal of enhancement or inhibition of hormone activity. Univalent antibody fragments derived from EB1 were as enhancing as the intact antibody indicating that bivalency dependent mechanisms were not involved in the phenomenon. Enhancing monoclonal antibodies were relatively poor inhibitors of 125I-labelled hGH binding to liver microsomal receptors, which is in contrast with their previously described property of potent suppression of hGH interaction with lymphoid cell receptors. It is tentatively concluded that 'restriction' of hormone binding to particular hGH receptors, relevant to somatic growth or lactogenic activity, may play a role in the enhancement phenomenon of hGH in vivo.J. Endocr.(1986) 110,381–388

Summary: A patient with riboflavin-responsive mild multiple acyl-CoA dehydrogenation deficiency of the ethylmalonic-adipic aciduria type experienced a recurrence of spontaneous hypoglycaemic episodes whilst being given supplementaryL-cartinine. This phenomenon is explicable in terms of the known biochemical features of this condition and suggests caution in the carnitine supplementation of patients with defective oxidation of medium- or short-chain fatty acyl-CoA esters. This patient excreted excessive phenylpropionylglycine after an oral phenylpropionic acid load. Thus the phenylpropionic acid loading test is not completely specific for primary medium-chain acyl-CoA dehydrogenase deficiency as has been supposed.

The effect of pressure, warmth, and control stimuli applied to the axilla and lateral chest wall on unilateral nasal airway resistance and facial skin temperature was investigated in 60 healthy adults. Nasal resistance was measured by posterior rhinomanometry and skin temperature with an infrared thermometer. A significant increase in unilateral nasal resistance ipsilateral to the applied stimulus was seen with both pressure and warmth (p 0.006, p 0.02). A decrease in unilateral nasal resistance contralateral to the stimulus was seen in both these groups, but this was not significant (p 0.45, p0.81). The control stimulus group showed a non-significant increase in unilateral nasal resistance ipsilateral to the applied stimulus (p 0.55), and a significant rise in unilateral nasal resistance on the contralateral side (p 0.008). There were no significant differences between the ipsilateral and contralateral facial skin temperatures before or after the application of a unilateral pressure, warm or control stimulus. A significant bilateral increase in facial temperature was observed during the course of the experiment in all three groups. The mechanisms of induced changes in unilateral nasal resistance are discussed. The results increase our knowledge of the corporo-nasal reflex and demonstrate that the reciprocal changes in sympathetic tone to the nasal capacitance blood vessels are independent from any parallel reflex changes in sympathetic tone to cutaneous blood vessels.

A patient with riboflavin-responsive mild multiple acyl-CoA dehydrogenation deficiency of the ethylmalonic-adipic aciduria type experienced a recurrence of spontaneous hypoglycaemic episodes whilst being given supplementaryL-cartinine. This phenomenon is explicable in terms of the known biochemical features of this condition and suggests caution in the carnitine supplementation of patients with defective oxidation of medium- or short-chain fatty acyl-CoA esters. This patient excreted excessive phenylpropionylglycine after an oral phenylpropionic acid load. Thus the phenylpropionic acid loading test is not completely specific for primary medium-chain acyl-CoA dehydrogenase deficiency as has been supposed.

Abstract. We have examined physiological nocturnal secretion of gonadotropins in 6 boys and 2 girls with end-stage renal disease, who had either delayed or disturbed puberty. The 5 patients treated by dialysis had reduced gonadotropin pulsatility for their stage of pubertal maturation, whereas the 3 patients with successful kidney grafts demonstrated a higher nocturnal rise and increased amplitude of gonadotropin pulsatility. It is suggested that the improved gonadotropin pulsatility of transplanted patients is due to their restored renal function.

Serum from adrenalectomized rats was equipotent with serum from non-adrenalectomized animals when measured in a rat cartilage somatomedin bioassay. Extraction with butanol of sera from normal or adrenalectomized rats reduced their potency in the somatomedin bioassay rather than increasing it as has been previously reported. Butanol-soluble inhibitors of cartilage metabolism were found in sera from both normal and adrenalectomized rats. Cortisol and corticosterone, up to mildly supraphysiological levels, were found to have no effect on basal cartilage metabolism. These results suggest that physiological levels of glucocorticoids do not exert an inhibitory effect on the uptake of 35SO42−into immature rat cartilage. Since butanol-soluble inhibitors of cartilage metabolism were found in adrenalectomized rat serum it is unlikely that these substances are glucocorticoids.

Human somatomedin C has been purified from Cohn fraction IV paste by a simplified procedure using chromatofocusing, hydroxylapatite chromatography and reverse-phase high performance chromatography. The purified material has a specific activity by somatomedin C radioimmunoassay of 9160 units/mg (1 unit is defined as the amount of somatomedin present in 1 ml normal adult male human serum), representing a 650 000-fold purification, and possesses sulphation, mitogenic and insulin-like activities (specific activities of 3388 units/mg, 832 units insulin equivalents/mg and 1122 units/mg respectively). Somatomedin C is shown to be a potent stimulator of DNA synthesis (50% maximum stimulation at 150 fmol/ml) in isolated chondrocytes derived from costal cartilage, a major physiological target tissue.J. Endocr.(1986) 110,151–158

To update the British growth reference, anthropometric data for weight, height, body mass index (weight/height) and head circumference from 17 distinct surveys representative of England, Scotland and Wales (37,700 children, age range 23 weeks gestation to 23 years) were analysed by maximum penalized likelihood using the LMS method. This estimates the measurement centiles in terms of three age-sex-specific cubic spline curves: the L curve (Box–Cox power to remove skewness), M curve (median) and S curve (coefficient of variation). A two-stage fitting procedure was developed to model the age trends in median weight and height, and simulation was used to estimate confidence intervals for the fitted centiles. The reference converts measurements to standard deviation scores (SDS) that are very close to Normally distributed – the means, medians and skewness for the four measurements are effectively zero overall, with standard deviations very close to one and only slight evidence of positive kurtosis beyond ±2 SDS. The ability to express anthropometry as SDS greatly simplifies growth assessment. © 1998 John Wiley & Sons, Ltd.

The growth-promoting effects of a partially purified preparation of somatomedin (12·7 units/mg) were compared with those of various doses of bovine GH (5, 20 and 80 μg/day) when injected into hypopituitary dwarf mice. Growth parameters studied were body-weight and tail-length velocities (calculated as the slope of a regression line fitted to daily measurements against time), uptake of 35SO2−4into costal cartilage in vivoand organ weights (heart, liver and kidney). In the first experiment somatomedin (6·4 units/day), bovine GH and 0·9% NaCl were injected once daily in a volume of 0·1 ml for 10 days. Treatment with bovine GH promoted a significant dose-dependent increase in body-weight and tail-length velocities and 35SO2−4uptake into costal cartilage in vivo. Somatomedin also promoted a significant increase in body-weight velocity and 35SO2−4uptake, both responses were between that observed with the lowest dose of bovine GH and control values. Somatomedin did not promote increase in tail-length velocity. Organ weights did not differ significantly between any of the treatment groups when expressed as mg/g body weight. In the second experiment somatomedin (a daily total of 21·6 units/day) and 0·9% NaCl were injected three times per day in a volume of 0·033 ml, bovine GH was again injected once daily in a volume of 0·1 ml, and the treatment period was 12 days. As in the first experiment all doses of bovine GH and somatomedin promoted a significant increase in body-weight velocity. These results are consistent with the somatomedin hypothesis.

The incorporation of [3H]thymidine by rat costal cartilage in vitrowas studied at different fetal and postnatal ages and the effect of partially purified human somatomedin, mouse epidermal growth factor, platelet secretion products, insulin and growth hormone on thymidine uptake by fetal cartilage was examined. Thymidine uptake in plasma-free medium was many times greater in late fetal life than after birth. The incorporation of [3H]thymidine into costal cartilage from 21-day fetuses was significantly (P<0·05) increased above control values in the presence of 10 μg somatomedin/l, and when cartilage was incubated in medium containing somatomedin and diluted human plasma there was a synergistic action. Epidermal growth factor at a concentration of 1 ng/l was a potent stimulator of thymidine uptake. Secretion products from human platelets after their aggregation by thrombin stimulated [3H]thymidine uptake at a concentration of 2% (v/v), but were inhibitory at high concentrations. High concentrations of platelet secretion products stimulated the incorporation of [35S]sulphate by cartilage. A pharmacological concentration of 10 mu. insulin/ml stimulated [3H]thymidine uptake, but not concentrations of 1 or 100 mu./ml. Growth hormone had no effect. The results showed that fetal cartilage had a greater endogenous mitogenic activity than postnatal cartilage. While somatomedins may be important in the regulation of fetal body growth, other protein growth factors also stimulate fetal skeletal tissues.

Changes in the rate of in-vitro degradation of thyrotrophin releasing hormone (TRH) in serum as related to age have been investigated in the rat and man. In rats, no inactivation was found up to the age of 15 days but thereafter an age-related increase in inactivation was detected with approximately 75% inactivation in 60 min at 40 days and reaching a maximum of 88–93% inactivation in adult male and female animals. The human serum samples studied (both male and female) showed a similar but less clear-cut pattern of inactivation of TRH compared with that found in the rat. A physiological role for these age-related changes in the degradation of TRH remains to be established but it has been concluded that the changes observed in both rat and man may be associated with growth and development, possibly by facilitating feedback control of thyrotrophin secretion through the degradation of TRH.

This paper presents an investigation into the effects of prolonged oestrogen treatment (20 days) on basal growth and on growth stimulated by GH in hypopituitary dwarf mice. Body 35SO42−weight and tail length were measured during the treatment period and uptake of S04 into costal cartilage in vivoat the end of the treatment period. This study confirmed that treatment with human GH promotes a dose-dependent increase in body weight, tail length and uptake of 35SO42−in vivo; there was a highly significant correlation between these responses. Treatment with oestrogen alone had no significant effect on any of the parameters measured. All groups receiving combined oestrogen and human GH treatment showed a significant increase in body weight and tail length compared with animals receiving the same dose of oestrogen alone. However, the increase in body weight and tail length was significantly less in animals given the highest dose of oestrogen plus human GH than that observed in animals treated with the same dose of human GH alone. Treatment with oestrogen had no significant effect on the uptake of 35SO42−stimulated by human GH. Possible mechanisms for the growth-inhibiting effects of oestrogens are discussed.

The patterns of secretion of GH, LH, FSH and prolactin were determined over a single night (20.00–08.00 h; 15-min sampling) in 34 normal subjects (17 male, 17 female, aged 9·1–20·9 years). Plasma GH was measured by an immunoradiometric assay and LH, FSH and prolactin by radioimmunoassay in all samples. Data were analysed by Fourier transformation and cross-correlation after stationarization.The highest mean GH levels were noted in girls at Tanner stage 2/3 and in boys at stages 4/5. Prolactin levels were highest in girls at stage 4/5 and in boys at stage 2/3. LH and FSH showed a progressive rise by puberty stage in both sexes. The dominant pulse periodicities of GH and prolactin were 150–180 min in girls and 180 min in boys. LH and FSH pulse periodicity was around 90 min in early puberty and 180 min in later puberty in both sexes. LH and prolactin pulses showed a phase relationship with GH with a lag of 30–75 min (r= 0·32; P< 0·001) and 30 min (r= 0·47; P< 0·0001) respectively. Generally, LH and prolactin pulses were in phase (r= 0·42; P< 0·0001) and there was a highly significant correlation (r= 0·64; P< 0·0001) between FSH and LH pulsatility.Whereas mean overnight concentrations and pulse periodicity of the principal pituitary hormones varied between the sexes during early puberty, by the end of puberty a dominant pulse periodicity of around 150–180 min was established and there was remarkable temporal coupling of pulsatility.Journal of Endocrinology(1991) 130,141–149

A monoclonal antibody (BPL-M23) to insulin-like growth factor-I (IGF-I) was obtained following immunization of BALB/c mice with human IGF-I conjugated to ovalbumin. The affinity constant of BPL-M23 for IGF-I was 10·5 litres/nmol and the cross-reactivities of IGF-II, multiplication-stimulating activity III-2 and insulin were 08, 003 and less than 0·0001 % respectively. Porcine, bovine, ovine and rabbit sera, but not rat or mouse sera, showed substantial reactivity with the antibody.Comparison of radioimmunoassay analyses of 54 human serum samples from normal subjects and acromegalic and GH-deficient patients using BPL-M23 and a polyclonal rabbit antiserum (R557A) to human IGF-I showed a high correlation, indicating the usefulness of the monoclonal antibody in radioimmunoassay.Monoclonal antibody BPL-M23 was capable of abolishing the sulphation, mitogenic and insulin-like activities of IGF-I in in-vitro bioassays, suggesting that these activities may rely upon the same receptor-binding site which is near to the antibody-binding site.

Pineal indoles have been shown to affect the release of anterior pituitary hormones but details of the interrelationships are lacking. Using a new gas chromatography–mass spectrometry (g.c.–m.s.) assay the concentration of 5-methoxytryptophol (ML) was measured in plasma samples obtained from 16 children undergoing investigation of pituitary function for delayed growth. All the children received an insulin tolerance test (ITT) to study their endocrine response to stress. Some children received luteinizing hormone releasing hormone (LH-RH) and/or thyrotrophin releasing hormone (TRH). The change in concentration of ML during an ITT was similar to the change in concentration of blood sugar; a drop at 20 min followed by a rise at 30 min. This was not significantly altered by the administration of LH-RH or TRH, nor was there a different pattern of response in children who were deficient in growth hormone as opposed to those with idiopathic delayed growth. The fall in concentration of ML with stress may mediate the increased secretion of pituitary hormones. Alternatively, the pineal gland may respond directly to insulin.

To update the British growth reference, anthropometric data for weight, height, body mass index (weight/height) and head circumference from 17 distinct surveys representative of England, Scotland and Wales (37,700 children, age range 23 weeks gestation to 23 years) were analysed by maximum penalized likelihood using the LMS method. This estimates the measurement centiles in terms of three age‐sex‐specific cubic spline curves: the Lcurve (Box–Cox power to remove skewness), Mcurve (median) and Scurve (coefficient of variation). A two‐stage fitting procedure was developed to model the age trends in median weight and height, and simulation was used to estimate confidence intervals for the fitted centiles. The reference converts measurements to standard deviation scores (SDS) that are very close to Normally distributed – the means, medians and skewness for the four measurements are effectively zero overall, with standard deviations very close to one and only slight evidence of positive kurtosis beyond ±2 SDS. The ability to express anthropometry as SDS greatly simplifies growth assessment. © 1998 John Wiley & Sons, Ltd.

Animal experiments have suggested that the pineal gland produces an anti-gonadotropic hormone. The hamster, for example, undergoes reproductive collapse when kept in short-day periods, an effect which is abolished by pinealectomy1. Although there is little direct evidence about the endocrine role of the pineal gland in man, it has been noted that tumours of the pineal gland in young boys are associated with precocious puberty and the human pineal gland has been suggested to produce a substance that holds sexual maturation in check2. This observation has been extended by Kitay3, who has shown that destructive tumours are associated with precocious puberty whereas hyperactive tumours are associated with delayed puberty. However, no studies have described any change of pineal function with normal puberty. Because two pineal indoles, melatonin4and methoxytryptophol5, have been shown to be antigonadotropic when administered to animals6–10, we have now measured them in schoolchildren. Our findings show that in young boys there is an abrupt fall in the concentration of melatonin with advancing development suggesting that it may play an important physiological role in the control of human puberty.

We have performed a retrospective analysis of the pubertal parameters of 134 children with isolated GH insufficiency on GH treatment and compared them to the standards of Tanner and to a recent longitudinal study of growth and development in the United Kingdom. The age at onset of puberty (13.0 years in boys, 12.1 years in girls) was found to be significantly delayed (Mann-Whitney p<0.001), but duration of puberty (1.5 years in both sexes) was shortened (Kolgomarov-Smirnov p<0.01). Skeletal maturity at the onset of puberty was not advanced excluding this as a contributory factor. There was no association between dose of GH administered and the pubertal parameters. The results suggest that GH accelerates the pubertal process.