Increase In Growth Velocity Research Articles

Plasma erythropoietin levels in mice during the growth period.

Plasma erythropoietin (erythropoiesis stimulating factor(s), ESF), PCV and body weight were measured in normal mice from birth until the age of 70 d. Low but detectable ESF activity was present at birth, following by undetectable levels 12-48 h after birth. Thereafter the ESF level rapidly increased. Peak levels were obtained 15-20 d after birth. During the same phase an increased growth velocity occurred, coincident with decreased PCV levels. A fall to undetectable levels in plasma ESF activity coincided with decelleration of growth 40-50 d after birth. In small litters (four pups per litter) growth velocity and PCV levels were significantly higher than in large litters (16 pups per litter) 8 and 15 d after birth. The plasma ESF activity, however, did not differ between the two groups. Prohibiting suckling for a period of 16 h did not change the plasma ESF level. The hypothesis is put forward that growth directly or indirectly stimulates ESF production.

The combined effect of growth hormone and oxandrolone in patients with growth hormone deficiency

Twenty patients with growth hormone deficiency ranging in age from 5 5/12 to 15 8/12 years were treated for 12 months with a combination of human growth hormone and oxandrolone, followed by a period of six months off both medications. Eight of the patients received the combined therapy during the first year of hGH treatment, and 12 during either the second or fourth years of hGH administration. In considering growth velocity alone, the addition of anabolic steroid was beneficial. The bone age advanced rapidly when oxandrolone was added during the first year of hGH treatment, and less rapidly in subsequent years. The increased growth velocity, however, compensated for the acceleration of bone maturation and the overall effect of the combined treatment was beneficial, particularly when used after the first year of hGH treatment. We conclude that there is no advantage to using oxandrolone during the first year of hGH therapy, that oxandrolone in the appropriate dose is of benefit in subsequent years of hGH treatment, and that because of the individual variation in bone maturation, bone age should be frequently assessed.

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

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/1), whereas 14 were classified as having partial GH deficiency (GH peak value less than 20 mU/1). 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 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.

The effect of synthetic androgens on the hypothalamic-pituitary-gonadal axis in boys with constitutionally delayed growth

Serial concentrations of basal serum LH, FSH, testosterone, and LH and FSH responses to intravenous gonadotropin-releasing hormone were measured before and during six months of administration of fluoxymesterone or oxandrolone in 14 boys with constitutionally delayed growth and adolescence, in order to assess the effects of these androgens on maturation of the hypothalamic-pituitary-gonadal axis. Before therapy all boys had normal hormonal responses based on bone age. At the end of six months therapy 10 of the 14 boys had lower LH responses (34 to 89% reduction) to GnRH without consistent changes in FSH responses. With both androgens, there there was significant suppression of both basal serum FSH and testosterone. Eleven boys were restudied six months after completion of therapy; basal serum LH, FSH, and testosterone and responses to GnRH were equal to or greater than pretreatment levels, indicating recovery or progressive maturation of the HPGA. All boys had increased growth velocity and imporved weight gain without excessive bone age advancement; all had improved psychosocial adjustment.

Transient partial hGH deficiency in prepubertal children with delay of growth.

The hGH response to an ornithin or an insulin test was measured in 105 children from 11-18 yr old with delay of growth more than 2 SD. Besides 74 subjects with normal values and 7 with complete lack of response, 24 subjects exhibited a partial rise of GH. Most of the latter had decreasing growth rate and no sign of puberty. Out of 15 assessed for GH function after onset of puberty, 14 showed a normal response accompanying a markedly increased growth velocity. Four other subjects with partial response who were receiving sexual hormones for 48 hr before the second test showed a normal response also. An exogenous hGH treatment administered in two of these patients resulted in a marked and sustained growth increase far before entering puberty. The findings that plasma GH responses to stimulation tests is reduced in some children with decreasing growth rate before puberty and return to normal after onset of sexual development, would suggest a transient and functional defect in growth hormone secretion and the physiologic role of sexual hormones on GH release mechanism at that period of life.

Hypothyroidism in children with cystinosis.

Eight children with cystinosis (3 with renal transplants, 2 on maintenance haemodialysis, 2 with chronic renal failure, and one with normal renal function) were studied for evidence of hypothyroidism, and compared with a control group of children with chronic renal failure due to other causes. Abnormal thyroid function was present in all the cystinotic patients: thyroxine (T4) low in 1, free thyroxine index (FTI) low in 2, thyroid-stimulating hormone (TSH) raised in 6; all had a supranormal TSH response to thyrotrophin-releasing hormone (TRH) stimulation, indicating impaired thyroid reserve compared with patients in the control group who had a depressed or normal TSH response. Increased growth velocity with thyroid supplementation occurred in only 2 patients, and the onset of puberty may have contributed to this improvement. Hypothyroidism is a common finding in cystinosis, and it is suggested that thyroxine treatment be started when the TSH concentration becomes raised.

The growth and morphology of directionally solidified nickel base γ/γ′- σ superalloys

A series of Ni-Nb-Al-Cr(γ/γ′- σ) alloys in the composition ranges Nb 19.3 to 23.2 wt pct, Al 2.5 to 5.2 wt pct and Cr 0 to 7.05 wt pct have been directionally solidified under high thermal gradient (G) at both steady state and under conditions of abruptly or gradually changing growth rate(ft). The critical ratio of G andR, (g/r)*, to achieve two-phase plane frontin- situ composite growth increases as chromium and niobium (Cb) concentration deviates from the trough or surface of two-fold saturation. Interlamellar spacing of composites tend to decrease with increasing chromium content. Structures produced at steady state growth in whichG/R (G/R)*) precipitated a single phase σ (Ni3Nb) band. For alloys which at lowG/R exhibited γ dendrites a similar effect was achieved only when growth rate was reduced abruptly by more than an order of magnitude. Interlamellar spacing of two alloys (approximately Ni-20 wt pct Nb-2.5 wt pct Al-6 wt pct Cr) was studied and for abrupt reductions in growth rate in which bands were not produced, it was observed to decay slowly to the new steady state value over distances which are inconsistent with the assumption of simple niobium diffusion control. A gradual increase in growth velocity for one of these alloys resulted in extremely slow adjustment of interlamellar spacing occurring over a period greater than one hour. An abrupt increase in growth velocity for all alloys caused immediate adjustment of interlamellar spacing to the new steady state value.

LONG‐TERM THERAPY WITH 1 α‐HYDROXYVITAMIN D3 IN CHILDREN WITH‘PSEUDO‐DEFICIENCY’RICKETS

This investigation confirms that 1alpha-hydroxyvitamin D3 (1alpha-OHD3) is a potent drug for the treatment of patients with pseudo-deficiency rickets (Balsan et al., 1975a; Reade et al., 1975; Prader et al., 1976). 1alpha-OHD3 corrects their intestinal malabsorption of calcium and phosphorus, normalizes their serum calcium and phosphate concentrations and promotes healing of skeletal lesions. This study also shows differences in the needs for 1alpha-OHD3 of children with PDR. Three factors appear to be of importance: familial sensitivity, severity of chronic secondary hyperparathyroidism, and periods of increased growth velocity. Tolerance to long-term 1alpha-OHD3 therapy, at doses varying from 0.5 to 2 microgram/d is excellent. Surveillance of patients should include regular measurements of 24 h urinary excretion of calcium, since hypercalciuria is the first signal of overdosage.

Long‐term results with beclomethasone dipropionate aerosol in children with bronchial asthma: why does it sometimes fail?

1. Beclomethasone dipropionate aerosol has been shown to be a highly effective treatment for asthma in childhood, with virtual absence of side effects at this age. 2. When treatment is unsuccessful, this is usually due to failure to take it correctly and regularly. 3. A good response is usually associated with an improvement in ventilatory function and a marked increase in growth velocity.

REVERSAL OF GROWTH ARREST IN CROHN'S DISEASE(CD): A NEW APPROACH

Severe impairment of linear growth without evidence of endocrine dysfunction frequently complicates CD in childhood. The impact of nutritional intervention was studied in 7 patients(pts) (5 boys, 2 girls, ages 9-17 yrs)with CD and linear growth arrest for at least 1 yr prior to study. 6/7 were less than 3rd%; height and bone ages ranged 5-11 and 6-13 yrs respectively. All were in clinical remission; 3 were maintained on a constant dose of steroid. Fasting somatomedin (3/3) and stimulated growth hormone levels (5/5) were normal. On metabolic balances prior to therapy, 5 pts demonstrated inadequate caloric intake (50±20 kcal/kg;normal for height 75-85 kcal/kg); none had positive nitrogen balance; 1 had steatorrhea. Oral feeding was supplemented with intravenous hyperalimentation to total daily intake of 77±8 kcalAg for 6-8 wks. During treatment, lean body mass(40K) increased 2.2-7.3 kg in 5 pts studied. All pts exhibited weight gain (range 2.4-7.4 kg), linear growth (range 1.0-2.3cm), and a significant increase in growth velocity (0.7±0.2cm/month, p<.001). Linear growth persisted following therapy and averaged 0.4±.3cm/month(p<.02) for 3-6 months. Subsequent growth in the 4 pts with long-term followup has totalled 2.5, 9, 10 and 20 cm respectively at 1.5-2.5 yr. The lowest growth increment occurred in the only pubertal pt. Conclusions: 1. Inadequate caloric intake explains the growth arrest in these children with CD; 2. caloric supplementation via intravenous hyperalimentation produces improvement in anthropometric values and a dramatic linear growth spurt that continues after therapy is terminated.

Role of dietary energy supplementation in growth of children with chronic renal insufficiency.

The effect of dietary energy supplements in children with varying degrees of chronic renal insufficiency was investigated. Despite an increased energy intake of 8-4% there was no increase growth velocity, although some patients reported improved wellbeing and activity. The proportion of dietary energy supplied by protein fell significantly during supplementation. The evidence suggests that the reduced energy intake of children with chronic renal insufficiency is a related but not causal factor in their growth retardation.

Quantitative erfassung diskontinuierlicher ausscheidung und ihrer teilvorgänge in einer verformten kupferlegierung mit 1,5 Gew.-% Be

Discontinuous precipitation can be registered quantitatively in the temperature range 300–550°C. The number of cells is increased with increasing cold-rolling and decreasing temperature. The growth rate of the precipitation cells is decreased with increasing ageing-time t A , especially due to continuous precipitation. Deformation results in a lower growth velocity by a favoured continuous reaction. The sporadic abrupt falling-off in growth velocity and the corresponding break of the isothermal precipitation curves are due to a continuous precipitation of a dispersion also critical for strengthening. The kinetics of discontinuous reaction can be described by an equation of the type X = 1 − exp(− bt n A ) with n < 2. The volume fraction X increases with increasing annealing-time, owing to an increased growth velocity and decreases after cold-rolling up to ϵ = 20% according to a low growth-velocity. With greater deformation (30% ≤ ϵ ≤ 60%) the volume fraction X is increasing again—due to an additional nucleation of cellular precipitation.

LIPOATROPHY PRODUCED IN MICE AND RABBITS BY A FRACTION PREPARED FROM THE URINE FROM PATIENTS WITH CONGENITAL GENERALIZED LIPODYSTROPHY

Urine from 5 patients with congenital generalized lipodystrophy has been fractionated by protein precipitation and Sephadex gel filtration. A fraction with a molecular weight in the range of 1000 was observed to be metabolically active in mice, rats, and rabbits. Hypophysectomized rats got hypoglycaemia following an injection, and the lipolytic-hyperglycaemic effect of ACTH was reduced after injection into intact mice. This effect was probably due to insulin release, because no insulin-like activity was observed on isolated fat cells in vitro. Persistant changes were observed in the animals after 3 weeks of daily injections of the urinary fraction. Adult mice and rabbits developed lipoatrophy with decrease of body weight in spite of a doubling of the food consumption. The metabolic rate and the body temperature were raised. Infantile animals developed a lipodystrophic state with increased growth velocity, and 50 per cent increase of the body weight, although no fat depots were observed. The treated animals got hyperglycaemia, hypertriglyceridaemia, hyperinsulinaemia, and insulin resistance. The rabbits developed manifest diabetes. The corresponding fraction prepared from the urine from the lipoatrophic rabbits produced lipoatrophy after injection into the mice. It is suggested that the lipodystrophic urinary fraction is of hypothalamic origin, and that it acts through the pituitary gland. The fraction is still heterogenous, and was observed to contain thyrotrophin releasing activity.

TREATMENT OF PRECOCIOUS PUBERTY WITH CYPROTERONE ACETATE

Extract: Cyproterone acetate, an antiandrogenic steroid with inhibitory effects on gonadotropin secretion, was given to 13 girls and 6 boys with precocious puberty for periods of 1–3 years in a daily dose of 70 mg/m2 body surface area. Treatment was started at a mean chronologic age of 6.65 years in girls and 6.21 years in boys. No side effects were noted and the compound had a beneficial effect on the clinical signs of precocious puberty with the exception of increased growth velocity. Testicular size remained unchanged during treatment. In one boy high testosterone concentration in plasma was reduced to prepubertal levels. For analysis of the effect of treatment on growth the standard deviation score method was used. The data for height, bone age, height for bone age, and height prediction were compared with those obtained from 21 girls and 11 boys with precocious puberty who did not receive cyproterone acetate. No significant differences between treatment and control groups were found. It is concluded that cyproterone acetate in the dosage used is without effect on growth and would therefore be expected not to prevent short adult stature in patients with precocious puberty. Speculation: From the present study it is evident that cyproterone acetate at the dosage used does not diminish the rate of skeletal maturation, but that with other respects it is effective through its antiandrogenic and gonadotropin-inhibiting properties. This may indicate that in precocious puberty, bone maturation is more sensitive to the action of androgens and less suppressible than the secondary sex characteristics or behavioral changes. Whether earlier treatment and/or higher doses would also inhibit bone maturation remains uncertain.