Search PubMed⌕ Search

Biomedical subjects

Z Laron

Publications and source records attributed to Z Laron.

At least 55 records · Page 3Linked to original sources
PubMed1999

Lessons from recent epidemiological studies in type 1 childhood diabetes.

Recent studies have revealed that seasonality of onset of childhood insulin-dependent diabetes mellitus (IDDM) with a peak late in autumn and winter exists in populations with medium or high incidence of disease and parallels viral epidemics. In populations with low incidence no seasonality has been found, probably due to the development of tolerance towards the infectious agent(s). Analysis of the month of birth of children with IDDM showed a temporal shift with a peak in spring, but again only in populations with a medium or high incidence of childhood IDDM. This finding is suggestive of a transfer of virus infections from the mother to the fetus during the viral epidemic period. This unsymptomatic infection is assumed to cause the first pancreatic beta-cell damage which after subsequent damage leads to overt diabetes.

Child↗
PubMed1999

Natural history of the classical form of primary growth hormone (GH) resistance (Laron syndrome).

A description of the clinical, biochemical and endocrinological features of the classical form of the syndrome of primary growth hormone (GH) resistance (Laron syndrome) is presented including the progressive changes during follow-up from infancy into adulthood. The main diagnostic features are: severe growth retardation, acromicria, small gonads and genitalia, and obesity. Serum GH levels are elevated and insulin-like growth factor-I (IGF-I) values are low and do not rise upon stimulation by exogenous hGH. The pathogenesis of this syndrome is due to various molecular defects from exon deletion to nonsense, frameshift, splice and missense mutations in the GH receptor (GH-R) gene or in its post-receptor pathways.

Abnormalities, Multiple↗
PubMed1998

Interventional catheterization decreases plasma levels of atrial natriuretic peptide (ANP) in children with congenital heart defects.

Atrial natriuretic peptide (ANP) is one of the cardiac peptides implicated in volume and sodium homeostasis. We investigated the effect of interventional catheterization on plasma levels of ANP, aldosterone, and cortisol in 28 children with various congenital heart defects (CHD). Patients were divided by age into two groups: group A--infants and children over 3 months of age (n = 22), and group B--newborns (n = 6). These were compared to age-matched control groups. In group A, interventions included pulmonic valvotomy (n = 8), aortic valvotomy (n = 4), balloon angioplasty of native coarctation of the aorta (n = 3), balloon dilatation of the mitral valve (n = 1), and Rashkind double umbrella closure of patent ductus arteriosus (n = 6). Group B interventions included pulmonic valvotomy (n = 3), aortic valvotomy (n = 1), and balloon atrial septosomy (n = 2). In group A, mean ANP levels were markedly higher than in age-matched controls (125.2+/-15.8 vs. 24.6+/-4.6 pg/ml) (P <0.0001), and decreased immediately after intervention (75.6+/-11.4 pg/ml, P <0.02), and more markedly on follow-up (42.9+/-5.0 pg/ml, P < 0.0001). In group B (newborns), mean basal plasma levels were high before and after intervention and were not different from age-matched controls (243+/-42.1 vs. 220.8+/-16.2 pg/ml). There was a significant decrease on follow-up measurement (62.1+/-12.7 pg/ml, P < 0.005). In both groups, plasma cortisol levels increased significantly immediately following catheterization (P < 0.02), and normalized on follow-up. Basal aldosterone levels were normal in group A and high in Group B (9.9+/-3.8 vs. 167.6+/-16.9 ng/dl) (P < 0.001). It is suggested that plasma ANP levels are increased in children with CHD, without overt heart failure, and decrease significantly following successful intervention. In newborns with CHD, the physiological high ANP levels obscure the effect of the CHD.

Aldosterone↗
PubMed1998

Development of hyperandrogenism during treatment with insulin-like growth factor-I (IGF-I) in female patients with Laron syndrome.

OBJECTIVE: Patients with Laron syndrome (LS) can now be treated with recombinant IGF-I. We describe the development of androgenization during IGF-I treatment of female LS patients. PATIENTS: Six female patients with LS--two clinically prepubertal (11.6 and 13.8 years of age) and four young adults (30 to 39 years old)--underwent long-term replacement treatment with recombinant IGF-I. The daily doses were 150 micrograms/kg/day by subcutaneous (s.c.) injection in the girls and 120 micrograms/kg/day in the adult women. METHODS: Testosterone, delta 4-androstenedione, LH, FSH, insulin and IGF-I were determined by radioimmunoassay. Blood samples were obtained after an overnight fast before the IGF-I injection. Serum IGF-I was also determined 4 hours after the s.c. injections. RESULTS: During IGF-I treatment, four out of the six patients (two girls and two adults) developed progressive clinical symptoms and signs of hyperandrogenism (oligo/amenorrhoea and acne). Laboratory determinations showed a significant elevation in serum testosterone, delta 4-androstenedione and LH/FSH ratio. The hyperandrogenism occurred concomitantly with an increase in IGF-I serum and a decrease in serum insulin concentrations. Reduction in IGF-I dose or interruption in IGF-I treatment restored androgen levels to normal values. At the same time, the acne and oligomenorrhoea resolved. CONCLUSIONS: Overdosage of IGF-I can lead to androgenization, a previously undescribed undesirable effect of IGF-I. Long-term IGF-I treatment necessitates progressive adjustment of the IGF-I dose to avoid overtreatment.

Adolescent↗
PubMed1998

Lack of seasonality in the month of onset of childhood IDDM (0.7-15 years) in Shanghai, China.

A cohort of 136 children from Shanghai with insulin dependent diabetes mellitus (IDDM) (0.7-15 years) were analyzed for the month of onset of disease and month of birth. In contradistinction to populations with a medium or high incidence of IDDM, no seasonality was registered in the month of onset. On the other hand there was a significant (p < 0.026) seasonality in the month of birth (peak November to January), but which differed in pattern to that observed in populations with medium or high incidence. Our findings support the hypothesis that the initiation of IDDM is due to a viral infection and that one cause for the low incidence of childhood IDDM in certain populations is immunization against infectious pathogens in their early life.

Adolescent↗
PubMed1998

Effect of insulin-like growth factor-I treatment on serum androgens and testicular and penile size in males with Laron syndrome (primary growth hormone resistance).

Serum gonadotrophins. androgens, insulin and insulin-like growth factor-I (IGF-I) were determined before and during long-term treatment with recombinant IGF-I of seven males with Laron syndrome, and the changes correlated with changes in testicular volume and penile size. The subjects were four boys below the age of 5, two boys aged 10 and 14 but prepubertal and one 28-year-old fully sexually developed adult. IGF-I was administered by a once daily subcutaneous injection of 150 microg/kg per day to the boys and 120 microg/kg per day to the adult patient. In the very young boys no change in serum gonadotrophins, androgens, gonads or genitals was registered. In the two older boys and the adult patient, there was a progressive rise in luteinizing hormone, follicle-stimulating hormone and testosterone. Concomitantly, there was an increase in size of the testes and penile length. The two boys started puberty. As very high serum IGF-I levels were registered in the adult patient, the daily dose was progressively decreased to 70 microg/kg per day. Stopping the IGF-I administration in this patient, according to the protocol, led to a return to pretreatment serum levels and testicular and penile size. This report shows for the first time a direct effect of IGF-I on sex hormones and sex organs in the male.

Adolescent↗
PubMed1997

The development and progression of diabetic retinopathy in type I diabetic patients: a cohort study.

To describe the course and risk factors for development and progression of retinopathy, we studied a cohort of 333 Israeli Jewish patients with Type 1 (insulin-dependent) diabetes mellitus. The median age at diagnosis was 9.5 (range 0.04-26.2) years and the median duration of follow-up was 14 (range 1.6-30) years. Evaluation of both retinae was performed yearly since referral and HbA1 values were tested every 3 months since 1978. During a follow-up of 4070 patient-years, 162 patients developed non-proliferative retinopathy. The median retinopathy-free interval was 14.9 years and after 30 years all patients were affected. Pre-pubertal duration of diabetes was relevant. Independent and significant risk factors for early onset of non-proliferative retinopathy were: poor cumulative glycaemic control (median retinopathy-free interval in the 1st vs 4th quartiles of mean HbA1 values over all years: 18.0 vs 12.5 years, p = 0.0001); onset of diabetes during or after puberty (median retinopathy-free interval in patients with onset of diabetes before, during or after pubescence: 16.3, 13.2 and 14.0 years, respectively, p = 0.0001); and non-Ashkenazi Jewish origin (median retinopathy-free interval 15.8 years in Ashkenazi vs 14.0 in non-Ashkenazi patients, p = 0.0004). Of 162 patients with non-proliferative retinopathy, progression to proliferative retinopathy occurred in 37, during 707 patient-years. The first event of proliferative retinopathy was diagnosed within the 1st year after non-proliferative retinopathy evolved, and at 6.3 years since onset of non-proliferative retinopathy 75% of the patients were still free of proliferative changes. Risk factors significantly and independently associated with an early progression to the proliferative stage were: poor glycaemic control in the last 3 years prior to the development of proliferative retinopathy and non-Ashkenazi Jewish origin. All patients in the 4th quartile of HbA1 values were affected by proliferative retinopathy within 11.6 years after onset of non-proliferative retinopathy.

Adolescent↗
PubMed1997

Increased number of IGF-I receptors on erythrocytes of women with polycystic ovarian syndrome.

OBJECTIVE: To test the hypothesis that insulin acts though ovarian IGF-I receptors to produce excessive amounts of androgens in polycystic ovarian syndrome (PCOS), by measuring the binding capacity of IGF-I receptors on erythrocytes and relating the findings to the degree of hyperandrogenism and hyperinsulinaemia. DESIGN: A case-control study of IGF-I receptors on erythrocytes of women with PCOS and age- and weight-matched controls. PATIENTS AND METHODS: IGF-I receptors on erythrocytes, serum levels of androgens, IGF-I, GH, basal insulin and insulin response during oral glucose tolerance test (oGTT) were measured after induced or spontaneous withdrawal bleeding in 10 women with PCOS and eight normo-ovulatory women. RESULTS: An increased number of IGF-I receptors was found on erythrocytes of patients with PCOS compared with the controls (P < 0.01), irrespective of their body mass index. Serum IGF-I levels were similar in both groups. The degree of hyperinsulinaemia, provoked by oGTT, correlated positively with basal insulin (r = 0.69; P = 0.003), but not with the number of IGF-I receptors. However, the number of IGF-I receptors correlated positively with androstenedione (r = 0.54, P = 0.0018). CONCLUSIONS: The findings in the present study that the number of IGF-I receptors and not the insulin levels correlate with serum androstenedione support the theory that the hyperandrogenism in PCOS is not a direct effect of the hyperinsulinaemia, but IGF-I mediated.

Adolescent↗
PubMed1997

Muscle force and endurance in untreated and human growth hormone or insulin-like growth factor-I-treated patients with growth hormone deficiency or Laron syndrome.

Muscle force and endurance of four muscle groups (biceps, triceps, hamstrings and quadriceps) were measured by a computerized device in three groups: (A) 4 boys with isolated growth hormone deficiencies (IGHD) examined before at 10 and 24 months of hGH treatment; (B) 5 children (2 F, 3 M) with Laron syndrome were examined 3.5-4 years after initiation of insulin-like growth factor-I (IGF-I) treatment, and (C) comprised 8 untreated adults (5 F, 3 M) with Laron syndrome. For each patient, 2 matched controls, by age, sex, physical activity and height below the 50th percentile, were examined. GH- or IGF-I-deficient patients before treatment revealed reduced muscle force and endurance. GH treatment (0.6 U/kg/week) restored muscle force and endurance, progressively, mainly in the boys with puberty. Three to 4 years of IGF-I treatment (150 micrograms/kg/day) in patients with Laron syndrome proved to have a weaker effect than GH in restoring muscle force. The difference in effectiveness between hGH and IGF-I in restoring muscle force may be due to either the more marked muscle underdevelopment in Laron syndrome patients than in patients with IGHD or a difference in action potential between the two hormones.

Adolescent↗
PubMed1997

Final height of girls with central precocious puberty, untreated versus treated with cyproterone acetate or GnRH analogue. A comparative study with re-evaluation of predictions by the Bayley-Pinneau method.

This study was designed to determine the benefit of therapy on final height (FHt) in girls with central precocious puberty (CPP). A total of 102 patients were evaluated--28 untreated, 26 treated with cyproterone acetate (CyA), and 48 treated with GnRH analogue (GnRHA)-and their achieved FHt was compared to the respective target height (THt). Of the untreated girls, half (14/28) had a slow course of puberty and reached THt +/- 0.5 SD (FHt 160.2 +/- 7.1, THt 159.5 +/- 6.6 cm); the other half (14/28) had an accelerated course of puberty with a FHt well below THt (FHt 150.8 +/- 4.3, THt, 159.2 +/- 5.9 cm) and in most cases (14/28) below the height-SDS of both parents. The treated girls (both regimens) reached THt above (CyA group: FHt 157.8 +/- 5.1, THt 156.8 +/- 5.1 cm; GnRHA group: 159.6 +/- 6.3, THt 157.7 +/- 5.7 cm). We conclude that without treatment the FHt of girls with CPP may be significantly compromised and that therapy is more beneficial if started before bone age exceeds 12 years. Our data also showed that for final height predictions in CPP the Bayley and Pinneau tables for average children should be used, regardless of the advanced bone age of the patients.

Administration, Oral↗