BACKGROUND: Osteopathy is a common clinical feature of chronic inflammatory bowel disease (IBD) in children and young adults at the time of primary diagnosis. The aim of the following study was to address the question of prevalance of a decreased bone density or increased bone metabolism in children with IBD. PATIENTS: We examined 63 patients (mean age 13 years; 5 - 18 years): 36 Crohn's disease (MC) patients, 16 colitis ulcerosa (CU) patient and one patient with colitis indeterminata (CID). 10 children who had been referred to the gastroenterological outpatient department due to suspected IBD symptoms were later found not to suffer from IBD. These 10 patients therefore were included in the study as controls. RESULTS: 8 of 10 CU patients and 18 of 28 MC patients showed a pathological bone density and abnormalities in bone metabolism. Repetitive bone density measurement was performed in 18 patients. In MC patients a - 0.39 SDS decrease of bone mineral density was found, without a simultaneous deterioration of clinical stage and inspite of a decreased cumulative prednisolon dosage. However in CU patients a + 0.06 SDS increase of bone mineral density was detected. These patients had a lower cumulative prednisolon dosage and a stable clinical course. CONCLUSIONS: In conclusion, pediatric IBD patients often show abnormalities in bone metabolism and decreased bone density. There is a need for multicentre, prospective randomised control trials to further identify therapeutic tools on the basis of the multifactorial etiology of bone disease in pediatric IBD patients.

Absorptiometry, Photon↗

PubMedDate not supplied

Cloning and sequencing of the complete cDNA encoding the human insulin receptor related receptor.

The insulin receptor related receptor (IRR) is a heterotetrameric transmembrane receptor with intrinsic tyrosine kinase activity. The IRR shares large homology with the insulin and the insulin-like growth factor-1 (IGF-I) receptor with regard to amino acid sequence and protein structure. So far, only a partial human sequence containing the complete 3' end has been reported, although the full-length human IRR cDNA had been used for transfection studies and functional analysis of the receptor. We have isolated a full-length human IRR cDNA and report on the 5' translated and untranslated region of the human IRR gene. The full length IRR sequence contains 4150 bases and shares a high degree of homology with the guinea pig IRR cDNA sequence and rat IRR sequences that had been reported earlier on by others. Sequencing of the IRR cDNA revealed that the human IRR cDNA contains 341 bases corresponding to the IRR 5' end in addition to the bases that had been reported on before. Also, this sequence contains the start codon of translation. The full length cDNA for the human IRR can now be used for functional expression studies and to elucidate the nature of the ligand for this receptor type.

Cloning, Molecular↗

PubMedDate not supplied

Effects of pure human follicle-stimulating hormone (pFSH) on sperm quality correlate with the hypophyseal response to gonadotrophin-releasing hormone (GnRH)

In 41 men with idiopathic infertility, the effect of pure follicle-stimulating hormone (pFSH) therapy on semen parameters was evaluated in relation to the results of the gonadotrophin-releasing hormone (GnRH) stimulation test in an open study. The patients showed a mean (+/-standard error) sperm concentration of 15.84 (+/-2.87) Mill. ml-1, 41.02 (+/-4.19)% of the spermatozoa were motile and 46.16 (+/-2.36)% normomorph before treatment. All patients were administered 150 IU pFSH subcutaneously three times weekly for 10 weeks. After therapy with pFSH, no significant differences compared with the pre-treatment sperm characteristics were observed (P > 0.05) except for the velocity average path, VAP (P = 0.029). However, the stimulation factors of FSH in the GnRH test showed a significantly negative correlation with the pFSH mediated improvement of sperm concentration (r = -0.662, P = 0.000002), of percentage of normomorph spermatozoa (r = -0.480, P = 0.0015) and total count of motile spermatozoa per ejaculate (r = -0.567, P = 0.00014). In consequence, the patients were divided into two groups depending on the stimulation factor of hypophyseal FSH secretion, FSH-SF. The cut-off point of the FSH-SF was set at 1.7 because the correlation analyses detected a 1.5-fold improvement of sperm parameters at this hypophyseal response on average. Pure FSH treatment increased the concentration of spermatozoa (P = 0.0007), the total count of motile spermatozoa in the ejaculate (P = 0.015) as well as the computer-aided sperm motion parameters VAP (P = 0.029) and velocity curve linear, VCL (P = 0.049) in patients with FSH-SF < 1.7, whereas in the patient group with FSH-SF > 1.7 no improvement of semen parameters was found. Insufficient stimulation of hypophyseal FSH secretion may be a prerequisite but not a guarantee for responsiveness to pFSH treatment. The results of the present investigation suggest that FSH stimulation in the GnRH test should be taken into account in idiopathic infertile men before pFSH therapy.

Adult↗

PubMedDate not supplied

Leptin as a metabolic regulator during fetal and neonatal life and in childhood and adolescence.

Body weight is regulated by a feedback loop in which peripheral signals report nutritional information to an integratory center in the brain. The cloning of the ob gene is consistent with this concept and suggests that body fat content in adult rodents is regulated by a negative feedback loop centered in the hypothalamus/1-8/. In a recent report, two severely obese children with congenital leptin deficiency due to a homozygous frame-shift mutation involving the deletion of a single guanine nucleotide in codon 133 of the ob gene have been described. This discovery provides the first genetic evidence that leptin is an important regulator of energy balance in humans. However, it has become increasingly clear that apart from leptin's function in the central nervous system and in regulation of energy balance, leptin also acts in the periphery and might be important as a hormone modulating processes in regard to reproduction, glucose metabolism and insulin resistance, as well as growth and development of many tissues and organs either directly or indirectly. This report reviews some of the topics of leptin research that are of particular importance and relevance for pediatric and adolescent medicine and for pediatric endocrinology in particular.

Adolescent↗

PubMedDate not supplied

Arginine infusion and/or acute changes of growth hormone levels do not acutely alter leptin serum levels.

UNLABELLED: Leptin, the ob gene product, is produced by differentiated adipocytes. It functions as an afferent signal to the central nervous system indicating satiety and fat mass status. It acts upon the hypothalamic-pituitary axis. Growth hormone (GH) secretion is thought to be stimulated by leptin. Conversely, leptin secretion and ob gene expression are regulated by classical neuroendocrine networks. Whether or not acute changes of GH concentrations directly alter leptin serum levels in vivo is still debated. We investigated whether or not acute changes in GH serum concentrations during arginine infusion (0.5 g/kg b. wt.) alter leptin serum levels in 45 children and adolescents (33 M, 12 F). GH and leptin serum levels were determined at -30, 0, 30, 60, 90, 120 min after arginine infusion using specific radioimmunoassays. Leptin serum concentrations remained unaltered throughout the arginine infusion in all children and adolescents whether or not GH secretion was normal. IN CONCLUSION: (1) Acute changes of GH levels do not alter leptin serum levels during acute arginine infusions over 120 min. (2) Arginine does not acutely modulate leptin secretion.

Adolescent↗

PubMedDate not supplied

[Obesity, malic enzyme and aging--an animal experiment study].

In male Wistar rats the influences of age and experimental obesity on the activity of malic enzyme (EC 1.1.1.40) in different organs were studied. Obesity was induced in newborn rats by injection of Na(+)-L-glutamate (2 mg/g b.w. daily) subcutaneously in the first 5 days. The enzyme activity was measured at the ages of 2, 6 and 18 months. In control animals the highest enzyme activities were found in the heart muscle, liver, epididymal fat pad and skeletal muscle after 6 months. After 18 months the activities in these organs are considerably reduced. In the kidneys the activity between the 2nd and the 18th months tends to decrease continuously and only the brain shows an opposite trend. In comparison with the control animals, in glutamate treated rats the enzyme activity doubles nearly in the lipogenic organs liver and fat tissue in all age groups. In liver and fat tissue of 6-month-old rats, previously treated with clonidine to stimulate growth hormone secretion, the activities are lower than in glutamate obese rats without clonidine, but still higher than in normal control animals. The qualification of glutamate obese rats as a model for the study of age-associated diseases like obesity or diabetes mellitus type II needs further investigation.

Adipose Tissue↗