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Biomedical subjects

Z Zadik

Publications and source records attributed to Z Zadik.

At least 37 records · Page 2Linked to original sources
PubMed1997

Extracorporeal losses of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in adult patients on CAPD.

The effects of extracorporeal (urinary plus peritoneal) losses of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) on their respective serum levels were studied in 10 adult patients (aged 42-74 years) with end-stage renal failure and residual renal function of 0-4.5 mL/min. All patients had been on continuous ambulatory peritoneal dialysis (CAPD) for a period of 2-27 months. Morning serum, 24-hour urine, and 8-hour overnight peritoneal concentrations of IGF-I and IGFBP-3 were measured by radioimmuno- (Incstar) and immunoradiometric (Active) assays. CAPD patients showed extracorporeal losses (mean +/- SEM) of 118.7 +/- 10.6 micrograms (urinary 6.4 +/- 2.8 and peritoneal 112.3 +/- 8.5 micrograms) of IGF-I/24 hour and 1.5 +/- 0.1 mg (urinary 0.2 +/- 0.1 mg and peritoneal 1.3 +/- 0.1 mg) of IGFBP-3/24 hour. Extracorporeal losses of IGF-I accounted for about 4% of the daily production rate of this polypeptide, and the peritoneal and urinary concentrations of IGFBP-3 did not exceed 4% and 14%, respectively, of their serum levels. Serum concentrations of IGF-I (227.7 +/- 64.2 micrograms/L) and IGFBP-3 (5.3 +/- 2.4 mg/L) were not significantly correlated with extracorporeal, peritoneal, or urinary losses of these proteins or with residual renal function. We suggest that extracorporeal losses of IGF-I and IGFBP-3 in adult patients on CAPD do not influence their serum levels and that IGF-I may therefore be used as a marker of malnutrition.

Adult↗
PubMed1996

Final height prediction models for pubertal boys.

Accurate adult height prediction is of clinical importance in assessing the need for pharmacological intervention and in the evaluation of the outcome of therapy. The methods currently in use are subject to a wide range of error, one source of which is the use of bone age (BA) measurements. We have developed a computer model for predicting adult height in pubertal boys without using BA determinations. The model is based on the existing Infancy-Childhood-Puberty model and calculates the onset of the pubertal growth spurt. Predicted adult height was assessed using this new model and four others in a group of normal boys and in a group of short normal boys receiving growth hormone. Calculated final heights by all the methods were not significantly different. Incorporation of paternal height into the prediction equations increased the accuracy of the prediction. It was concluded that our new model is as accurate as existing methods of predicting final height that involve assessing BA.

Adolescent↗
PubMed1996

Vitamin A levels and growth hormone axis.

Vitamin A (VA) is required for normal growth and development retinoic acid may be the active metabolite through binding to nuclear receptors. Recently a correlation between nocturnal growth hormone (GH) secretion and VA was was found in short slowly growing children. We determined the 24-hour integrated concentration of GH (IC-GH), GH response to provocative stimuli, IGF-I, IGF-binding protein-3 (IGF-BP3) and GH-binding protein (GH-BP) in 34 prepubertal children (25 m/9 f) 5-10 years of age, height -2.5 to 1.5 SDS and body mass index -1.5 to 1.5 SDS for age and sex. Since folic acid, vitamin B12, IGF-I, cholesterol, triglycerides and VA carrier proteins were normal we assumed that no major nutritional deficiency existed. The correlation matrix of the variates tested were p < 0.05 for VA and IC-GH and p < 0.006 for IGF-BP3. It is suggested that VA might have a direct affect on both ICGH and IGF-BP3.

Carrier Proteins↗
PubMed1996

Growth of short children during and after discontinuation of growth hormone therapy.

We have attempted to evaluate the relationship between spontaneous growth hormone (GH) secretion and the response to GH therapy as well as the effect of discontinuation of GH therapy on further growth. The 24-h integrated concentration of GH (ICGH) was determined in 150 short children (< 2 SD for age) with a GH response to clonidine stimulation of more than 10 mcg/L. The patients were treated with GH for 4 yr and were observed for 1 yr following cessation of GH treatment. Twenty-two out of 52 patients who had an ICGH of less than 3.2 mcg/L (group LICGH) and 28 out of 60 patients who had an ICGH of more than 3.2 mcg/L (group NICGH) were followed without GH therapy. Only patients who remained prepubertal throughout the study were included in the analysis. The growth response of the LICGH to GH was better than that of the NICGH children. Patients regained normal growth velocity 6-12 months after discontinuation of GH therapy. Three children of the LICGH subsequently developed classic GH deficiency. These studies demonstrate that short-term GH therapy can improve the growth channel. Children with a low ICGH grow better on GH than children with a normal ICGH. Children with a low ICGH need continued observation and retesting when growth velocity is low.

Body Height↗
PubMed1996

A prospective pilot study of co-treatment with growth hormone and gonadotropins for improving spermatogenesis in normogonadotropic patients with severe oligoteratoasthenospermia.

The objective of this study was to induce spermatogenesis by co-treatment with growth hormone and gonadotropins in normogonadotropic patients with severe oligoteratoasthenospermia (OTA) who had failed to respond adequately to conventional therapy. A prospective study in which co-treatment with growth hormone (4 IU) and human menopausal gonadotropin (hMG; 150 IU of follicle-stimulating hormone (FSH) and 150 IU of luteinizing hormone (LH)), three times a week, and human chorionic gonadotropin (hCG; 2500 IU), two times a week for 24 weeks, were administered after unsuccessful treatment for at least 12 weeks with gonadotropins. Four patients who had failed to respond to conventional treatment with gonadotropins participated in the study. Semen volume, sperm production, serum testosterone, LH, FSH, insulin-like growth factor-I (IGF-I) and growth hormone-binding protein concentrations were used to measure outcome. In all four patients, there was no improvement in sperm quality as compared to baseline measurements. Serum testosterone concentrations remained within normal limits. A significant increase in both serum IGF-I and growth hormone-binding protein was found following treatment with growth hormone. Our results do not encourage the use of co-treatment of gonadotropins with growth hormone in cases of normogonadotropic OTA syndrome patients who fail to respond adequately to the conventional therapy with gonadotropins.

Adult↗
PubMed1995

Effect of growth hormone treatment on quality of life of short-stature children.

While enhanced growth velocity is a well-established benefit following the initiation of growth hormone treatment (GHT), the potential benefit of GHT on quality of life (QOL) of short-stature children has not yet been documented. We compare QOL of two groups of short-stature children who attended the Endocrine Unit (EU) and were 2 SD or more below the average for age and gender. The first group included 96 patients of whom 65 were without any underlying disease, 15 had classical GH deficiency and 16 had Turner syndrome or renal disease. These patients were on GHT for at least 2 years. The other group included 33 patients. Owing to lack of resources to include these 33 patients in a clinical trial, they did not get GHT. They were normal variant of short stature, and their height was similar to the height of the 65 children included in the first group. QOL was assessed using self-administered questionnaires, which were filled out by the patients on their regular visit to the EU. QOL was defined in terms of school achievements, leisure activities, emotional and physical self-esteem, relationships with peers and family members. No significant differences were found between the two groups. The mean scores for the different domains of QOL ranged between 2.6 and 3.8 on a scale ranging from 1 (very pessimistic view) to 4 (very optimistic view).

Adolescent↗
PubMed1995

Insulin-like growth factor-I in patients on CAPD and hemodialysis: relationship to body weight and albumin level.

The relationship between insulin-like growth factor-I (IGF-I), body weight, and serum albumin was studied in 17 patients on continuous ambulatory peritoneal dialysis (CAPD) and 17 patients on hemodialysis. Patients were matched for gender, age (33-83 years), body mass index (16.7-36.1 kg/m2), hematocrit, concentrations of serum growth hormone, and duration of dialysis (1-210 months). Serum IGF-I concentration was measured by radioimmunoassay (Incstar) and albumin by a standard laboratory technique. CAPD patients had significantly lower serum albumin concentrations than hemodialysis patients, whereas IGF-I levels in the two groups were similar and did not differ from those in 18 normal subjects. We did not find significant positive correlations between IGF-I and serum albumin levels in CAPD or in hemodialysis patients. On the other hand, IGF-I showed a strong positive correlation with body weight (for the CAPD group r = 0.523; for both groups together r = 0.493). Both groups (CAPD and hemodialysis) and CAPD patients who weighted less than 60 kg (44%) had significantly lower serum IGF-I levels (113.5 +/- 10.2 and 108.8 +/- 15.7 micrograms/l +/- SEM, respectively) than patients who weighed 60-80 kg (38.3%; 181.2 +/- 20.9 and 196.6 +/- 27.2 micrograms/L +/- SEM, respectively) or above 80 kg (17.6%; 205.2 +/- 37.7 and 229.5 +/- 43.5; micrograms/L +/- SEM, respectively). It therefore appears that a low serum IGF-I level is a better indicator of malnutrition in CAPD and hemodialysis patients than low serum albumin.

Adult↗
PubMed1994

Changes in body composition of children with chronic renal failure during growth hormone treatment.

Growth hormone (GH) has different known metabolic effects, among which are lipolysis and anabolic action. We have studied the changes in body composition of children with chronic renal failure (CRF) after 1 year of daily treatment with GH. Body fat percentage and fat body mass (FBM) were derived from four site skinfold measurements; lean body mass (LBM) from total body potassium (TBK) and mid-arm muscle circumference (MAMC); bone mineral density (BMD) was measured by dual photon absorptiometry. GH treatment had a positive effect on weight, height and MAMC, but no effect on LBM (as reflected by TBK), FBM and BMD. Z-scores were derived in order to compare subjects with a normal population. While no significant change in z-score was noticed for weight, height, MAMC, FBM and BMD, TBK decreased during treatment. We conclude that GH therapy does not ultimately increase LBM in CRF patients compared with other GH-treated groups.

Body Composition↗
PubMed1994

Changes in body composition, resting energy expenditure, and thermic effect of food in short children on growth hormone therapy.

The effect of growth hormone (GH) treatment on body composition, resting energy expenditure (REE), and the thermic effect of food (TEF) was studied in 10 prepubertal boys (aged 6.2 to 9.5 years, with subnormal spontaneous GH secretion during the first 6 months of treatment [0.2 IU/kg.dl]). Patients were studied before and at 2, 4, and 6 months after commencing treatment. Height and weight increased significantly during treatment (112.2 +/- 4.5 to 117.2 +/- 6.0 cm and 18.0 +/- 2.8 to 20.8 +/- 3.2 kg, respectively). Body fat percent decreased significantly (15.93% +/- 4.08% to 11.97% +/- 3.30%, P < .0002), but was not different at 4 and 6 months. Total body potassium (TBK) increased significantly (39.15 +/- 5.77 to 48.70 +/- 6.35 g, P < .001) during treatment. When correcting for the expected changes in body composition over time, height and weight were still shown to increase, fat percent decreased significantly, but TBK and mid-arm muscle circumference (MAMC) were not different from the expected values. REE increased significantly during treatment, but when it was expressed per TBK or corrected for the change in kilograms of fat-free body mass (FFBM), it increased only at 2 months and stabilized thereafter. The TEF was increased at 2 and 4 months of treatment and returned to pretreatment levels at 6 months of treatment. Substrate utilization as studied by indirect calorimetry pointed toward a significant protein-sparing effect during the first 4 months of treatment; this change tended to disappear in resting energy metabolism by 6 months of GH treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Composition↗
PubMed1994

Urinary free cortisol values in children under stress.

Children with adrenocortical insufficiency are commonly instructed to increase their baseline glucocorticoid replacement doses by three to five times during periods of stress such as surgery or febrille illness. We conducted this to determine whether these recommendations reflect the actual change in urinary free cortisol (UFC) output during stress. The 24-hour UFC excretion was determined in 78 children who were admitted to a general pediatric department or intensive care unit with temperature > 38.7 degrees C, after major surgery, or during status epilepticus; we reevaluated 43 of the patients 2 weeks after recovery. In addition, the 24-hour UFC levels were determined in 127 healthy children aged 1.8 to 17 years. The UFC level positively correlated with age (r = 0.254; p < 0.001). The amount of UFC per gram of creatinine was inversely correlated with age (r = 0.255; p < 0.001). The amount of UFC per surface area was independent of age. The mean change in the level of UFC per square meter surface area was highest among children who had cardiothoracic surgery and those with multiple trauma. The increase in UFC level during bacterial infection was significantly greater than that during viral infection. The current recommendation to increase the dose to three to five times the baseline glucocorticoid dose during times of stress may underestimate the changes in UFC found in some patients with major surgery, trauma, or certain serious bacterial infections. Production rate studies are needed to prove this point.

Abdomen, Acute↗
PubMed1994

Age as a determinant of the impact of growth hormone therapy on predicted adult height.

OBJECTIVE: Final adult height is determined by both childhood and pubertal growth. The later is a function of growth velocity and bone maturation, and both are regulated by growth hormone. In a study of the safety and efficacy of GH therapy, we analysed the impact of age on bone maturation and predicted adult height. PATIENTS AND METHODS: The subjects were 65 male patients with GH deficiency, as diagnosed by pharmacological or physiological tests, who participated in a multicentre trial and completed 3 years of hGH therapy. The age range at initiation of therapy was 3.1-15.7 years. Subcutaneous injections of hGH were given in a dose of 0.3 mg/kg/week, in thrice-weekly doses. Calculation of the adult height prediction was performed on annual growth parameters using the Bailey-Pinneau, TW-II and Roche methods. RESULTS: The rate of pubertal advancement correlated positively with the child's age at initiation of therapy. The bone age advanced in positive correlation with chronological age, and by the end of 3 years of hGH therapy the delta-bone age/delta-chronological age ratio increased to 1.5 for children with an age at start of therapy of 10.7 years. During the adolescent years, the predicted gained height over 3 years of therapy declined, in correlation with age, and became negative at a therapy-initiation age of 12.9 years. CONCLUSIONS: In a retrospective analysis of a group of children with heterogeneous GH secretory ability, GH induced acceleration of growth, around the age of normal puberty, advanced the age of pubertal onset and accelerated pubertal progression which, in turn, expedited bone maturation and thereby restricted predicted adult height gain from hGH therapy.

Adolescent↗
PubMed1994

Overnight secretion pattern of growth hormone, sex hormone binding globulin, insulin-like growth factor-1 and its binding protein in obese and non-obese women with polycystic ovarian disease.

The pathophysiological mechanism underlying polycystic ovarian disease (PCOD) is different in obese and lean women. In obese patients the basic disorder is insulin resistance and hyperinsulinemia. In non-obese women the dominant derangement is a relative excess of luteinizing hormone (LH) and growth hormone (GH) production. The levels of GH, LH, sex hormone binding globulin (SHBG) and insulin-like growth factor binding protein-1 (IGFBP-1) were significantly lower and insulin levels considerably higher in obese PCOD women as compared to their non-obese counterparts. There was, however, no difference in the mean IGF-1 levels found in these two groups. The present study was designed to investigate whether, in addition to the mean levels, the overnight pattern of GH, IGF-1, IGFBP-1 and SHBG differed in obese women with polycystic ovaries as compared to that observed in the non-obese PCOD patients. Eight women with PCOD diagnosed by clinical, sonographic and hormonal means were studied. Four had basal body mass index exceeding 27. Blood samples were collected every 20 min over a period of 8 h, starting at 23:00 h. Twenty-four samples were collected from each patient and examined in one batch for GH, IGF-1, IGFBP-1, SHBG and insulin. The secretion patterns of the above substances during the late night (23:00-03:00 h) and early morning (03:00-07:00 h) hours were examined and compared in obese and non-obese PCOD women. Neither GH nor IGF-1 showed a distinct overnight secretion pattern. The overnight secretion patterns of IGFBP-1 and SHBG were similar in obese and non-obese women--the former showing a constant rising during the night and the latter exhibiting a converse trend. The integrated insulin levels were much higher during the late night as compared to early morning hours in all patients. It is proposed that the specific secretion pattern of IGFBP-1 is not directly dependent on body fat mass but is regulated by insulin in both obese and non-obese patients.

Adult↗
PubMed1994

Effect of long-term growth hormone therapy on bone age and pubertal maturation in boys with and without classic growth hormone deficiency.

We evaluated the effect of growth hormone (GH) therapy on bone age, pubertal maturation and predicted adult height in two groups of boys treated for 4 years: 40 growth hormone-deficient boys who had growth hormone response to provocative stimulation < 10 micrograms/L (GHD group) and 43 boys whose stimulated growth hormone > or = 10 micrograms/L (group with neurosecretory dysfunction (NSD)). All patients had a subnormal integrated concentration of growth hormone < or = 3.2 micrograms/L, height < -2 SD, growth velocity < 4.5 cm/yr, and bone age < or = -2 SD for chronologic age. Patients were treated with recombinant growth hormone, 0.1 mg/kg per dose given three times a week. The pretreatment height SD of the GHD group (-3.6 +/- 1.0) was less than that of the NSD group (-2.7 +/- 0.7; p < 0.001). After 4 years of therapy, both groups had catch-up growth (GHD group to -2.0 +/- 1.3 height SD (n = 35), and NSD group to -1.4 +/- 0.7 height SD (n = 32)); the rate of height SD gain was better in patients with GHD (p < 0.01). The response to growth hormone was inversely related to pretreatment chronologic age (p < 0.001). The Tanner-Whitehouse II predicted adult height improved for both groups: +9.3 +/- 7.7 cm in the GHD group, giving an adult height SD of -0.9 +/- 1.0, and +5.4 +/- 5.5 cm in patients with NSD, for an adult height SD if -0.8 +/- 0.7. Testosterone levels became higher in the NSD group after 2 years and remained higher at year 4. We conclude that patients respond favorably to growth hormone therapy and in a manner similar to patients with GHD. Initiation of therapy at a younger age gives a greater improvement in gained height and predicted adult height.

Age Determination by Skeleton↗
PubMed1993

Plasma cortisol levels increase with age in obese subjects.

In order to assess the influence of age, sex, and body mass on plasma cortisol concentrations, we measured the 24-hour Integrated Concentration (IC) of cortisol (F) in 36 obese subjects (16 males, 20 females) aged 5.3-56.4 years, BMI = 35.5 +/- 7.3 kg/m2 and compared with 119 nonobese subjects, body mass indices (BMI) 21.2 +/- 2.7 kg/m2, aged 8.8-66.2 years (55 males, 64 females). Subjects were nondiabetic, normotensive, without history of psychiatric illness, and otherwise in good health. IC studies were performed using a continuous blood withdrawal methodology, and IC-F was assayed from the 24 hour pooled sample by a protein binding method. The effect of age and gender on IC-F was analyzed by multivariate regression. In the nonobese group there was no effect of age or sex on IC-cortisol levels, the mean IC-F = 173.8 +/- 44.1 nmol/L. A statistically significant but weak negative effect of BMI on IC-cortisol (r=-.18, p<0.05) was present. In the obese subjects there was a significant increase in IC-cortisol levels with age IC-F(nmol/L) = 2.76 x age(years) + 85.0 (r2=.36, p<0.0001). IC-cortisol levels tended to be lower in obese males than females when controlled for age (p<0.05). We conclude that in nonobese subjects IC-F levels are independent of age and gender. However, there is a significant increase of IC-cortisol levels with age in obese individuals. The observed increase of IC-cortisol with age may contribute to metabolic complications of obesity.

Adolescent↗
PubMed1993

Polycystic ovaries in non-obese and obese patients: possible pathophysiological mechanism based on new interpretation of facts and findings.

This study was designed to investigate the basic concentrations of different hormones in obese and non-obese patients with polycystic ovarian disease (PCOD). Eight women with PCOD, of whom four were obese with body mass index (BMI, kg/m2) of > 25 and four were non-obese with BMI < 25, volunteered to participate in this study. Serum samples were taken every 20 min over an 8 h period, starting at 2300 h, on day 5 of a spontaneous or gestagen-induced cycle. Basic insulin concentration was found to be significantly higher in the obese women compared with their non-obese counterparts (P < 0.0001). Serum concentrations of insulin-like growth factor binding protein (IGFBP-I) and sex hormone binding globulin (SHBG) were found to be significantly lower (P < 0.001 for both hormones) in the obese compared with the non-obese women. Serum concentrations of insulin-like growth factor I (IGF-I) did not differ between the two groups. The non-obese women had significantly higher serum concentrations of luteinizing hormone (LH) (P < 0.001) and of growth hormone (GH) (P < 0.002) than their obese counterparts. Based on these results, two models of the development of PCOD were suggested. In obese women, hyperinsulinaemia causes an excessive production of androgens through the enhancement of IGF-I receptors which, in synergism with LH, causes increased activity of cytochrome P-450c 17a. In non-obese patients, relative increase of GH concentration stimulates excessive ovarian IGF-I production. At this point synergism with LH results in excessive production of androgens by the same mechanism as in obese patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Effect of timing of growth hormone administration on plasma growth-hormone-binding activity, insulin-like growth factor-I and growth in children with a subnormal spontaneous secretion of growth hormone.

Since normal pulsatile growth-hormone (GH) secretion displays a major and consistent surge during sleep, we studied the effect of timing of GH supplementation on plasma GH-binding protein activity (GH-BP), insulin-like growth factor-I (IGF-I) and growth. 34 prepubertal subjects (28 boys, 6 girls) aged 8-11 years, of short stature (< 2 SD for age), with a GH response to provocative test > 10 micrograms/l and a subnormal 24-hour GH secretion (< 3 micrograms/l), were randomly allocated to receive Bio-Tropin (recombinant GH, Bio-Technology, Israel) 0.81 IU/kg/week in 3 equally divided doses. GH was administered either at 8.00-10.00 h (M group), 14.00-16.00 h (AN group) or 19.00-21.00 h (NT group). Height velocity, IGF-I and GH-BP were determined prior to and after 6 and 12 months on GH therapy in the three groups. There was no significant difference between the three groups in the growth response, IGF-I and GH-BP increase, all of which increased significantly during GH therapy. Although GH levels after the injection decline to preinjection levels after 10 h, the changes induced by GH therapy, as reflected in IGF-I and GH-BP, last in the circulation long enough to prevent fluctuations in its action. The similarity of IGF-I and of GH-BP levels in the three treatment groups might explain the similar growth effects of the 3 protocols.

Carrier Proteins↗
PubMed1993

Improved method for predicting adult height of pubertal boys using a mathematical model.

Several methods for adult height prediction are currently in use. All are subject to a wide range of error which is thought to result, at least in part, from the use of bone age estimation. Following the suggestion made by Karlberg to predict adult height of pubertal children by the use of the 'Infancy-Childhood-Puberty model' (ICP), growth data of 39 normal boys who were followed from infancy until adult height was attained were reviewed. Use of the ICP model alone and without bone age resulted in more accurate predictions of adult height than those made by the methods which required bone age determination, the Bayley-Pinneu (BP) and the Tanner-Whitehouse methods (TW). The absolute error of prediction was 3.4 cm as compared to 5.3 (BP) and 4.9 cm (TW) (p < 0.05) and maximal range of error was 10 cm as compared to 22 (BP) and 21 cm (TW) (p < 0.05). Finally, based on the ICP model, a new equation which incorporates paternal height was been derived. This equation, termed ICP-New (ICPN), resulted in even better accuracy: absolute error of prediction was 2.3 cm as compared to 3.4 cm (ICP) and maximal range of error was 6 cm as compared to 10 cm (ICP) (p < 0.05). It is concluded that the ICP model and the ICPN equation may predict the adult height of pubertal boys more accurately than the methods which use bone age.

Adolescent↗