ISSN:1663-2818    

DOI:10.1159/000184297

出版商:S. Karger AG    

年代:1995

数据来源: Karger

ISSN:1663-2818    

DOI:10.1159/000184299

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Anti-Müllerian hormone (AMH), a member of the transforming growth factor family also called Müllerian-inhibiting substance or factor, is produced by immature Sertoli cells and, in much smaller amounts, by postnatal granulosa cells. Its paediatric applications are essentially diagnostic. Measurement of AMH concentration in serum by an enzyme-linked immunosorbent assay does not require prior gonadal stimulation and is useful to detect the presence of testicular tissue and assess its function before puberty. The assay can easily differentiate between bilateral cryptorchidism and anorchia and discriminates between non-adrenal female pseudohermaphroditism and true hermaphroditism, although in the latter condition, the serum AMH concentration is usually low because of testicular dysgenesis. After puberty, AMH becomes low or undetectable, due to down-regulation of AMH production by testosterone. This does not occur in androgen-insensitive patients. A rare form of male pseudohermaphroditism, the persistent Müllerian duct syndrome, characterized by the persistence of a uterus and tubes in otherwise normally virilized males, is due to defects in genes coding for AMH or its receptor. Measurement of serum AMH concentration discriminates between the two aetiological forms of the syndro

ISSN:1663-2818    

DOI:10.1159/000184300

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

There is increasing awareness that growth hormone (GH) replacement therapy is also essential in adult patients with growth hormone deficiency (GHD). There are little data available on the dose requirements for replacement therapy in this age group. In childhood, the growth response to GH therapy can serve as an indicator for the correct replacement dose. Because this indicator does not exist in adults, we analyzed growth factors and biochemical markers of bone metabolism by specific radioimmunoassays in a group (n = 12) of adult patients (age, 20.0-31.6 years) with GHD with childhood onset before and after a 4-week treatment period (daily, s.c.) with recombinant, human GH at different doses (0.125, 0.25 and 0.5 IU/kg body weight/week). Comparing the basal levels to those on low-dose GH (0.125 IU/kg/week) and on a high dose (0.5 IU/kg/week), the following results were obtained. Insulin-like growth factor-I (IGF-1) in serum: basal, 68.6 ± 37 ng/ml; low dose, 176.9 ± 65 ng/ml (p ≤ 0.05); high dose, 380.6 ± 200 ng/ml (p < 0.01). IGF-binding protein-3 in serum: basal, 2.13 ± 0.58 mg/l; low dose, 3.23 ± 0.84 mg/l (p < 0.01); high dose, 3.97 ± 0.82 mg/l. Osteocalcin in serum: basal, 3.88 ± 1.27 ng/ml; low dose, 7.01 ± 2.20 ng/ml (p < 0.01); no further increase. Procollagen-I peptide in serum: basal, 113.6 ± 36.7 μg/l; low dose, 211.6 ± 90.4 μg/l (p < 0.01); no further increase. Galactosylhydroxylysine excretion in urine: basal, 12.9 ± 5.24 μmol/g; low dose, 23.3 ± 13.2μmol/g(p < 0.05); high dose, 27.7 ± 13.7 μmol/g. We conclude that the parameters measured possibly represent a useful tool for the assessment of the correct replacement dose in adult GHD. As the lowest dose investigated (0.125 IU/kg body weight/week) normalized serum levels of growth factors and parameters of bone metabolism, this dose might be the advisable replacemen

ISSN:1663-2818    

DOI:10.1159/000184302

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

In adult patients with growth hormone deficiency, the fatty acid composition of abdominal and gluteal fat tissues was determined prior to and at several time points after administration of recombinant human growth hormone. Values obtained before growth hormone treatment were not different from those seen in a normal population. However, as in healthy individuals, significant differences were found in the composition of the fat sampled at the different sites. Administration of growth hormone had no effect on the composition. It is concluded that a change in fatty acid composition of fat tissue is unlikely to be a factor contributing to the reported increased cardiovascular mortality in hypopituitarism and that treatment with recombinant human growth hormone has no effect on that potential cardiovascular risk factor.

ISSN:1663-2818    

DOI:10.1159/000184304

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

We measured the ratio of GH by radioreceptor assay (RRA) using IM-9 cells to its radioimmunoassay (RIA) level in: (a) 25 children and young adults with normal growth (controls); (b) 7 poorly growing children with GH neurosecretory dysfunction (GHND) who had normal stimulated GH but subnormal integrated concentration of GH (IC-GH) who responded to GH therapy; (c) 4 poorly growing children who had both normal stimulated GH and IC-GH but did not respond to GH therapy (GHNR – GH nonresponder), and (d) 7 poorly growing patients with normal stimulated, and IC-GH who responded to GH therapy (GHR – GH responder). The RRA/RIA ratio of the GHND group was 1.3 ± 0.4 similar to that of the control group- 1.3 ± 0.3. The mean RRA/RIA ratio of the 7 GHR patients was 0.6 ± 0.5, significantly lower than the controls and the GHND patients (p < 0.05). The RRA/RIA ratios of the 4 GHNR patients was not different from the controls. We conclude that: (1) GH binding is normal in GHNR and GHND patients and (2) RRA/RIA ratio below the normal range as measured by IM-9 cell GH RRA in short, poorly growing children with normal GH secretion, was a predictor of the response to GH t

ISSN:1663-2818    

DOI:10.1159/000184306

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The objective of this study was to examine the changes in basal plasma gonadotropin, α-subunit, sex steroid, and prolactin levels and the prolactin and luteinizing hormone (LH) secretion pattern before, during and 161 days after treatment with a depot preparation of D-Trp-6-GnRH in young men. Gonadotropins, α-subunit, sex steroids, and prolactin were measured in pooled plasma samples. Additionally, before treatment, several times during its course and on day 161 after treatment, blood samples were drawn for 8h every 15 min for prolactin and LH measurements. After initial stimulation of the pituitary, administration of a depot preparation of D-Trp-6-GnRH resulted in a constant decrease in gonadotropin and sex steroid concentrations with LH and testosterone concentrations remaining within the limits of prepubertal levels from days 16 to 48. α-Subunit concentrations (0.4 ± 0.09 IU/l; mean ± SE) increased after application of D-Trp-6-GnRH, and remained elevated until day 48. Basal prolactin levels (3.5 ± 0.25 μg/l) did not change significantly during treatment but afterwards increased consistently with maximal levels at day 141 (15.3 ± 3.8 μg/l); they had decreased at day 161 to 10.3 ± 1.8 μg/l which is significantly higher than before treatment (p < 0.05). On day 161, prolactin pulse amplitude was significantly higher than before and during treatment (p < 0.05), while no significant changes in pulse frequency occurred. No significant temporal coupling between LH and prolactin release could be detected. In conclusion, after administration of a depot preparation of D-Trp-6-GnRH to 6 young men, there was a rise in basal prolactin levels and prolactin pulse amplitude as a long-term side effect of treatment, with maximal levels at 141 days after a

ISSN:1663-2818    

DOI:10.1159/000184307

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

We have identified subtle abnormalities of thyroid function and glucose control in patients with Rett syndrome. The mean serum total thyroxine (T4) concentration was significantly lower in a group of subjects with Rett syndrome (6.9 ± 1.5 μg/dl, n = 34; p < 0.0001) than the adult reference range (8.5 ± 1.75 μg/dl, n = 200). This difference remained significant even for the 17 subjects not taking anticonvulsants (7.6 ± 1.5 μg/dl; p < 0.05 vs. adult reference). The difference was more marked when compared to age-adjusted normals, with 10 subjects having a serum total T4 concentration below normal for age including 3 of 17 of the subjects not taking anticonvulsants. This decrease in serum total T4 concentration was not due to changes in binding proteins as measured by 3,5,3’-triiodothyronine resin uptake, and was associated with a decreased concentration of thyroid-stimulating hormone (1.7 ± 1.6 mU/l, n = 23 vs. 2.5 ± 1.0 mU/l, n = 200; p < 0.01). Oral glucose tolerance tests were performed in 10 of the subjects with Rett syndrome. They had a delay in the peak glucose and insulin concentrations. Glucose levels were elevated at 1 and 2 hours (p < 0.05), and insulin levels were elevated at 1, 2, and 3 hours (p < 0.05). Two subjects fulfilled criteria for impaired glucose

ISSN:1663-2818    

DOI:10.1159/000184309

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Basal serum concentrations of cortisol, dehydroepiandrosterone (DHA) and its sulfate (DHAS), 4-androstene-3,17-dione (A4) and 17α-hydroxyprogesterone (17OHP) were measured yearly in children treated with bone marrow transplantation (BMT) with or without preceding total body irradiation (TBI). Age-matched controls were used for comparison. ACTH stimulation tests were performed in the patients before and after treatment. However, in the samples taken before BMT only cortisol was measured. Basal posttreatment cortisol levels were subnormal in TBI-treated boys (n = 14, aged 5-17 years at BMT) during the adrenarcheal period (7-14 years) but became normal afterwards. All other groups had normal cortisol values. Treatment neither affected basal levels nor the ACTH-induced increment (δ-value) of cortisol. In the boys treated with TBI, normal basal levels of 17OHP and adrenal androgens were found with the exception of decreased DHA levels in the postadrenarcheal boys. However, the δ-17OHP values had an abnormal age relation and were significantly higher than in the patients not treated with TBI. In the patients not treated with TBI (6 boys aged 2-17 years) normal responses were found for 5 years or more after treatment. In female patients treated with TBI (n = 12, aged 1-16 years) circulating levels of DHA, DHAS and A4 were significantly decreased up to 5 years or more following treatment. It is concluded that after TBI, the cortisol homeostasis is maintained at the cost of reduced adrenal androgen secret

ISSN:1663-2818    

DOI:10.1159/000184311

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

This study evaluated the effect of insulin on the respiratory burst of human polymorphonuclear leukocytes (PMNLs) and the signalling pathways involved in this process, especially the involvement of protein kinase C (PKC). Isolated human PMNLs from healthy volunteers were incubated with different concentrations of insulin (10-10-10-7 mol/l) and for different durations of incubation (5-90 min). The intracellular production of hydrogen peroxide (H2O2) was detected employing a previously validated flow cytometric assay using 2’,7’-dichlorofluorescein-diacetate (DCFH-DA) as a marker for H2O2 production. Specificity of insulin action was verified using an insulin antagonist (the monoclonal antibody MA-10). To identify the signalling pathway involved, we used: (a) monoclonal antibody MA-5, directed against the α-subunit of the insulin receptor, that partially mimics insulin without activating tyrosine kinase; (b) H7, an inhibitor of PKC involved in O2- production in PMNLs, and (c) phorbol myristate acetate (PMA) that binds and stimulates PKC. Insulin caused a dose- and time-dependent stimulation of H2O2 release by human PMNLs. The effect of insulin was blocked by MA-10. The actions of insulin and PMA on H2O2 release were additive, whereas the actions of MA-5 and PMA were not. H7 partially inhibited the H2O2 production stimulated by insulin and completely inhibited MA-5 action. We conclude that insulin stimulates, in a dose- and time-related manner, the respiratory burst of human PMNLs. PKC activation can only partially account for the intracellular mechanisms involved in this pro

ISSN:1663-2818    

DOI:10.1159/000184313

出版商:S. Karger AG    

年代:1995

数据来源: Karger