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S L Drop

Publications and source records attributed to S L Drop.

At least 91 records · Page 5Linked to original sources

Effect of growth hormone administration frequency on 24-hour growth hormone profiles and levels of other growth related parameters in girls with Turner's syndrome. Dutch Working Group on Growth Hormone.

OBJECTIVE: The optimal dose and frequency of GH administration in Turner's syndrome is unknown. There is some evidence that a schedule which mimics normal pulsatile GH secretion may be more effective than a single daily dose. We therefore wished to study the influence of the frequency of GH administration on 24-hour GH profiles and levels of other growth-related factors in Turner's syndrome. DESIGN: Four weeks after initiation of 0.05 microgram/kg/day ethinyl oestradiol, we compared twice daily (b.i.d.-fractionated dose) with once daily (o.d.) s.c. injections of 6 IU GH/m2/day in a 2-week cross-over design with a 2-week washout interval. Each treatment period was concluded with 24-hour GH profile tests. Pretreatment plasma/serum levels of GH, IGF-I, binding proteins for GH (GHBP) and IGF-I (IGFBP-3) were used as a basis for comparison of the levels found after each regimen. A one-compartment open model was used for estimation of pharmacokinetic parameters. SUBJECTS: Ten previously untreated girls with Turner's syndrome aged > or = 11 years. MEASUREMENTS: Plasma levels of GHBP by standardized binding assay; GH, IGF-I, and IGFBP-3 serum/plasma levels by radioimmunoassay. RESULTS: There were significantly higher maximum GH levels and a greater area under the curve with o.d. than with b.i.d. GH, while GH clearance was greater with b.i.d. The pharmacokinetic values with o.d. injections were in conformity with values for healthy and GH-deficient children. Pretreatment GHBP levels tended to be high compared with values in healthy prepubertal children. These levels decreased with GH therapy, significantly so with b.i.d. GH only. There was a significant increase in levels of IGF-I and IGFBP-3, irrespective of regimen. The IGF-I to IGFBP-3 ratio, a possible indicator of the growth response, rose significantly and comparably with both regimens. There was no consistent diurnal variation with either regimen in GHBP, IGF-I or IGFBP-3 levels. Four-hourly levels of GH, GHBP, IGF-I and IGFBP-3 were not correlated. CONCLUSIONS: Although the 24-hour profiles differed during once or twice daily administration of the same total growth hormone dose, the diurnal pattern and mean levels of factors involved in the biological effects of GH are comparable for both regimens.

Adolescent↗

Comparison of complete and incomplete suppression of pituitary-gonadal activity in girls with central precocious puberty: influence on growth and predicted final height. The German-Dutch Precocious Puberty Study Group.

The question as to whether treatment with short-acting or with slow-release gonadotropin-releasing hormone (GnRH) agonists has different effects on growth and bone maturation when treating girls with central precocious puberty has not yet been studied. In a meta-analysis, we compared 21 naive girls with central precocious puberty who were treated with buserelin with 22 naive girls with central precocious puberty who received Decapeptyl in depot form. Treatment lasted for at least 18 months. At the start of therapy, chronological age, bone age, growth velocity and pubertal stage in the two groups were very similar. During the first 6 months of treatment, significantly more phases of incomplete suppression of pituitary-gonadal activity occurred in the buserelin group. As a result, growth velocity and bone maturation (delta bone age/delta chronological age) remained significantly higher than in the Decapeptyl Depot group (p < 0.0001 and p < 0.01, respectively). In contrast to the Decapeptyl Depot group, the height standard deviation score (SDS) for bone age in the buserelin group did not change significantly in the first 6 months of treatment, and the predicted adult height decreased. Between the 6th and 18th months of therapy, the development of growth rate, delta bone age/delta chronological age, height SDS for bone age and predicted adult height in both groups became almost identical. However, the rate of growth and bone maturation in the buserelin group remained faster than in the Decapeptyl group, though not significantly so. The mean predicted adult height had risen significantly after 18 months in the Decapeptyl Depot group but not in the group treated with buserelin.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗

Long-term effects of treatment for acute lymphoblastic leukemia with and without cranial irradiation on growth and puberty: a comparative study.

We investigated the comparative effect on long-term growth of CNS prophylactic treatment for acute lymphoblastic leukemia (ALL) with either 25-Gy cranial irradiation or moderate-dose i.v. methotrexate. In 80 children with complete continuous first remission, data on growth and pubertal development were investigated up to 11 y from ALL diagnosis. Forty patients had 25-Gy cranial irradiation, 16 of them with high-risk factors and 24 without. Another 40 non-high-risk ALL patients had moderate-dose methotrexate. Chemotherapy lasted 3 1/4 y for high-risk ALL patients and 2 1/4 y for those not at high risk. Pubertal development and final height were assessed separately for girls diagnosed before or after age 7 and for boys before or after age 9. All patients had a similar decline in height SD score during the first 6 mo of treatment, which persisted in irradiated children only. The nonirradiated group had no further decline. Catch-up growth only started when chemotherapy ended for irradiated and non-irradiated patients alike. Five y after cessation of treatment, changes in height SD score for nonirradiated children remained within the range for healthy children against a significant decline in height SD scores for irradiated children. Pubertal development in irradiated girls diagnosed before age 7 was within normal range, but their final height was disappointing due to a blunted growth spurt. In contrast, irradiated girls diagnosed later had a delayed onset of puberty but satisfactory final height. Comparable results were found in boys.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Gene expression of the six insulin-like growth factor binding proteins in the mouse conceptus during mid- and late gestation.

The insulin-like growth factor-binding proteins (IGFBPs) comprise at least six distinct species that may modulate the action of IGFs. IGFs are important regulators of fetal growth and differentiation. To define sites of IGFBP mRNA synthesis, we have used in situ hybridization techniques in mouse conceptuses of different gestational ages (11-18 days). Expression of mouse (m) IGFBP-1 was detected in mouse conceptuses after day 12 of gestation and was restricted to the liver. Transcripts for mIGFBP-2, -4, and -5 were detected in various tissues and were found in all stages tested. In contrast, expression of mIGFBP-3 and -6 could be only weakly detected in late gestational conceptuses. Comparison of the expression patterns of mIGFBP-2, -4, and -5, which were found widely distributed in mouse conceptuses, revealed that mIGFBP-2 was expressed in the mesoderm-derived part of the tongue (day 13.5), but mainly in the ectodermal layer. Transcripts for mIGFBP-4, however, were detected only in the mesodermal part, whereas expression of mIGFBP-5 was restricted to the ectodermal layer. A similar distribution pattern was observed in the lung (day 18). In general, expression of mIGFBP-2 and -5 was detected in the same cells, whereas mIGFBP-4 and -5 were expressed mainly in different cell types. These data suggest that the different mIGFBPs might play distinct roles in mouse embryonal and fetal life.

Animals↗

Levels of growth hormone, insulin-like growth factor-I (IGF-I) and -II, IGF-binding protein-1 and -3, and cortisol in prednisone-treated children with growth retardation after renal transplantation.

Growth retardation after renal transplantation (RTx) is generally attributed to prednisone (PDN) administration, although the exact mechanism is poorly understood. In a group of 19 growth-retarded post-RTx children, we studied the effect of alternate day (AD; n = 12) and daily (D; n = 7) PDN therapy (0.10-0.25 mg/kg.day) on 24-h plasma GH and cortisol profiles, once in group D and twice on successive days in group AD. The maximal plasma GH response to arginine provocation (ATT) and plasma levels of insulin-like growth factor-I (IGF-I), IGF-II, and serum IGF-binding proteins (IGFBP) were also determined. The pulsatile character of the 24-h GH secretion was sustained in all patients. However, mean GH levels were significantly lower as compared with published data for healthy children, corrected for pubertal stage and sex. The highest mean GH levels were found in boys and girls in late puberty. Group AD had similar 24-h GH profiles whether on or off PDN treatment, which did not differ significantly from the GH profiles observed in group D. The maximal GH response during ATT was greater than 10 micrograms/L in 57% of the children. Group D had significantly lower mean and maximal cortisol levels than group AD, but all patients had a normal diurnal variation. Plasma immunoreactive IGF-I and IGF-II, and serum IGFBP-1 levels were normal, but serum levels of IGFBP-3 were increased. A significant negative correlation was found between the glomerular filtration rate and serum IGFBP-3 levels. In conclusion, our findings indicate that growth-retarded renal allograft patients, receiving either alternate day or daily PDN therapy, have decreased GH secretion, but a normal diurnal rhythm of GH and cortisol secretion as well as normal plasma IGF-I and -II levels. However, growth retardation after RTx may not solely be the result of decreased GH secretion. Renal graft impairment together with decreased IGF bioavailability may, in addition to the presumed direct effects of PDN on cartilage, contribute to the growth retardation after RTx.

Adolescent↗

Localization of the epitope of a monoclonal antibody against human insulin-like growth factor binding protein-1, functionally interfering with insulin-like growth factor binding.

In order to identify regions in insulin-like growth factor binding protein-1 involved in the binding of IGFs, we tested three monoclonal antibodies, designated MAb A, B, and C on their interference with IGF-binding. Monoclonal A interfered with the binding of IGF to IGFBP-1 as determined by immunoprecipitation whereas monoclonal B and C did not. Furthermore MAb A was found to abolish IGFBP-1 inhibition of IGF stimulation in an in vitro proliferation assay. The epitopes of all three monoclonal antibodies were found to be located within the C-terminal part of IGFBP-1. The regions surrounding residue 188-196 and 222-227 are especially important for antibody recognition. These results indicate that MAb A functionally interferes with the binding of IGF to IGFBP-1. Furthermore, we suggest that part of the epitope of MAb A is located at or sterically near the IGF binding domain of IGFBP-1.

Amino Acid Sequence↗

[Comparison between complete and incomplete suppression of the hypophyseal-gonadal axis in girls with central precocious puberty: effect on growth and prospective final height].

BACKGROUND: Whether short-acting or slow-release gonadotropin-releasing hormone agonists have different effects on growth and bone maturation in children with central precocious puberty is still unknown. METHODS: In a meta-analysis, we studied 21 previously untreated girls with central precocious puberty treated with Buserelin and 22 previously untreated girls with central precocious puberty treated with Decapeptyl Depot. Duration of treatment was at least 18 months in both groups. RESULTS: At start of therapy, chronological age, bone age, height velocity and pubertal stage were well comparable between the groups. During the first 6 months of treatment, clinical and biochemical escapes from suppression were more frequent in the Buserelin group; height velocity and bone maturation (delta bone age/delta chronological age) remained significantly higher (p < 0.0001 and p < 0.01, resp.) in Buserelin than in Decapeptyl Depot patients. In contrast to the Decapeptyl Depot group, in the Buserelin patients height standard deviation score for bone age did not change and predicted adult height decreased. From 6 to 18 months of therapy, the development of height velocity, delta bone age/delta chronological age, standard deviation score for bone age and predicted adult height showed an almost parallel course in both groups. Height velocity and bone maturation tended to be faster in the Buserelin group. Mean predicted adult height rose significantly in the Decapeptyl Depot group, but not in the Buserelin-treated girls. CONCLUSIONS: A slow-release gonadotropin-releasing hormone agonist appears to be superior to short-acting drugs not only in terms of long-term tolerance but also for achieving the auxological objectives in central precocious puberty therapy. This is mainly due to their faster and more complete suppression of gonadotropins during the first 6 months of treatment.

Age Determination by Skeleton↗

Growth, bone maturation and height prediction after three years of therapy with the slow release GnRH-agonist Decapeptyl-Depot in children with central precocious puberty.

More than 100 patients with central precocious puberty are participating in this international multicenter study using monthly i.m. injections of the slow-release GnRH agonist Decapeptyl-Depot. In 15 patients, Decapeptyl-Depot treatment could be discontinued after 2 years of therapy. Gonadal suppression was promptly reversible in all of them, as shown by prepubertal low gonadotrophin- and sex steroid levels. Of the remaining 90 patients, 40 have been treated for more than 3 years, including 33 girls and 7 boys. Plasma levels of LH, FSH, estradiol and testosterone dropped to the prepubertal range after one month of Decapeptyl-Depot and remained there for the whole period of therapy. At start of therapy, mean chronologic age of these 40 children was 6.6 +/- 1.4 (SD) years, mean bone age 10.2 +/- 1.9 years. Mean predicted adult height increased in the boys from 173.6 +/- 13.8 (SD) cm at start of therapy to 184.6 +/- 17.0 cm after 3 years. Predicted adult height increased in girls from 158.0 +/- 12.2 to 161.0 +/- 7.5 cm. Undue side effects were not seen, long term tolerance was good. It is concluded that Decapeptyl-Depot injected i.m. every 4 weeks suppresses the pituitary-gonadal axis in children with central precocious puberty without clinical or biochemical escapes, and leads to an increase in predicted adult height by more than 3 cm in all boys and in 53% of the girls after three years of treatment.

Adolescent↗

Evaluation of young women with congenital adrenal hyperplasia: a pilot study.

To evaluate the outcome of medical and surgical treatment of 10 young women with congenital adrenal hyperplasia (CAH), final height, weight, body proportions and body hair growth as well as aspect and functionality of the external genitalia were assessed. The final height was below-2 SD of the target height in 55%, though the body proportions were in the normal range. Only 3 patients were menstruating regularly. Scores for 'hormonal' body hair growth were in a higher range. Gynaecological examination revealed that in 5 out of 9 patients, the genitalia were functionally acceptable. This pilot study stresses that from birth into adulthood of female patients with CAH there is a need for a combined therapeutic approach by a paediatric endocrinologist, a surgeon and a psychologist. This will improve the physical and psychosocial well-being of these patients.

Adolescent↗

Dose-response study of biosynthetic human growth hormone (GH) in GH-deficient children: effects on auxological and biochemical parameters. Dutch Growth Hormone Working Group.

A multicenter dose-response study evaluated the effect of two different doses of biosynthetic GH on auxological and biochemical parameters in 38 prepubertal children with GH deficiency (GHD). Twenty-one were newly diagnosed, while 17 transfer patients had been on GH treatment for at least 1 yr before the study. New and transfer patients alike were treated with either 2 or 4 IU GH/m2.day sc. At evaluation all new patients had completed 1 yr of treatment, while transfers had completed 2 yr of treatment under study. In the new patients both doses resulted in a significant increase in height velocity (HV) and height SD score (SDS), with comparable bone maturation. After correction for the severity of GHD, the increase in HV SDS was significantly greater with 4 IU than with 2 IU (P less than 0.01). In the transfer patients HV, height SDS, and predicted adult height only increased significantly with 4 IU (P less than 0.05). Bone maturation was comparable for the two doses. There was a significant correlation between first year growth response and GH dose. In the new patients, the plasma insulin-like growth factor-I (IGF-I) concentration increased significantly without a significant difference between dosage groups. There was a positive correlation between growth response and increment of plasma IGF-I SDS. In new and transfer patients alike, above normal plasma IGF-I levels were observed, particularly with 4 IU. Hemoglobin-A1 remained constant with both GH doses in both groups, while cholesterol and LDL levels tended to decrease. In the new patients, the mean apolipoprotein-A1 level was lower than the control value after 1 yr on 4 IU GH. Treatment with 4 IU GH/m2.day led to a greater growth response than a dose of 2 IU in newly diagnosed as well as previously treated GHD patients. Bone maturation was comparable for both doses. No adverse effects were observed with the higher GH dose, but the long term effects on IGF-I and lipid metabolism need further attention.

Adolescent↗

Structural aspects of the IGFBP family.

To date six IGF binding proteins (IGFBP) have been characterized. Analysis of the amino acid sequence reveals that the IGFBPs are clearly distinct but are sharing regions with strong homology. Specifically the hydrophobic cysteine rich N-terminal region and to a lesser extend the C-terminal part are preserved. The alignment of the cysteine molecules is strongly conserved across the 6 IGFBPs. The middle one-third region, where no cysteines are present (except for IGFBP-4) is most divergent. IGFBP-3 and -4 are glycosylated, whereas IGFBP-1 and -2 contain an Arg-Gly-Asp sequence near the carboxyl terminus. Determination of the number of free-SH groups of IGFBP-1 and -3 has revealed that most likely all cysteine residues are involved in disulfide bond formation. All members of the IGFBP family bind IGF-I and IGF-II with about equal affinity. Studies involving deletion mutation and site-directed mutagenesis of IGFBP-1 and -3 have suggested that the three-dimensional structure of the protein plays an important role in IGF binding. However at present it is unclear whether the IGFBPs share one or more specific IGF binding domain. The predominant function of the IGFBPs is to allocate IGF in the various body fluid compartments and tissues and to modulate IGF binding to receptors. For this purpose there exists a very sophisticated control of the routing of circulating IGF both from and to the cell. There is mounting evidence that the structure of the IGFBP proteins plays a key role in the regulation of IGF bioavailability, by modulating its molecular size, capillary membrane permeability, target tissue specificity, cell membrane adherence and IGF affinity.

Amino Acid Sequence↗

Site-directed mutagenesis of the N-terminal region of IGF binding protein 1; analysis of IGF binding capability.

To define domains involved in IGF binding 60 N-terminal amino acid residues of IGFBP-1 were deleted. This deletion resulted in loss of IGF binding suggesting that the N-terminus may enclose an IGF binding domain. However, most point mutations introduced in this region did not affect IGF binding. In contrast to Cys-34, only substitution of Cys-38 for a tyrosine residue abolished IGF binding. With the determination that all 18 cysteine residues are involved in disulphide bond formation our data suggest that, although not all cysteines contribute to the same extent, the ligand binding site may be spatially organized.

Amino Acid Sequence↗

Long-term results with a slow-release gonadotrophin-releasing hormone agonist in central precocious puberty. Dutch-German Precocious Puberty Study Group.

As part of an ongoing international multicentre study, 19 children (14 girls, 5 boys) with central precocious puberty (CPP) were treated with a slow-release gonadotrophin-releasing hormone (GnRH) agonist, triptorelin, for 4 years. After 3 years of treatment, height velocity stabilized at 4.0 cm/year. Predicted adult height (mean +/- SD) increased from 158.9 +/- 6.8 to 164.9 +/- 6.6 cm in girls (n = 14, p less than 0.01), and from 174.4 +/- 18.5 to 184.3 +/- 17.1 cm in boys (n = 4, p less than 0.05). In 12 additional girls who had started the multicentre study but discontinued triptorelin treatment after 2.2 +/- 0.5 years, menses started 9.8 +/- 3.7 months after cessation of treatment in all but one patient. Height velocity increased over the first 6 months after discontinuation of treatment, from 3.6 +/- 0.1 to 5.4 +/- 2.5 cm/year, and remained higher than pretreatment values in the second 6 months, but decreased subsequently. Bone maturation increased, and no significant improvement in predicted adult height was observed. For auxological reasons, therefore, it may be advisable to continue triptorelin treatment for as long as possible. Concomitant growth hormone (GH) therapy was initiated in three girls with CPP with height velocities of 3.2-3.6 cm/year after 3 years of treatment with triptorelin and predicted adult heights of less than the third centile for Dutch girls. Prior to the administration of GH, all patients had subnormal 24-hour GH profiles and GH responses to arginine provocation. GH treatment increased height velocity markedly in all girls, and improved predicted adult height.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗

Growth and pubertal development during and after treatment with a slow-release gonadotropin-releasing hormone agonist in central precocious puberty.

The auxological data of 25 patients (21 girls, 4 boys) with central precocious puberty (CPP), treated for 4 years with a slow-release gonadotropin-releasing hormone agonist [Decapeptyl-controlled release (D-CR) 3.75] every 4 weeks intramuscularly, and of 6 patients (3 girls, 3 boys), treated for 5 years, are presented. After 3 years of D-CR a stabilization of height velocity (HV) at about 4 cm/year was observed. Bone maturation (ratio of change in bone age to change in chronological age; delta BA/delta CA) slowed down to a mean delta BA/delta CA ratio of 0.5 +/- 0.2 (mean +/- SD) measured over 48 months. As a result, predicted adult height (PAH) improved from 156.3 +/- 7.4 to 162.2 +/- 6.8 cm in girls (p less than 0.001) and from 174.4 +/- 18.6 to 184.3 +/- 17.1 cm in boys after 4 years. In the 5th year an ongoing improvement of PAH was observed. 20 additional girls discontinued D-CR for at least 12 months after treatment with D-CR for 2 years or more. In 11 girls menses started after 10.6 +/- 3.1 months; 9 girls had no menarche after 12-16 months. HV increased in the first and second 6 months to a level of about 6.0 cm/year, decreased in the third 6 months after cessation to the level before discontinuing D-CR and decreased further afterwards. Bone maturation (delta BA/delta CA) increased progressively in the first 18 months after discontinuation, with a stabilization at about 1.3. PAH did not change in the first 12 months after discontinuation of D-CR, but showed a decrease afterwards.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗

Mutations in the C-terminal part of insulin-like growth factor (IGF)-binding protein-1 result in dimer formation and loss of IGF binding capacity.

In an attempt to define domains in insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) that are involved in IGF binding, we subjected the carboxyl end of the coding region of IGFBP-1 cDNA to mutagenesis. Mutant cDNAs were isolated, characterized by sequencing, and cloned in an expression vector under control of the simian virus-40 (SV40) early promoter. The constructs were transfected into COS-1 cells, and the mutant proteins, secreted into the culture medium, were analyzed for IGF binding by ligand blotting. The results obtained show that deletion of the C-terminal 20 amino acids or introduction of frame-shifts in this region resulted in loss of IGF binding and for some mutants in the formation of dimeric IGFBP-1 molecules. These dimers are probably formed when cysteine-226 (Cys-226) is missing, and its putative partner is able to form intermolecular disulfide bonds. Site-directed mutagenesis demonstrated that most of the introduced point mutations in the C-terminal region did not affect IGF binding. Only mutation of Cys-226 to tyrosine completely abolished IGF binding, as did the introduction of a negatively charged amino acid in the vicinity of this residue. Again, dimers were observed, supporting that Cys-226 is essential for the conformation of IGFBP-1. In addition, our data suggest that an IGF-binding domain may be located in the vicinity of the intramolecular disulfide bond formed by Cys-226 and its putative partner.

Amino Acid Sequence↗

Treatment of children with central precocious puberty by a slow-release gonadotropin-releasing hormone agonist.

A total of 82 patients (74 girls, 8 boys) are presently participating in an international multicentre trial for treatment of central precocious puberty (CPP) with a slow release gonadotropin-releasing hormone (GnRH) agonist depot preparation: Decapeptyl-Depot (DD). Of these patients, 53 (3 boys) were previously untreated (group 1) and 29 (5 boys) have been treated before with either a short-acting GnRH analogue or cyproterone acetate (group 2). Fifty-one patients (44 girls, 7 boys) were treated with DD for 12 months or more. Basal plasma luteinizing hormone (LH) levels decreased in both groups after 1 year of therapy. The LH response to intravenous GnRH was reduced in both groups. Basal plasma follicle stimulating hormone (FSH) levels decreased in both groups. Stimulated FSH levels were reduced in both groups after 1 year of DD treatment. Plasma oestradiol levels in the girls decreased to prepubertal levels in both groups. In all patients the clinical signs of precocious gonadarche such as breast development and menstruations (girls) and an increased testis volume (boys), did not further progress and sometimes regressed in several patients. Growth velocity decreased in the girls of group 1 from 9.0 +/- 0.72 cm/year (mean +/- SEM) in the last half-year before treatment to 6.3 +/- 0.50 in the first half-year of treatment (P less than 0.01) and to 4.5 +/- 0.23 cm/year in the second half-year (P less than 0.01). After 12 months a stabilization of growth velocity was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗

Growth analysis up to final height and psychosocial adjustment of treated and untreated patients with precocious puberty.

Thirty-four patients (27 girls and 7 boys) with precocious puberty who had reached final height were examined in order to analyze their growth. Thirty patients were diagnosed as having idiopathic precocious puberty, while 4 patients had cerebral organic disorders. Twenty-two patients were treated with cyproterone acetate, 3 with medroxyprogesterone acetate, and 9 patients remained untreated. Growth data of these three groups showed no differences, and final height was not affected by treatment. In patients with precocious puberty, adult height was significantly more often in the lower percentiles (less than or equal to P25, corresponding to an SDS of -0.67) than expected. In both treated and untreated patients, any negative influence of the early onset of puberty on well-being in later life could not be established.

Adaptation, Psychological↗