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Biomedical subjects

Z Zadik

Publications and source records attributed to Z Zadik.

At least 55 records · Page 3Linked to original sources
PubMed1993

Coping and satisfaction with growth hormone treatment among short-stature children.

The ability of children to cope with a chronic medical problem requiring prolonged treatment has an effect on the quality of life of these children and of their parents and serves as an index of the quality of treatment. This study deals with coping ability and satisfaction with treatment of children whose stature was two or more SD below the average for age and gender. The study population included 96 patients, 53 of whom were male, who were on growth hormone (GH) treatment for at least 1 year. 65 patients were without any underlying disease, 15 had classical GH deficiency and 16 had Turner syndrome or renal disease. All patients were treated with daily injections at home from 12 to 66 months. Using a self-administered questionnaire, the ability to cope and the degree of satisfaction and compliance with treatment were assessed. No significant differences were found with respect to gender, the presence of an underlying disease, age at which treatment commenced or duration of treatment. Despite the fact that the outcome of GH treatment on final height has yet to be established, satisfaction and compliance were high.

Adaptation, Psychological↗
PubMed1993

The effect of exogenous and endogenous growth hormone on plasma growth hormone binding activity in prepubertal children.

To investigate the relationship between plasma growth hormone (GH) and plasma GH-binding protein (GHBP) activity we studied the effects of exogenous and endogenous GH on GHBP in children with a normal response to GH stimulation. The effect of exogenous GH on plasma binding activity was studied for 12 h after the administration of a subcutaneous GH bolus of 0.1 IU/kg and during the first year of GH therapy. The effect of endogenous GH secretion on GHBP was studied by measuring the integrated concentration (IC) of GH and GHBP over 24 h by means of a continuous blood withdrawal procedure. We also measured the GH and GHBP response to GH provocative tests. One hundred and two prepubertal children, 69 males, 33 females, age 8.8 +/- 2.2 years (mean +/- SD), were studied. Eighty-one were short, < 2 SDS for age and gender, and 21 were of normal height for age and gender. There was no difference in IC-GHBP between boys and girls. It correlated positively with age and body mass index (r = 0.802, p < 0.001 and r = 0.340, p < 0.001, respectively) but correlated negatively with ICGH (r = -0.412, p < 0.001) and with height velocity standard deviation scores (SDS, r = -0.355, p = 0.001). No correlation of ICGHBP with maximal GH response to provocative tests, insulin-like growth factor 1 levels, height in SDS or growth velocity after 1 year of GH therapy was found. During a provocative test there is an abrupt increase in GH but not change in GHBP.(ABSTRACT TRUNCATED AT 250 WORDS)

Carrier Proteins↗
PubMed1993

Serum concentrations and peritoneal loss of growth hormone and growth-hormone-binding protein activity in older adults undergoing continuous ambulatory peritoneal dialysis: comparison with haemodialysis patients and normal subjects.

Serum concentrations and peritoneal losses of growth hormone (GH) and of growth-hormone-binding protein (GH-BP) activity in 13 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) were compared with those of 13 patients on haemodialysis and 13 normal subjects. The individuals in the three groups were matched by age (40-83 years), gender, and serum glucose concentration. In addition CAPD and haemodialysis patients were matched by haematocrit, serum creatinine and albumin concentrations, and period of time on dialysis (0.5-127 months). GH in the serum and in the peritoneal effluent were measured by radioimmunoassay (RIA) and NB2 bioassay. GH-BP activity was analysed by binding assay and expressed as a percentage of the specific binding of GH. In the haemodialysis patients, serum GH was significantly greater and serum GH-BP activity significantly less than in the CAPD patients and control subjects. Between the two latter groups no significant differences in GH or in GH-BP activity were observed. GH bioactive/immunoactive ratios in the three groups were similar. Both GH and GH-BP were detected in the peritoneal effluent of CAPD patients, in whom an overnight (8-h) peritoneal loss of GH (8.0 +/- 1.4 x 10(-3) micrograms/h/1.73 m2) was strongly correlated with serum GH (r = 0.840). Circulating GH and GH-BP activity were influenced by serum creatinine and haematocrit. In addition a positive relationship was observed between GH-BP activity and body mass index and between GH and time on dialysis. These data reaffirm that older adults undergoing haemodialysis, unlike CAPD patients, exhibit persistent abnormalities in GH-GH-BP axis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1992

Integrated plasma cortisol concentration in children with asthma receiving long-term inhaled corticosteroids.

We assessed the effect of long-term therapy with inhaled beclomethasone dipropionate (BDP) on the pituitary-adrenal axis, by measuring the integrated concentration (IC) of plasma cortisol in eight children with asthma (age, 6-16 years) who regularly used inhaled BDP in doses ranging from 8 to 26.5 micrograms/kg (200-450 micrograms/day) for 6 months to 4 years. The control group included six children (age, 6-16 years) who had the IC of plasma cortisol measured as part of an endocrinological evaluation and were found to be healthy. Cortisol concentration was measured in blood samples collected continuously over a 24-hr period. Mean IC of plasma cortisol in the study group was significantly lower than in the healthy controls (mean +/- SD, 4.9 +/- 3.3 vs 9.1 +/- 1.9 micrograms/mL; P less than 0.02). Cortisol response to 0.25 mg ACTH (iv) was abnormal in one of the eight BDP-treated patients. No correlation was found between IC of plasma cortisol and the BDP dose, severity of asthma, height percentile, or the Tanner stage. We conclude that long-term therapy, even with relatively conventional doses of inhaled BDP may cause reduction in the normal physiological secretion of cortisol. The clinical relevance of low IC of plasma cortisol is not clear, but it may reflect partial suppression of the pituitary-adrenal axis.

Administration, Inhalation↗
PubMed1992

Changes in body composition of patients with subnormal spontaneous secretion of growth hormone, during the first year of treatment with growth hormone.

The effects of 1 year of growth hormone (GH) therapy were studied in 10 subjects with subnormal spontaneous secretion of GH, whose ages ranged from 6.5 to 12.4 years. Height, weight, body fat percentage, total body potassium (TBK), and extracellular water (ECW) were measured prior to initiating the treatment, and thereafter at 6 months (period 1) and 12 months (period 2). Height velocity almost doubled during the year of treatment: 7.8 +/- 0.8 and 7.1 +/- 0.7 cm/yr (P less than .0001) during periods 1 and 2, respectively, as compared with 3.9 +/- 0.6 cm/yr pretreatment. Body fat percentage decreased during period 1 to 18.2% +/- 4.9%, versus 16.3% +/- 4.5% (P less than .02), but stabilized thereafter (16.3% +/- 4.9%). Mid-arm muscle circumference (MAMC) and TBK increased in accordance with the predicted values for age. Body mineral density (BMD) increased both in absolute and standardized terms. No changes were found in ECW during treatment. We concluded that GH treatment in children with subnormal spontaneous secretion of GH has mainly a lipolytic effect on body composition, and that resistance to the lipolytic effect develops during the course of therapy.

Anthropometry↗
PubMed1992

Predictors of growth response to growth hormone in otherwise normal short children.

Sixty prepubertal short children (39 boys) with heights less than 2 SD for age and gender were treated daily for 1 year with recombinant human growth hormone (GH), either 0.1 IU/kg (group 0.1, n = 32) or 0.05 IU/kg (group 0.05, n = 28). Reserve of GH was determined by at least one GH provocative stimulus and 24-hour continuous blood withdrawal to determine the integrated concentration of GH (IC-GH). All participants had a GH response to provocative tests greater than 10 micrograms/L. The height velocity (mean +/- SD) of the group as a whole increased from 4.46 +/- 1.02 to 7.59 +/- 1.65 cm/yr (p less than 0.001). The growth velocity of group 0.1 was significantly greater than that of group 0.05 (8.1 +/- 1.5 vs 7.0 +/- 1.65 cm/yr; p less than 0.01). Bone age did not advance more than 1 year during the treatment period. Growth velocity after 1 year of GH therapy was inversely correlated with the IC-GH in both groups, as was the pretreatment height velocity. We found no correlation of growth velocity during GH therapy with other measures such as parental heights, bone age/chronologic age ratio, maximal GH response to provocative tests, chronologic age, or pretreatment insulin-like growth factor I levels. We conclude that the best predictors for the 1-year growth outcome of short children with a normal GH response to provocative tests are the pretreatment growth velocity and the IC-GH. The short-term benefit from GH therapy in children with a normal growth velocity and a normal IC-GH is poor, whereas marked growth acceleration is noted in children with a low growth velocity and a low 24-hour IC-GH.

Age Determination by Skeleton↗
PubMed1992

Final height after growth hormone therapy in peripubertal boys with a subnormal integrated concentration of growth hormone.

The aim of this study was to test the effect of growth hormone (GH) therapy on final height in peripubertal boys with idiopathic short stature in whom a subnormal integrated concentration of GH (< 3.2 micrograms/l) was found. Twenty-eight peripubertal children were studied. Height was below 2 SD for age, growth velocity was < 4.5 cm/year, bone age was more than 2 SD below mean for age and GH response to provocative tests was more than 10 micrograms/l. Eleven subjects (group B) were treated with recombinant GH 0.75 unit/kg/week, divided into 3 weekly doses for 2 years, and then the same weekly dose divided into daily injections was administered until final height was attained. Seventeen untreated children (group A) who were followed until cessation of growth served as controls. The GH-treated patients reached their target heights (-2.1 +/- 0.5, mean +/- SD in SDS) and predicted heights (-1.8 +/- 0.8) determined by the Bayley and Pinneau method, while the final heights of the untreated patients were significantly lower than their target heights and their predicted final heights (-2.7 +/- 0.7, -1.8 +/- 1.0 and -2.7 +/- 0.7, respectively). The main effect of GH was observed during the 1st year of treatment when height velocity was significantly higher in the GH-treated group than in the untreated one (9.3 +/- 2.1 vs. 5.3 +/- 1.1, respectively, p < 0.001). The high cost of the treatment in this specific age group should be weighed against the results.

Adolescent↗
PubMed1992

Effect of growth hormone therapy on IGF-I, bone GLA-protein and bone mineral content in short children with and without chronic renal failure.

Chronic renal failure (CRF) in the young is complicated by, among other conditions, growth retardation, hyperparathyroidism and uremic osteodystrophy. Many children with CRF are now being treated with growth hormone (GH). Since GH has a direct mitogenic effect on osteoblasts in culture, we studied the effects of GH therapy on osteoblastic activity, such as serum alkaline phosphatase (AP), bone GLA-protein (BGP) and bone mass density (BMD) in poorly growing children with and without CRF. Fifteen (4 girls, 11 boys) healthy children with short stature (SS) and 10 (3 girls, 7 boys) children with end-stage renal failure (CRF) 4.5-12.4 years of age were treated with daily subcutaneous injections of GH in a dose of 0.1-0.125 IU/kg/day for 1 year. IGF-I, BGP and BMD of the spine were determined before and after the year of treatment. During GH therapy, a similar increase in height velocity and IGF-I were noted in SS and CRF groups: 3.8 +/- 0.77 to 8.38 +/- 1.25 (p < 0.001) vs. 4.0 +/- 0.6 to 7.14 +/- 1.3 cm/year (p < 0.001) and 7.8 +/- 2.6 to 21.8 +/- 7.5 (p < 0.01) vs. 7.9 +/- 1.3 to 21.5 +/- 5.6 nmol/l (p < 0.01), respectively. AP increased from 205 +/- 27 to 274 +/- 50 IU/l (p < 0.01) in the SS group but not in CRF patients (223 +/- 58 pre- 218 +/- 51 IU/l post-GH therapy).(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗
PubMed1992

The diagnostic value of integrated growth hormone secretion studies shorter than 24 hours in normal- and short-growing children.

Spontaneous growth hormone (GH) secretion is evaluated by measurement of the 24-hour integrated concentration of GH (24-hour IC-GH), a major diagnostic procedure, or by shorter protocols such as monitoring 6 h during sleep. We have evaluated several possibilities for shortening the procedure by comparing the results of an abbreviated procedure to the 24-hour IC-GH studies. The study population consisted of 50 children with classic GH deficiency (group GHD), determined by provocative testing, and 45 children who had a subnormal secretion of GH (group N), determined by low 24-hour IC-GH but normal GH provocative tests. Twenty-two children of normal height and stature served as a control group. All the children were prepubertal, while there was no overlap between the lower 5th percentile of the 24-hour IC-GH of the control subjects (3.3 micrograms/l) and the upper 97th percentile of the 24-hour IC-GHs of the N and GHD groups (2.9 and 2.7 micrograms/l, respectively), there was a considerable overlap between the IC-GH of control subjects and that of the GHD and N groups measured in all the abbreviated blood withdrawal protocols, except for the 10-hour daytime and the 12-hour nighttime protocols of the GHD patients. It should be noted that there was only a small overlap between the control and the GHD groups during the 12-hour daytime protocol. We have found that the longer the blood collection period the greater the sensitivity and the specificity. We conclude that the 24-hour IC-GH test is the best diagnostic tool for identifying children with subnormal GH secretion.

Adolescent↗
PubMed1992

Enhanced response of human circulating erythroid progenitor cells to hGH and to IGF-I in children with insufficient growth hormone secretion.

The response of hematopoietic progenitors to the growth promoting effects of hGH and IGF-I has been documented. In this study, the effects of recombinant hGH and IGF-I on the growth of circulating erythroid burst forming cells (BFU-E) from growth-IGF-I retarded children with insufficient growth hormone secretion (IGHS) were evaluated and compared with values obtained from either children with short stature and normal growth hormone levels (SNGH) or normal donors. Both recombinant hGH and IGF-I had significantly greater stimulatory effects on the growth of BFU-E from the IGHS compared with the SNGH and with the normally growing children. At its optimal concentration of 200 micrograms/L, recombinant hGH had a stimulatory effect on the growth of BFU-E from 11 IGHS children yielding a mean +/- SD value of 2.0 +/- 0.3-fold above the unstimulated controls compared with 1.45 +/- 0.16-fold and 1.36 +/- 0.04-fold stimulation of BFU-E from six SNGH and five normal donors, respectively. Similarly, IGF-I, at its optimal concentration of 0.065 nmol/L (0.5 ng/mL), stimulated IGHS-derived BFU-E growth 1.67 +/- 0.25-fold above unstimulated controls, compared with 1.28 +/- 0.17-fold and 1.3 +/- 0.1-fold stimulation of BFU-E from SNGH and from normal donors, respectively. The hGH- and IGF-I-induced stimulatory effects could be neutralized by their respective specific MAb.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

The definition of a spontaneous growth hormone (GH) peak: studies in normally growing and GH-deficient children.

GH spontaneous peaks and their diagnostic utility have not been previously evaluated by means of a 24-h continuous withdrawal (CW) procedure in children with growth disorders. Using a CW pump, we studied the 24-h spontaneous secretion of GH in 129 prepubertal subjects grouped as follows. The control group (C) consisted of 20 children of normal height and growth rate. Group GHD consisted of 53 patients with classical GH deficiency (48 idiopathic and 5 organic). The NSD group consisted of 36 patients with a growth velocity below 4.5 cm/yr, normal GH response to provocative stimuli (PS), but a mean 24-h GH in the deficient range. Group NSS consisted of 20 short children with normal growth velocity, normal PS, and normal mean 24-h GH concentration. The mean GH levels for the 24-h period were 4.1 +/- 1.7, 1.4 +/- 0.5, 2.1 +/- 0.7, and 4.2 +/- 1.9, respectively, for the C, GHD, NSD, and NSS groups. For each subject, GH levels were determined in 48 0.5-h samples collected during the CW study, and the GH profile was analyzed by the Pulsar computer program. The mean number of peaks was 9.0 +/- 2.5 for C, 9.5 +/- 3.7 for GHD, 10.5 +/- 1.8 for NSD, and 9.5 +/- 3.2 for NSS. There was no statistical difference between groups. The mean amplitude of peaks was 9.8 +/- 8.9 for C, 1.6 +/- 1.0 for GHD, 2.9 +/- 1.3 for NSD, and 9.9 +/- 9.1 for NSS. Mean peak amplitudes in both GHD and NSD were significantly lower than in the C and NSS groups. The presence of peaks of more than 8 micrograms/L during the daytime (0800-2000 h) was a characteristic of children with normal integrated GH concentration (IC-GH) and was seen in 90% of normally growing children but in only 7% of poorly growing children with subnormal IC-GH. There was no significant difference in the number of pulses during the night between C and NSD groups. We conclude that differences in IC-GH between normally growing and poorly growing children are due to a lower amplitude of peaks during the daytime hours.

Adolescent↗
PubMed1992

Assessment of growth hormone (GH) axis in Turner's syndrome using 24-hour integrated concentrations of GH, insulin-like growth factor-I, plasma GH-binding activity, GH binding to IM9 cells, and GH response to pharmacological stimulation.

The GH axis was studied in Turner's syndrome (TS) patients. Thirty-seven prepubertal TS patients and 42 normally growing girls (NGG; 5.5-16.3 yr old), of whom 13 were prepubertal, were studied by 24-h continuous blood withdrawal and provocative tests. The 24-h integrated concentrations of GH (IC-GH), FSH (IC-FSH), and insulin-like growth factor-I (IC-IGF-I) as well as the IC-IGF-I/IC-GH ratio were determined. An increase in IC-GH with age and progression of puberty was found in NGG, but not in TS. IC-GH in the NGG was significantly higher than that in age-matched TS patients. Estrogen replacement therapy normalized IC-GH levels in 6 TS patients in whom these levels were subnormal for age. A positive correlation between IC-GH and IC-FSH or IC-estradiol was found in NGG (r = 0.462; P less than 0.01), but not in TS patients. The IC-IGF-I/IC-GH ratio was significantly higher in the TS than in the NGG group. Serum GH-binding activity and serum GH binding to IM9 cells in the TS group did not differ from those in the normal group. We hypothesize that the growth retardation of TS results from a combination of insufficient GH secretion, mainly due to sex steroid deficiency, and an end-organ resistance to IGF-I. IGF-I receptor studies are needed to test this speculation about IGF-I resistance.

Adolescent↗
PubMed1991

Age-related patterns of thyroid-stimulating hormone response to thyrotropin-releasing hormone stimulation in Down syndrome.

Thyroid function in subjects with Down syndrome was studied using the thyrotropin-releasing hormone test. Forty-seven infants and children with Down syndrome were investigated. Ages ranged from 1 month to 7 years; there were 26 boys and 21 girls. Fourteen of the subjects with Down syndrome who had an exaggerated thyroid-stimulating hormone response to thyrotropin-releasing hormone stimulation had two or more annual follow-up tests. The remaining 33 subjects who only underwent one thyrotropin-releasing hormone test were compared with 22 age-matched controls (11 boys and 11 girls). Mean basal thyroxine 4 and triiodothyronine 3 values were in the normal ranges. All thyroid antibody titers were negative. Mean basal thyroid-stimulating hormone levels of subjects with Down syndrome were significantly higher than those of controls for all ages, even though there was a decline in thyroid-stimulating hormone levels in both groups. Peak thyroid-stimulating hormone response levels were significantly greater in the subjects with Down syndrome than in the controls. Longitudinal study of the 14 children with Down syndrome with an exaggerated thyroid-stimulating hormone response showed that the response remained exaggerated until the third year of life, when it declined to normal levels. Thyroid dysfunction during the growth spurt of infancy or delayed maturation of the hypothalamic pituitary thyroid axis are proposed mechanisms.

Analysis of Variance↗
PubMed1991

Chronic growth hormone administration does not suppress endogenous growth hormone secretion in patients with neurosecretory growth hormone dysfunction.

Short children who respond normally to growth hormone (GH) stimulation, but have a subnormal spontaneous secretion of GH (neurosecretory GH dysfunction, NSD) are treated with exogenous GH which might suppress their endogenous GH secretion. The effect of chronic administration of GH (8-24 months) on plasma GH responses to GHRH, clonidine and spontaneous GH secretion were studied in 17 NSD patients. The diagnosis of NSD was based on a normal GH response to clonidine (greater than 10 micrograms/l) and an integrated concentration of (IC-GH) GH less than 3.2 micrograms/l. The GH dose used in this study was 0.25 IU/kg three times a week in 10 patients and 0.05 IU/kg daily in 7 patients. Insulin-like growth factor I levels (nmol) increased significantly on therapy from 9.3 +/- 3.8 to 24.4 +/- 22.4 (p less than 0.001). The GH response (microgram/l) to GHRH was 20.4 +/- 5.5 before treatment and 22.4 +/- 6.2 on GH. Peak GH after clonidine was 22.4 +/- 8.9 and 22.8 +/- 8.1, respectively. There was no significant decrease in the number of GH spontaneous peaks (1.8 +/- 0.7 vs. 2.0 +/- 0.7, respectively) or in the area under the curve. A subcutaneous GH bolus of 0.25 IU/kg in 4 patients resulted in a GH peak of 55-82 micrograms/l at 3-5 h and a gradual return to basal levels at 15-20 h after GH administration. The first spontaneous GH peak appeared 26-28 h after GH injection, peak amplitude was 10-15 micrograms/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Determination by Skeleton↗
PubMed1991

Human growth hormone and insulin-like growth factor-1 enhance the proliferation of human leukemic blasts.

As the number of long-term survivors of childhood leukemia increases, growth retardation has emerged as a significant complication. Treatment of these children with growth hormone (GH) has been suggested and sporadically implemented. We, therefore, studied the effect of human GH (hGH) and its by-product insulin-like growth factor-1 (IGF-1) on the growth of leukemic cells in vitro. Under serum-free conditions hGH and IGF-1 induced a significant dose-dependent proliferative effect on promyelocytic leukemia (HL60) and Burkitt's lymphoma (Daudi) cell lines. Anti-hGH antibodies negated the stimulatory effect of hGH and anti-IGF-1 serum abrogated the growth-promoting effect enhanced by IGF-1. Similar statistically significant stimulatory properties were found when freshly obtained marrow cells from four of five acute lymphoblastic leukemia (ALL) of childhood and four acute myelogenous leukemia (AML) patients were studied in ALL and AML blast-cell clonogenic assays. ALL colonies increased numerically by 72% (P less than .025) and AML colonies by 92% (P less than .01) in the presence of hGH at concentrations of 2.5 x 10(2) and 3.0 x 10(2) ng/mL, respectively. IGF-1 stimulated ALL and AML blast-colony growth at concentrations ranging from 0.05 to 0.5 ng/mL by up to 105% (P less than .025) and 65% (P less than .03), respectively. Our in vitro data suggest that circulating hGH and IGF-1 may promote leukemic blast cell replication in vivo, and the supplemental administration of hGH to leukemia patients in remission must be carefully monitored for early relapse.

Bone Marrow↗