Biomedical subjects

Z Zadik

Publications and source records attributed to Z Zadik.

At least 73 records · Page 4Linked to original sources

PubMed1991

Twenty-four-hour profile of plasma growth hormone-binding protein.

In experimental animals each burst of GH pulse is followed by a wave of receptor turnover and an increase in serum GH-binding protein (GH-BP), which occurs 60 min after the GH peak. The present report describes the 24-h profile of plasma GH-BP and its correlation to GH pulsatility in normal individuals. Four normally growing children in early puberty were the subjects of this study. Blood was withdrawn continuously for 24 h in 30-min fractions. Pulse analysis of both GH and GH-BP was performed by the Pulsar program. The vast majority of the GH pulses were accompanied by GH-BP pulses within 30 min. Correlation of plasma GH levels to GH-BP levels on the residual series above the smoothed baseline of all 172 individual samples was r = 0.447 (P less than 0.001). Thus, plasma GH-BP levels fluctuate rapidly in relation to the pulsatility of plasma GH levels. This may influence the GH disappearance rate and brings into question some of the deconvolution calculations of GH secretory impulses.

Carrier Proteins↗

PubMed1991

Seasonal variation in growth during growth hormone therapy.

Seasonal variation in growth of normal children has been well described, although the mechanism by which it occurs has not been elucidated. The growth of 52 growth hormone-deficient children treated with synthetic human growth hormone was analyzed. A similar seasonal variation was observed, with mean (+/- SEM) peak growth occurring in the summer (8.2 +/- 0.3 cm/y) and winter (7.7 +/- 0.2 cm/y), and trough growth occurring in the autumn (6.9 +/- 0.3 cm/y). Forty-seven percent of subjects grew minimally during the autumn, and only two children showed peak growth in that season. Individual variations between maximal and minimal growth seasons amounted to 3.5 +/- 0.3 cm/y. The seasonal pattern was statistically significant for the group as a whole, for the prepubertal subgroup, and for the boys. The variation persisted when the first year of treatment was excluded to avoid bias of the initial growth spurt. The season of onset of therapy did not affect total growth during the first year. The demonstration of a seasonal pattern in growth of these children suggests that the seasonal variation may be mediated by peripheral rather than central factors. Paired clonidine-provoked growth hormone levels and an integrated concentration of 24-hour growth hormone levels and serum levels of insulinlike growth hormone I measured in a control group of normally growing children were also analyzed and showed no seasonal variation. This further suggests that peripheral rather than central factors are responsible for the seasonal variation in children's growth.

Adolescent↗

PubMed1990

Assessment of growth hormone secretion in normal stature children using 24-hour integrated concentration of GH and pharmacological stimulation.

The integrated concentration of serum GH (IC-GH) is used for the assessment of spontaneous GH secretion. In order to use the IC-GH as a diagnostic tool a normative reference range needs to be established. We determined the IC-GH by continuous blood withdrawal in 119 children of normal height, weight and growth rate. Although the mean IC-GH increased with pubertal status, 4.4 +/- 1.2 micrograms/L at Tanner I (n = 36), 5.5 +/- 2.1 micrograms/L at Tanner II-III (n = 43), and 5.8 +/- 1.6 at Tanner IV-V (n = 40) (P less than 0.03), there was a considerable overlap of individual IC-GH levels between the pubertal groups. Gender affected the mean IC-GH level slightly, but not the range. Although the mean IC-GH of girls tended to be higher than that of boys this difference was not statistically significant. Ninety five percent of the IC-GH values were above the 3.2 micrograms/L level. The response to pharmacological stimulation (clonidine, insulin, or arginine) was also evaluated in 68 of the subjects. The peak GH response to pharmacological stimulation (micrograms/L) with clonidine 21.0 +/- 10.7 (n = 66) was significantly higher than to either arginine 13.1 +/- 6.1 (n = 23) or insulin 14.2 +/- 6.3 (n = 19) (P less than 0.01). The peak response to clonidine increased significantly with pubertal status (P less than 0.001) and there was an interactive effect of gender and pubertal stage where the GH response of prepubertal boys exceeded that of prepubertal girls but the response of pubertal girls exceeded that of pubertal boys (P less than 0.02). The peak stimulated GH levels was correlated with IC-GH in this subgroup r = 0.52, P less than 0.0001). This study provides a large normative data base for IC-GH and the GH provocative tests in normally growing children of varying pubertal status.

Adolescent↗

PubMed1990

Hypocortisolemia in children undergoing evaluation for growth hormone deficiency.

The group of children who have clinical manifestations of GH deficiency may potentially contain a large number of patients with secretory defects of cortisol. We assessed physiological cortisol secretion by measuring the 24-h integrated concentration of cortisol (IC-F) in a series of 105 patients, aged 7-19 yr, undergoing endocrinological evaluation for growth impairment possibly due to GH deficiency. The reference value for IC-F, established from 30 normal stature, normal weight children (controls), aged 7-18 yr, was 157 +/- 41 nmol/L (mean +/- 1 SD). There was no effect of age, gender, or pubertal status on IC-F in controls. The IC-F of patients was 150 +/- 72 nmol/L. Twelve patients (11%) had IC-F values more than 2 SD below the mean (i.e. less than 75 nmol/L) of the controls (P less than 0.001). An IC-F below 75 nmol/L was associated with a blunted peak cortisol response to insulin-induced hypoglycemia (367 +/- 160 nmol/L compared to 464 +/- 155 nmol/L in the other patients; (P less than 0.05). None of the patients had obvious clinical symptoms of hypocortisolemia at the time of testing. In general, IC-F levels were not correlated with IC-GH. However, 10 patients who had subnormal IC-F values also had laboratory evidence of GH secretory defects; 7 had subnormal IC-GH levels but normal stimulated GH responses, and 3 had both subnormal responses to stimulation as well as subnormal IC-GH. The long term prognosis and management implications of hypocortisolemia diagnosed in this patient group require further evaluation.

Adolescent↗

PubMed1990

Reproducibility of growth hormone testing procedures: a comparison between 24-hour integrated concentration and pharmacological stimulation.

The purpose of this study was to compare the reproducibility of two approaches to the evaluation of GH secretion: the integrated concentration of GH (IC-GH), a physiological test of GH secretion, and pharmacological stimulation tests. IC-GH was determined in 40 poorly growing children twice within 4 weeks. The first and second IC-GH were highly correlated r = 0.859, P less than 0.001. One hundred and thirteen poorly growing children underwent pharmacological GH stimulation tests twice within 6 weeks. A moderate correlation was found between the first and second pharmacological test r = 0.524, P less than 0.01. Among the three pharmacological stimuli studied, clonidine (n = 81) had the highest reproducibility followed by arginine (n = 20), and insulin (n = 12). We conclude that IC-GH is more consistently reproducible than the GH response to repeated pharmacological stimulation.

Adolescent↗

PubMed1989

Incidence of neurosecretory dysfunction among children aged 6-14 years in Rehovot, Israel.

Screening of 7500 children aged between 5.8 and 14.4 years, out of a total population of 39,690 in this age group in the Rehovot region, revealed 111 children with heights 2.5 SD below the mean for their age, according to the Tanner-Whitehouse standards. Included among these short children were eight with hypochondroplastic skeletal disease, two with Down's syndrome, four with thalassaemia, four with Turner's syndrome, three with coeliac disease, four with classical growth hormone (GH) deficiency, four with intrauterine growth retardation, four with systemic disease and 78 without obvious underlying causes. In 35 of the 78 children in the last group, the 24-hour integrated concentration of GH was in the hypopituitary range (less than 3.2 ng/ml), and GH neurosecretory dysfunction (NSD) was accordingly diagnosed. This represents an incidence of GH neurosecretory dysfunction of 45% among abnormally short children without underlying pathology, and is consistent with the authors' previous findings. The overall frequency of GH neurosecretory dysfunction in the screened population was 4/1000.

Adolescent↗

PubMed1989

Somatotropin as measured by a two-site time-resolved immunofluorometric assay.

To date, many of the current criteria for diagnosis of somatotropin (growth hormone, GH) deficiency have been based upon measurement of this hormone by competitive radioimmunoassay (RIA) with use of polyclonal antibodies. In recent years, however, the development of hybridoma technology has led to the generation of various monoclonal antibodies (Mabs) to GH with different affinities and epitope specificities. Subsequently, these reagents have been used in the development of noncompetitive two-site immunometric assays (e.g., immunoradiometric assay; IRMA). In general, the values obtained for serum GH by IRMA have been lower than those obtained by RIA, because of the epitope-specificity profile of the Mabs in the IRMA. Attempting to obtain GH values numerically similar to those by RIA, we used a combination of Mabs to GH in developing and evaluating a two-site time-resolved immunofluorometric assay (IFMA) based on the streptavidin-biotin interaction. Fluorescence is proportional to concentration of analyte and is linearly related to concentration over the range 0.3 to 40 micrograms/L. The assay was satisfactory with respect to sensitivity, accuracy, and precision (CV less than 10% over the entire working range). In addition, the concentration of GH was determined by the IFMA and a competitive RIA in serum obtained from GH deficient and acromegalic patients. The pairing of antibodies in the IFMA gave numerical values that agreed well with those by RIA (r = 0.97; n = 100).

Acromegaly↗

PubMed1988

Growth hormone (hGH) secretion and turnover in three patients with Laron-type dwarfism.

The 24-h secretory pattern of hGH was studied by the aid of a continuous blood withdrawal pump in three Laron-type dwarfism (LTD) patients and compared with that in sex- and age-matched normal control subjects. It was found that the secretion of hGH was enhanced in the LTD patients, but in all three the diurnal secretory profile, as expressed by the number of pulses and the sleep-related maximal pulse, was preserved. In the younger LTD patients, women aged 19 and 21 years, the number of pulses was 9 and 7 (compared with 6 in the control subjects), the maximal hGH pulse amplitude was 164 and 280 ng/ml (compared with 135 ng/ml), the area under the curve (AUC) was 560 and 780 (compared with 268), and the average integrated concentration (A-IC) of hGH was 33.9 and 23.4 ng/ml (compared with 11.3). In the older LTD patient, a man aged 27 years, the hGH secretion was lower than that in the LTD women, but still higher than that in normal matched controls: the number of pulses was 4 (control 2), maximal pulse amplitude 67 ng/ml (control 19), AUC 231 (control 51), and A-IC 9.9 ng/ml (control 2.2). The decline in hGH secretion, which is characteristic of advancing age in normal subjects, seems to occur in LTD as well. Metabolic clearance rate (MCR) and production rate (PR) of hGH were measured in the 19-year-old female LTD patient. Her MCR was 73.4 ml/m2 per min, and her PR was 2,480 ng/ml compared with 158.3 and 839, respectively, in a normal subject. The exaggerated PR explains the elevation of plasma hGH in this syndrome and is probably the result of a lack of negative feedback due to insulin-like growth factor deficiency.

Adolescent↗

PubMed1987

Blood pressure determinations in Israeli schoolchildren aged 5 to 14 years.

Blood pressure (BP) determinations were made by three physicians in 1,554 healthy Israeli schoolchildren aged 5 to 14 years, of whom 783 wer boys and 771 were girls. Subjects were divided into four groups according to ethnic origin: Yemenite--560, North African--357, Iraqi-Iranian--246, and European-American--391. There were no statistically significant differences in either systolic (S) or diastolic (D) BP between ethnic groups or between sexes. Comparing our data with those compiled by the United States Task Force on Blood Pressure Control in Children, we found that the SBP tended to be lower than in American children by about 10 mm Hg, while the DBP was lower by about 7 mm Hg. An additional 4,460 children were examined by public health nurses, and 25 (0.6%) children were found to have a DBP above the 97th percentile for their age, and 46 (1.0%) children were found to have an SBP above the 97th percentile for their age. None of the children had an SBP or DBP exceeding the mean for their age by 2.5 SD, nor had any child any sign or symptom of high BP. Based on these results, we doubt the usefulness and cost-effectiveness of BP screening of children.

Adolescent↗

PubMed1986

Detection of primary aldosteronism by the 6-hour integrated aldosterone/renin ratio.

An outpatient diagnostic procedure measuring the 6-hour integrated plasma concentration of aldosterone and plasma renin activity was used to detect primary aldosteronism in 12 patients with low renin hypertension, including six with mild hypertension and normal urinary excretion and spot plasma levels of aldosterone. The ratio of integrated plasma concentration of aldosterone to plasma renin activity in the 12 patients (mean, 339; range, 116-700; p less than 0.0001) did not overlap with that measured in 105 normotensive controls (mean, 27.8; range, 5-97) or in 87 subjects with essential hypertension (mean, 29.2; range, 4-67). Eight patients had surgically proven adenomas (3 of which measured less than 5 mm) with normalization of blood pressure following adrenalectomy. The four remaining patients had bilateral hyperplasia. The 6-hour integrated plasma concentration of aldosterone to plasma renin activity ratio was found to be a useful new outpatient diagnostic tool for evaluation of primary hyperaldosteronism.

Adenoma↗

PubMed1986

Requirement of mineralocorticoid in congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency.

Marginal salt loss occurs in patients with congenital adrenal hyperplasia due to 11 beta-hydroxylase (11-OHase) deficiency treated with dexamethasone and is accompanied by increased PRA. The present study was undertaken to evaluate the effect of the stimulated renin-angiotensin system on pituitary-adrenal suppression. Seven patients with 11-OHase deficiency were subjected to a series of treatments with dexamethasone, cortisol, and combined cortisol and 9 alpha-fluorohydrocortisone. The latter combination suppressed PRA and sodium excretion, and produced better control of the pituitary-adrenal axis, as measured by plasma ACTA and serum 11-deoxycortisol. We conclude that in children with 11-OHase deficiency, PRA needs to be monitored, and when it is elevated, mineralocorticoid replacement is indicated.

Adolescent↗

PubMed1985

Pseudotumor cerebri in a boy with 11-beta-hydroxylase deficiency--a possible relation to rapid steroid withdrawal.

A boy who was known to suffer from adrenogenital syndrome due to 11-beta-hydroxylase deficiency was treated with appropriate steroid replacement, which fully compensated for the deficiency. An intercurrent febrile illness with anorexia and vomiting necessitated an abrupt discontinuation of steroids. He presented with classic signs of pseudotumor cerebri 3 days following steroid withdrawal. Our studies imply that a combination of steroid withdrawal and dehydration with increased sodium urinary excretion, caused rapid fluid shifts within the brain, resulting in intracranial hypertension. At present, when a considerable number of children are on long-term steroids for various reasons, pseudotumor cerebri should be considered in the list of complications during abrupt steroid withdrawal.

Adrenal Hyperplasia, Congenital↗

PubMed1985

The influence of age on the 24-hour integrated concentration of growth hormone in normal individuals.

We examined changes in spontaneously secreted growth hormone with aging by studying the 24-h integrated concentration of GH (IC-GH) of 173 nonobese subjects (height, greater than or equal to 5%; 7-65 yr of age). There was no significant difference in IC-GH on repeat testing of 13 men or in 23 women studied in the follicular and again in the luteal phase of the menstrual cycle. The level of IC-GH was strongly effected by age; children had the highest mean IC-GH, and there was a decline in IC-GH with increasing age after the second decade of life. The correlation of IC-GH with age was highly significant (r = 0.73; P less than 0.0001). There was no difference in IC-GH between males and females when matched for age. The mean IC-GH at Tanner stage 5 of puberty (7.4 +/- 2.0 ng/ml) was higher than that at stages 2-4 (5.7 +/- 1.4; P less than 0.0005) or that in prepubertal children (5.8 +/- 1.4; P less than 0.001). Thus, age and pubertal status must be carefully considered when interpreting the IC-GH for patients suspected of having deficient or excessive secretion of GH.

Adolescent↗

PubMed1985

The diagnostic value of the 24 hour integrated concentration of plasma aldosterone.

The 24-hour urinary excretion rate of aldosterone, the 24-hour integrated concentration of plasma aldosterone (IC-ALDO) and the morning plasma aldosterone levels from a single, discrete venipuncture of 92 subjects (30 normal subjects, 62 patients with mild, essential hypertension) were compared, using the variance ratio method, to 12 patients with primary aldosteronism. The variance of the IC-ALDO was significantly lower than the respective variances of the 24-hour urinary excretion of aldosterone (P less than 0.01) and of the discrete, morning plasma levels of aldosterone (P less than 0.01). The clinical usefulness of this diagnostic procedure depends on its ability to discriminate between healthy subjects and various hypertensive patients. Because of its narrower variance and enhanced discriminatory ability, the 24-hour IC-ALDO may have useful application in diagnosis of various disorders of aldosterone secretion. We have found the IC-ALDO completely separated 11 of 12 primary aldosteronism patients (mean 36 +/- 17) from essential hypertensive controls (mean 9.6 +/- 4.1) (P less than 0.01). When IC-ALDO was combined with integrated concentration of plasma renin activity in an ALDO/RENIN ratio, all 12 primary aldosteronism patients were diagnosed.

Adolescent↗

PubMed1985

Do short children secrete insufficient growth hormone?

The 24-hour integrated concentration of growth hormone from 46 children of normal stature was compared with that of 90 short children. Nineteen of the short children had classic growth hormone deficiency by standard pharmacologic growth hormone stimulation tests. Seventy-one children had normal growth hormone responses to stimulation. The mean integrated concentration of growth hormone for children with normal stature (6.6 +/- 1.9 ng/mL) was greater than the mean value for those with normal stimulated growth hormone (3.8 +/- 2.3 ng/mL) and greater than the mean value for those with growth hormone deficiency (1.6 +/- 0.6 ng/mL); differences between groups were all statistically significant (P less than .0001). Forty-five percent of children with normal stimulated growth hormone responses had integrated concentration of growth hormone within the range of values for the group with growth hormone deficiency; this finding may provide the explanation for their poor growth. Thus, patients with normal growth hormone responses have a spectrum of spontaneous growth hormone secretion ranging from normal to impaired. Recent reports indicate that children with normal growth hormone responses who have very low integrated concentration of growth hormone may have the potential to improve their growth with growth hormone therapy. Therefore, use of the integrated concentration of growth hormone may be a more effective method than standard pharmacologic stimulation tests for determining which short children are potentially able to respond to growth hormone therapy.

Adolescent↗

PubMed1984

The effect of serum growth factors and xyloside on molecular aging of proteoglycan in embryonal chick cartilage.

The effects of normal human serum, insulin-like growth factor and beta-D-xyloside on the synthesis of proteoglycan, as well as their differential effect on the synthesis of chondroitin sulfate and keratan sulfate side-chains, were studied in chick embryonal cartilage. The glycosaminoglycans found in the incubation medium were mainly intact carbohydrate moieties of partially degraded proteoglycan molecules, whereas the tissue-bound glycosaminoglycans were of intact proteoglycan molecules. In incubations with normal human serum, the synthesis of the chondroitin sulfate side-chains of the tissue-bound glycosaminoglycans was preferentially stimulated, while the percentage of medium glycosaminoglycan (out of the total glycosaminoglycan in tissue and medium) was reduced, compared to control incubations. In incubations with insulin-like growth factor, the synthesis of the keratan sulfate side-chains of the tissue-bound glycosaminoglycan was preferentially stimulated, whereas the percentage of the medium glycosaminoglycan resembled that of control incubations. In incubations with xyloside, a marked reduction of tissue-bound glycosaminoglycan was noticed, mainly of chondroitin sulfate chains, and only a slight decrease in keratan sulfate chains. Human serum of various age groups stimulated proteoglycan synthesis in embryonal chick cartilage to almost the same extent. However, sera from babies and adults were found to stimulate chondroitin sulfate chains preferentially, whereas serum of aged subjects preferentially enhanced the synthesis of keratan sulfate chains. These findings suggest that the synthesis and/or degradation of the various types of glycosaminoglycan chains (chondroitin sulfate and keratan sulfate) of cartilage proteoglycan can be regulated differentially by serum growth factors. Secondly, the growth hormone-mediated serum factor (insulin-like growth factor) seems to play a role in molecular aging of proteoglycans.

Adolescent↗

PubMed1984

Salt loss in congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency.

Nine patients with 11 beta-hydroxylase deficiency had 13 episodes of gastroenteritis requiring hospital admission and fluid administration. Eight episodes were accompanied by hyponatraemia and salt loss. The salt losing patients were treated with excessive glucocorticoid and those with normal serum sodium concentrations were treated with inadequate glucocorticoid. Excessive glucocorticoid suppressed deoxycorticosteroid secretion, resulting in salt loss.

Adrenal Hyperplasia, Congenital↗

PubMed1984

Salt loss in hypertensive form of congenital adrenal hyperplasia (11-beta-hydroxylase deficiency).

Studies in patients with congenital adrenal hyperplasia due to 11-hydroxylase deficiency (11-OHD) suggest a common defect in the adrenal zona fasciculate and zona glomerulosa. The hypertension in untreated 11-OHD patients is considered to be secondary to the accumulation of deoxycorticosterone as a consequence of inadequate 11-beta-hydroxylation in the biosynthesis of aldosterone, and is alleviated by glucocorticoid suppression. To investigate whether deoxycorticosterone suppression in these patients resulted in loss of salt, 11 patients with 11-OHD aged 4-26 yr were studied. Patients were evaluated during dexamethasone suppression (0.6 mg/m for 2 weeks) while receiving a normal diet and a low salt diet (10 meq Na/24 h). There was no significant change in serum electrolytes, cortisol, 11-deoxycortisol, and DOC during these two dietary regimens. PRA in the recumbent and upright positions on both diets was significantly higher in the patients than in normal subjects. Plasma or urinary aldosterone levels were significantly lower in the 11-OHD patients than in the normal controls. Moderate salt loss occurred during the low salt diet. It is concluded that sodium retention is incomplete in glucocorticoid-treated 11-OHD patients. Partial sodium retention is maintained by increased PRA and a subnormal aldosterone response. 11-OHD patients should be carefully monitored during acute disease states and, when electrolyte imbalance is suspected, treatment with mineralocorticoid should be considered.

Adolescent↗