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Biomedical subjects

Z Laron

Publications and source records attributed to Z Laron.

At least 433 records · Page 24Linked to original sources
PubMedDate not supplied

Intellectual and psychosocial functions of children, adolescents and young adults before and after operation for craniopharyngioma.

An evaluation of intellectual, personal and social functioning was made in 16 young patients with craniopharyngioma. No changes were found in the overall IQ verbal and performances scores before and after operation, however, discrepancies between verbal and performance scores suggest that one of the manifestations of craniopharyngioma in children are disturbance in cognitive functions. The decrease in the quality of life of the patients and their families manifested through the deterioration of familial and social relationships and the decrease in scholastic achievements lead to the conclusion that children with craniopharyngioma and their families require close psychological supervision and counselling both before and after surgery.

Adolescent↗
PubMedDate not supplied

Prolactin secretion in adolescent boys with hypogonadism.

Basal and TRH stimulated plasma prolactin levels were determined in 24 pubertal boys with hypogonadism (Primary: n = 10; secondary: n = 4; tertiary (hypothalamic): n = 10) and controls matched for pubertal stage (n = 12). The differentiation between secondary and tertiary hypogonadism was made with the help of a prolonged LRH test. The TRH test was performed by injecting 200 mcg i.v. in one bolus and taking plasma samples at 0, 15, 30, 60 and 90 minutes. No statistically significant differences were found between any of the groups. It is concluded that determination of basal or TRH stimulated prolactin does not contribute to clarify the etiology of hypogonadism or to determine the grade of damage or dysfunction in the hypogonadic testes.

Adolescent↗
PubMedDate not supplied

A case of Laron syndrome diagnosed in Slovenia.

We report the first case of Laron syndrome (LS) diagnosed in Slovenia. The boy, a product of non-consanguineous Slovenian parents of normal height, presented with slow growth and motor development since birth. At age 4 and 6 years, he had all the characteristic signs of LS, identical to those in growth hormone deficiency (GHD). Laboratory tests showed hypoglycemia, markedly elevated plasma hGH, low serum insulin-like growth factor-1 (IGF-1) with no rise after exogenous hGH, and low serum growth hormone binding protein (GHBP). A sister of the maternal grandfather is short (145 cm) and was found to have below normal serum GHBP, findings compatible with heterozygocity for this disorder.

Child↗
PubMedDate not supplied

Short term effect of intranasal administration of hexarelin--a synthetic growth hormone-releasing peptide. Preliminary communication.

Twice or three times daily intranasal administration of the hexapeptide hexarelin for 7 days to children with short stature and normal growth hormone (GH) secretion evoked a significant rise in serum levels of insulin-like growth factor-1 (IGF-1) and alkaline phosphatase. There was also a significant, within normal limits, rise of thyroid stimulating hormone (TSH) without evidence of thyroxine suppression.

Administration, Intranasal↗
PubMedDate not supplied

Three year IGF-I treatment of children with Laron syndrome.

Nine prepubertal children with Laron syndrome (6 males, 3 females) aged 0.5 to 14.6 years were treated by daily subcutaneous injections of IGF-I in doses of 150-200 micrograms/kg. All patients completed at least one year of treatment; six completed two years and five three years. During the first year, a significant increase in linear growth velocity, from a mean +/- SD of 4.7 +/- 1.3 to 8.2 +/- 0.8 cm/yr (p < 0.0001), was registered. In the second year the growth velocity was lower, but still significantly higher than before treatment. Bone maturation advanced proportionally with chronological age. A reduction in subcutaneous fat tissue was observed despite the body weight increase. There was no aggravation of the characteristic hypoglycemic episodes; on the contrary, there was a better tolerance to fasting. Significant increases in serum alkaline phosphatase, phosphorus and procollagens were registered throughout the study. In conclusion, IGF-I provides an effective replacement treatment for IGF-I-deficient children, mimicking most effects ascribed to growth hormone.

Adolescent↗
PubMedDate not supplied

Growth hormone treatment increases circulating lipoprotein(a) in children with chronic renal failure.

Cardiovascular disease is the major cause of death in chronic renal failure (CRF) patients managed by dialysis or kidney transplantation. Whilst the use of human growth hormone (hGH) is of established benefit in CRF children particularly in those with short stature, in the present study we assessed in CRF children the effect of hGH treatment on circulating lipoprotein(a) [Lp(a)], a genetically determined cardiovascular risk factor. We studied 15 CRF children treated by dialysis or conventional therapy and after kidney transplantation. Overnight fasting blood samples were collected immediately before and after 6 months hGH treatment. In all but one of the children there was a significant increase in serum Lp(a) over the 6 month treatment period -(+)66.7% over the basal levels (range 14 to 180%). After the hGH treatment, in six children Lp(a) levels were elevated to above 300 mg/l, the cut-off level for increased coronary artery disease (CAD) risk. Concomitantly/children also had an increase in serum levels of IGF-I (+96.4%) and insulin (+85.8%). All children had an accelerated growth velocity during the treatment; there was no effect on serum creatinine. Our study shows that hGH treatment in CRF children, though beneficial in its growth promoting effects, increases the already characteristically high levels of serum Lp(a), a risk factor for CAD, and that serum Lp(a) monitoring during treatment with hGH may be useful in evaluating future cardiovascular risk.

Adolescent↗
PubMedDate not supplied

Two types of growth hormone rhythm in boys with constitutional short stature.

The relationship between temporal and quantitative changes in pulsatile growth hormone (GH) secretion and growth of constitutionally short children (CSS) was studied in 19 prepubertal boys and 4 with early adrenarche aged 7.8 to 14 years. Continuous plasma GH monitoring was performed at 30 minutes intervals during 24 hours. The data were analysed by single and serial best fit (BFT) cosinor analysis for rhythm parameters and the Pulsar peak detection program for determining pulsatile properties. The pulsatile patterns were expressed in mean GH concentration, area under the curve, mean pulse area and maximal pulse height but not in the number of pulses. Thirteen out of 23 patterns exhibited significant 24-h compatible rhythms. The studied cohort was divided into two groups, those who exhibited the 24-h circadian rhythm (CIR) and those who lacked it (NCIR). Ultradian 2.5-4 h rhythms were observed in all patients. The NCIR children were significantly shorter than the CIR group (p = 0.017). The CIR boys secreted a significantly higher (p = 0.01) amount of GH during the 24-h span, most of which was during sleep. Our data indicate that the magnitude of pulses rather than their number is responsible for the quantitative differences observed between the two groups of boys with CSS. It is suggested that a lack of 24-h rhythmicity and the associated reduced nocturnal pulsatility play a role in the manifestation of short stature.

Activity Cycles↗
PubMedDate not supplied

Growth during and 2 years after stopping GH treatment in prepubertal children with idiopathic short stature.

Forty-six prepubertal children with idiopathic short stature (ISS), 39 boys and 7 girls, with a mean age of 7.4 +/- 1.8 (SD) years, and mean bone age of 4.5 +/- 1.5 years were treated by human growth hormone (GH) 0.1 U/kg/day s.c. for 30.5 +/- 16.2 months (M +/- SD) (2-5 years range) and were followed for 1-2 years after stopping GH. The mean net gain in height at the end of treatment was 1.03 +/- 0.6 SDS and the bone age SDS was accelerated by 0.95 +/- 1.05. Despite a transitory "catch-down" in growth velocity after stopping GH administration, there was a mean height gain at the end of 2 years follow-up of 0.87 SDS. Children who started treatment before age 6.5 benefited more than older ones. In conclusion, the gain in height observed in children with ISS by GH treatment was maintained during 2 years of follow-up after interruption of treatment. Even if this benefit is transitory and not permanent, it may help short children to achieve self-confidence and raise their physical performance at the critical period of school entry.

Age Determination by Skeleton↗
PubMedDate not supplied

Intronic mutation in the growth hormone (GH) receptor gene from a girl with Laron syndrome and extremely high serum GH binding protein: extended phenotypic study in a very large pedigree.

Laron syndrome (LS) is a hereditary form of GH resistance due to molecular defects in the GH receptor (GHR). Most of the identified mutations are located in the extracellular domain of the receptor, resulting in a lack of serum GHBP in the majority of LS patients. We present an LS patient with supranormal levels of serum GHBP, in addition to 35 of her relatives. The proband is a 3.5 year-old Druse girl with severe short stature (height SDS -5.1), high GH (250 micrograms/l), low IGF-I (2.7 nmol/l) and IGFBP-3 (410 micrograms/l), both unresponsive to exogenous GH. The binding capacity of the serum GHBP was 22 nM (adult reference serum, 0.7 nM), with an affinity constant Ka = 1.9 x 10(9) M-1 comparable to that of normal sera (Ka = 1.7-2.1 x 10(9) M-1). The apparent MW of the GHBP was approximately 60-80 kDa, similar to that of control sera. In the proband's sister, parents, grandparents and uncles, extremely high GHBP values were observed (43.0 +/- 4.8 RSB, n = 10) compared with normal adults (0.81 +/- 0.06 RSB) (p << 0.001). The remaining subjects had normal or moderately elevated GHBP levels. Serum GH in adults with high GHBP was significantly elevated above control values (6.0 +/- 0.9 micrograms/l vs 0.76 +/- 0.13 microgram/l, p < 0.001). Serum IGF-I and IGFBP-3 levels were normal in all the subjects, with the exception of an aunt (IGF-I 3.9 nmol/l) and the proband's sister (IGFBP-3 460 micrograms/l). All the subjects' heights were within the normal range. Analysis of the GHR gene performed in the proband revealed an as yet undescribed homozygous intronic point mutation. It consists of a G-->T substitution at nucleotide 785-1 preceding exon 8, a sequence that encodes the transmembrane domain. This mutation, which destroys the invariant dinucleotide of the splice acceptor site, is expected to alter GHR mRNA splicing and to be responsible for skipping exon 8. The resulting truncated protein that retains GH binding activity is probably no longer anchored in the cell membrane, affecting signal transmission in the homozygous patient and causing high GHBP levels in the heterozygous relatives.

Adolescent↗
PubMedDate not supplied

Serum leptin in obese patients with Laron syndrome before and during IGF-I treatment.

Fifteen patients with primary GH resistance (Laron syndrome, LS) were studied before and during 6 months of daily replacement treatment with IGF-I. The main findings were that patients with LS and normal or high serum GH binding protein (GHBP) were less obese than those with a negative GHBP, and that serum leptin levels varied with body mass as in other types of obesity.

Adult↗
PubMedDate not supplied

Serum insulin-like growth factor-I (IGF-I) levels during long-term IGF-I treatment of children and adults with primary GH resistance (Laron syndrome).

Serum IGF-I levels were measured in 14 patients (9 children and 5 adults) with Laron syndrome (LS) during long-term treatment by IGF-I. Recombinant IGF-I (FK-780, Fujisawa Pharmaceutical Co. Ltd., Japan) was administered once daily subcutaneously before breakfast for 3-5 years to the children and for 9 months to the adults. The initial daily dose was 150 micrograms/kg for children and 120 micrograms/kg for adults. Before initiation of treatment the mean overnight fasting levels of serum IGF-I in the children was 3.2 +/- 0.8 nmol/l (mean +/- SEM), rising to 10 +/- 1.7 nmol/l during long-term treatment even on a dose of 120 micrograms/kg/day. The serum IGF-I levels 4 hours after injection rose from 31.2 +/- 3.5 to 48 +/- 2 nmol/l. In the adult patients, the initial basal IGF-I was 4.1 +/- 0.7 nmol/l, rising to 16.1 +/- 3.84 nmol/l after 8-9 months treatment. Serum IGF-I levels at 4 hours after injection rose in the adult patients from 24.1 +/- 5.8 up to 66.8 +/- 15.4 nmol/l. A progressively increasing half-life during long term exogenous administration of IGF-I to patients with Laron syndrome was demonstrated by following serum IGF-I dynamics after injection. Based on the fact that no antibodies to IGF-I were detected and on findings in previous studies, it is speculated that the increasing serum IGF-I levels during long-term IGF-I treatment are caused by an increase in serum IGFBP-3 induced by chronic IGF-I administration. It is concluded that treatment with IGF-I necessitates regular monitoring of serum IGF-I levels; in patients in whom the age adjusted maximal levels are exceeded, a reduction of the daily IGF-I dose is indicated to avoid undesirable effects.

Adolescent↗
PubMedDate not supplied

Month of birth and subsequent development of type I diabetes (IDDM).

The aim of this study was to find out whether there is a seasonal pattern in the month of birth of children with IDDM in Israel and whether this pattern, if present, differs from that of total live births. One thousand and ninety-five out of 1,188 children and adolescents (0-17 years) who developed IDDM in Israel between 1980-1993 and whose month of birth was known were included in the study. Separate analysis was made for Jews (n = 987) who have a high incidence (10-18/105) and Arabs (n = 108) with a low incidence (2.9/105) of IDDM. The pattern of total live birth distribution in Israel over a 20-year period served as control. A significantly different seasonal pattern was found in the two IDDM populations. Whereas the Jews had the lowest number of births in winter (January-March) and the highest in spring (April-June), the Arabs presented an inverse pattern in the first months of the year. The distribution of births of the children who developed IDDM was different from that observed in total live births in the Jewish population. The findings in the Jewish population in Israel (a high incidence group) support the hypothesis that IDDM is triggered in some children by viral infections transmitted by the mother during pregnancy or in the early postnatal period. In the Arab population (a low incidence group) a protective (immune and/or genetic) mechanism may exist.

Adolescent↗
PubMedDate not supplied

Seasonality of birth in children (0-14 years) with diabetes mellitus type 1 in Baden-Wuerttemberg, Germany.

The aim of the study was to find out whether children with diabetes type 1 in Baden-Wuerttemberg present a pattern of seasonality in their month of birth. A cohort of 1,184 children and adolescents (0-14 years) diagnosed as having diabetes between January 1st, 1987 and June 30th, 1997 were included in the study. Monthly and seasonal patterns of birth of patients with diabetes were compared with the pattern of normal live births (n = 2,724,746) during the years 1972-1997 and the seasonality of onset of disease. Statistical analysis was made using Student's t-test to compare the means between four yearly seasons and single cosinor analysis for a period of 12 months. The children and adolescents with diabetes had a significantly different seasonality in month of birth pattern from that registered in the general population, demonstrating fewer births during the months April-June and July-September. This seasonality pattern also differs from those registered in Israel, Sardinia and Slovenia, in which the population with diabetes type 1 had most births during these months.

Adolescent↗
PubMedDate not supplied

Clinical use of somatomedin-1: yes or no?

Insulin-like growth factor-I (IGF-I) is a polypeptide of 70 amino acids. The circulatory form of IGF-I is synthesised in the liver. The metabolic activity of IGF-I is regulated by 6 IGF binding proteins. the most important being IGF binding protein-3. IGF-I acts via its own receptor, which resembles that of insulin. It has been demonstrated that the effects of pituitary growth hormone (GH, somatropin) on protein metabolism, including growth and effects on nervous and renal tissue, are mediated by IGF-I, whereas these 2 hormones are antagonistic in their effects on insulin and some aspects of lipid metabolism. The biosynthesis of recombinant human IGF-I (somatomedin-1) in 1986 enabled the initiation of clinical trials. The most important involves replacement therapy in primary IGF-I deficiency, such as Laron syndrome (primary GH resistance or insensitivity), and in patients who have developed antibodies to human GH. In Laron syndrome, which is characterised by dwarfism, somatomedin-1 stimulates growth and increases muscle and bone mass, as well as normalising blood chemistry. In diabetes mellitus types 1 and 2 (insulin-dependent and non-insulin-dependent), somatomedin-1 increases the sensitivity to insulin and improves glucose utilisation, and may contribute to healing of injured nerve tissue and improve renal function in humans. Adverse effects of somatomedin-1 appear to be related to overdosage. In conclusion, somatomedin-1 is an important hormone which has clinical roles as replacement therapy and other pharmacological therapies.

Child↗
PubMedDate not supplied

A multidisciplinary, comprehensive, ambulatory treatment scheme for diabetes mellitus in children.

A study has been carried out on 262 children with juvenile diabetes and their parents, treated up to 10 yr on an ambulatory basis by a multidisciplinary team composed of pediatric endocrinologist, nurse, dietitian, psychologist, and social worker. Comparison of the findings with those of a study performed before inception of the Counselling Center for Juvenile Diabetics revealed the following positive influences: the degree of control attained was both higher and sustained with greater regularity; there were fewer complications with no episodes of coma, brittle diabetes, or severe ketoacidosis and almost no need for hospitalization; the attitude of the affected child, his parents, and his teachers was found to be considerably improved; there was better understanding of the nature of the disease and its requirements; the child's motivation to maintain the diabetic regimen was greater and conflicts within the family circle were markedly reduced; the child's self-concept was much higher; and both scholastic achievements and social adjustment were greater. We concluded that psychological stability is a basic factor in the control of diabetes, and the value of the multidisciplinary approach in the treatment of this chronic disease is indicated.

Ambulatory Care↗