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Biomedical subjects

B Klinger

Publications and source records attributed to B Klinger.

11 recordsLinked to original sources
PubMed1992

Effects of insulin-like growth factor on linear growth, head circumference, and body fat in patients with Laron-type dwarfism.

Patients with Laron-type dwarfism are clinically indistinguishable from those with isolated growth hormone (GH) deficiency, yet have high circulating GH concentrations associated with an inability to generate endogenous insulin-like growth factor I (IGF-I). Biosynthetic IGF-I was administered subcutaneously once daily for 3 to 10 months to 5 children with Laron-type dwarfism aged 3.3 to 14.5 years. There was a rapid stimulation of linear growth in body limbs, with a striking increase in head circumference, increased body weight, and a reduction in subcutaneous fat. Administration of IGF-I to patients with Laron-type dwarfism seems to have a beneficial effect on growth similar to that observed with long-term administration of GH in children with GH deficiency.

Adipose Tissue↗
PubMed1992

Growth hormone therapy in normal short children induces a transitory decrease in plasma growth hormone releasing hormone levels and in human growth hormone responsiveness to exogenous growth hormone releasing hormone.

A three-month study of the effect of growth hormone (hGH) therapy (0.1 U/kg/day sc) on plasma levels of GH releasing hormone (GHRH), somatostatin and insulin-like growth factor I (IGF-I) and on the hGH responsiveness to exogenous GHRH was carried out in 32 prepubertal short-stature children with normal GH secretion. Blood samples were collected prior to initiation of therapy, and at 5, 30 and 90 days of onset of therapy, as well as 2 and 90 days after termination of therapy. The nonconventional hGH therapy induced an increase in serum IGF-I levels which lasted as long as therapy was continued. Plasma GHRH levels showed an early transitory decrease after five days of therapy, whereas plasma somatostatin levels were unaltered. A slight suppression in hGH responsiveness to exogenous GHRH was found at 2 but not at 90 days after termination of hGH therapy. It is concluded that nonconventional hGH treatment does not cause permanent changes in physiological hGH secretion.

Adolescent↗
PubMed1992

IGF binding protein 3 in patients with Laron type dwarfism: effect of exogenous rIGF-I.

OBJECTIVE: The aim of the study was to investigate the serum levels of IGFBP-3, the major IGF-I binding protein, in patients with Laron type dwarfism (LTD) before and after IGF-I treatment. DESIGN AND PATIENTS: Eight Laron type dwarfism patients (four children and four adults) were treated for 7 days by one daily s.c. injection of biosynthetic IGF-I in doses of 120 or 150 micrograms/kg/day. MEASUREMENTS: Blood was sampled in the fasting state before and 1 and 7 days after the last injection. RESULTS: It was found that IGF-I administration significantly reduced plasma hGH levels with recovery after one week of no treatment. Serum IGFBP-3 was abnormally low (0.70 +/- 0.37 mg/l) and decreased significantly further during IGF-I treatment (to 0.48 +/- 0.28 mg/l) (P less than 0.065). CONCLUSIONS: The finding that serum IGFBP-3 is low in Laron type dwarfism, a disease due to molecular defects in the GH receptor, is compatible with the hypothesis that this IGF binding protein is GH-dependent. On the other hand the decrease during IGF-I administration and concomitant suppression of GH secretion may denote either that GH activity is not completely blocked in this syndrome or that there are additional mechanisms regulating IGFBP-3 synthesis.

Adolescent↗
PubMed1992

Serum prolactin in patients with Laron-type dwarfism: effect of insulin-like growth factor I.

Prolactin (PRL) secretion was studied in Laron-type dwarfism (LTD) patients (8 children and 9 adults) in basal condition, after acute insulin-like growth factor (IGF-I) or TRH injections and during 2 months of daily IGF-I treatment. Basal PRL was repeatedly higher (12.6 +/- 1.6 micrograms/l) than that in control subjects (7.6 +/- 1.2 micrograms/l, p < 0.05). Acute IGF-I injection caused an immediate slight decrease in serum PRL and growth hormone (GH), followed by a progressive rise to mean peak levels of 33.3 +/- 4.5 micrograms/l again parallel to serum hGH which rose to 86 +/- 20 micrograms/l--a response to the IGF-I-induced hypoglycemia. Intravenous TRH in LTD children induced a marked response in serum PRL, similar to that registered in estrogenized adult females. Serum PRL did not show consistent changes during chronic IGF-I treatment. It is suggested that the higher-than-normal PRL levels and release in LTD patients are due to a drift phenomenon of the mammosomatotropes which produce large amounts of hGH.

Adult↗
PubMed1992

Growth hormone and insulin-like growth factor regulate insulin-like growth factor-binding protein-1 in Laron type dwarfism, growth hormone deficiency and constitutional short stature.

Insulin-like growth factors (IGFs) mediate the effects of growth hormone (GH), and the insulin-like growth factor-binding proteins (IGFBPs) modulate the actions of IGFs in tissues. We studied the circulating levels of IGFBP-1 in 6 children and 9 adults with Laron type dwarfism (LTD), in 11 children and 21 adults with growth hormone deficiency (GHD), and in 8 children with constitutional short stature. Compared with the situation in healthy children, the basal serum IGFBP-1 concentration was 5.4-fold higher in LTD children, 4.1-fold higher in GHD children, and 3.8-fold higher in children with short stature (p < 0.02 vs controls in all groups). In adult patients with multiple pituitary hormone deficiency (MPHD), the IGFBP-1 concentration was 2-fold elevated, but it was normal in adult LTD patients. Intravenous (N = 10) or subcutaneous (N = 9) administration of IGF-I (75 micrograms.kg-1 and 150 micrograms.kg-1, respectively) in LTD children resulted in a rapid 50-60% fall in serum insulin (p < 0.02), a decline in blood glucose and a concomitant 40-60% rise of IGFBP-1 levels (p < 0.05). Treatment for seven days with IGF-I (150 micrograms.kg-1 x d-1) resulted in a decrease by 34% and 44% of serum IGFBP-1 level in two out of three children with LTD. After prolonged GH therapy, the IGFBP-1 level fell in GHD children by 29% (p < 0.05), in GHD adults by 52% (p < 0.02) and in children with constitutional short stature by 17% (p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effect of insulin-like growth factor I on the thyroid axis in patients with Laron-type dwarfism and healthy subjects.

We have evaluated the effect of exogenous administration of IGF-I on the thyroid axis in four separate studies: (1) iv bolus injection; (2) single sc injection; (3) seven days' sc treatment, and (4) four months' treatment. Thirteen patients with Laron-type dwarfism (LTD) participated in the investigations. In studies 1 and 2, 10 healthy subjects were also included. Before and during long-term treatment (study 4) six LTD patients underwent a TRH test. IGF-I was administered in a dose of 75 micrograms.kg-1 iv or 120-150 micrograms.kg-1 sc. Single injections of IGF-I caused significant decreases of serum TSH in LTD patients (iv: 1.7 +/- 0.2 to 1.1 +/- 0.1 mU/l; sc: from 2.1 +/- 0.4 to 1.1 +/- 0.2; p < 0.0005). In controls the decrease was for iv from 1.2 +/- 0.2 to 0.8 +/- 0.2 mU/l (p < 0.02) and for sc from 2.0 +/- 0.5 to 0.8 +/- 0.2 mU/l (p < 0.05). Long-term administration of IGF-I induces a transitory decrease of both serum TSH and fT4, followed by a spontaneous rise to pretreatment or even higher values. No changes in T3 were observed. TSH stimulation by TRH was significantly augmented after four months of IGF-I treatment (p < 0.005). The effects of IGF-I can be explained by an early stimulation of somatostatin release causing a decrease in TSH and followed by the development of compensatory mechanisms. All changes were within the normal ranges, not causing abnormal thyroid function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Biochemical and hormonal changes induced by one week of administration of rIGF-I to patients with Laron type dwarfism.

OBJECTIVE: The purpose of this investigation was to evaluate the effectiveness of short-term administration of recombinant biosynthetic IGF-I on patients with an hereditary inability to generate this hormone. DESIGN AND PATIENTS: Ten patients with Laron type dwarfism (LTD) (4 males, six females) aged 3 1/2 to 37 3/4 years were submitted to seven daily s.c. injections of recombinant IGF-I in doses of 120 or 150 micrograms/kg/day. MEASUREMENTS: Blood samples were drawn before, after three and seven injections, and one week after stopping the trial. RESULTS: The main biochemical and hormonal changes registered were (mean +/- SD): a marked rise in serum type III procollagen (PIIINP) from 4.2 +/- 0.9 to 7.3 +/- 2 micrograms/l (P less than 0.0003) and decrease in the following blood components: plasma hGH from 32.51 +/- 43.77 to 4.02 +/- 2.48 mU/l (P less than 0.001), serum cholesterol from 5.9 +/- 1 to 5.7 +/- 0.8 mmol/l (P less than 0.04), serum SGOT from 28.9 +/- 11.6 to 15.5 +/- 7.6 U/l (P less than 0.01) and serum LDH from 286 +/- 88 to 222 +/- 37 U/l (P less than 0.0005). The response of plasma insulin was variable, decreasing in seven of ten and increasing in three. Some of these effects were transitory, and were found after 3 days therapy but afterwards decreased (insulin, cholesterol and liver tests), others persisted throughout the whole treatment period (hGH, PIINP). CONCLUSIONS: IGF-I mimics the biochemical and hormonal changes described after administration of hGH. The administration of IGF-I in patients with Laron type dwarfism is devoid of side-effects and warrants assessment in long-term studies.

Adolescent↗
PubMed1991

Erythrocytes from patients with low serum concentrations of IGF-I have an increase in receptor sites for IGF-I.

The binding characteristics of insulin-like growth factor I on erythrocytes were studied in 11 patients with long-term IGF-I deprivation and low serum IGF-I levels. Six patients had Laron type dwarfism and 5 idiopathic isolated growth hormone deficiency, with a mean (+/- SEM) serum IGF-I level of 6.01 +/- 1.01 nmol/l as compared with that in 25 normal controls of 26.35 +/- 2.73 nmol/l (p = 0.00001). The mean (+/- SEM) [125I]IGF-I specific binding at a concentration of 4 x 10(12) cell/l was 12.11 +/- 1.29% for the patient group compared with 8.75 +/- 0.62% for the controls (p = 0.005). Scatchard analysis showed a curvilinear plot. Using a non-linear curve fit, the mean (+/- SEM) number of high-affinity receptor sites per cell was found to be 7.34 +/- 1.80 in the IGF-I-deprived patients and 2.84 +/- 0.29 in the controls (p = 0.0005). The mean +/- SEM dissociation constant was found to be 0.33 +/- 0.10 nmol/l for the patients and 0.26 +/- 0.08 nmol/l for the controls (NS). This study has demonstrated that the low serum concentration of IGF-I in Laron type dwarfism and isolated growth hormone deficiency is associated with an increase in receptor sites for IGF-I on the erythrocytes. The application of this property as a diagnostic acid remains to be established.

Adolescent↗
PubMed1990

Elimination characteristics of intravenously administered rIGF-I in Laron-type dwarfs.

The distribution and elimination characteristics (Ke alpha, Ke beta, t1/2) of an intravenous bolus of biosynthetic IGF-I administered to 10 patients with Laron-type dwarfism (LTD, 3 children and 7 adults) and 6 healthy volunteers (3 children and 3 adults) are reported. The mean (+/- SD) endogenous level of IGF-I in the LTD patients was 5.24 +/- 2.77 nM/l and in the controls 27.2 +/- 9.4 nM/l. In the LTD patients the mean elimination constant (Ke beta) was 0.004 +/- 0.001 min-1 and t1/2 = 2.6 +/- 0.7 h, whereas in the controls, Ke beta was 0.003 +/- 0.009 min-1 and the t1/2 = 4.4 +/- 0.5 h (p less than 0.05). The more rapid elimination of injected IGF-I in the LTD patients is assumed to be due to the absence of the GH-dependent 150 kDa IGF-I binding protein.

Adolescent↗
PubMed1990

Intravenous administration of recombinant IGF-I lowers serum GHRH and TSH.

Recombinant IGF-I was administered as an iv bolus of 75 micrograms/kg to 10 patients with Laron type dwarfism (3 children aged 9, 11 and 12 years and 7 adults aged 30.6 +/- 3.5 years) and to 8 healthy subjects (mean age 19.9 +/- 12.1 years) and determinations of IGF-I, GHRH, hGH, TSH, and glucose were made before and at 2, 5, 15, 30, 60, 90, and 120 min. The following effects were observed: a. an immediate, marked and sustained drop in blood glucose (p less than 0.001), more prolonged in the patients; b. in both groups, a dramatic rise in plasma hGH (p less than 0.01) which peaked at 60-90 min; in the patients this occurred after an initial immediate fall in plasma hGH (p less than 0.01); c. a progressive decrease of plasma GHRH and TSH (p less than 0.05, 0.02) in both patients and healthy controls. An hypothesis is put forward that acute and time-limited release of somatostatin by IGF-I is the main cause of the hormonal changes registered. As the IGF-I bolus also suppressed circulating insulin levels, the hypoglycemia is considered to be a direct effect of IGF-I.

Adult↗