[Considerations on changes in the demand on nurses in future pediatrics].
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Biomedical subjects
Publications and source records attributed to W Teller.
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Recent studies demonstrated significantly higher serum leptin concentrations in females as compared with males, even after correction for differences in body fat mass. The aim of our study was to measure serum leptin concentrations in a large group of obese children and adolescents to determine the possible role of sex steroid hormones on both leptin serum concentrations and production in human adipocytes. Obese girls were found to have significantly higher leptin concentrations than boys at the same degree of adiposity (25.2+/-14.1 vs. 17.2+/-12.6 ng/ml, P < 0.001). In a multiple regression analysis with age and body mass index (percent body fat) as fixed variables, it turned out that testosterone had a potent negative effect on serum leptin in boys, but not in girls. In vitro experiments using newly developed human adipocytes in primary culture showed that both testosterone and its biologically active metabolite dihydrotestosterone are able to reduce leptin secretion into the culture medium by up to 62%. Using a semiquantitative reverse transcriptase-PCR method, testosterone was found to suppress leptin mRNA to a similar extent. These results suggest that, apart from differences in body fat mass, the higher androgen concentrations in obese boys are responsible for the lower leptin serum concentrations compared with obese girls.
The purpose of this study was the evaluation of a predictive genetic marker for nephropathy and hypertension in patients with type-I-diabetes mellitus (IDDM). The study was performed on 247 pediatric patients with IDDM. The mean age was 15.5 years (range 3.1-29.3), the mean duration of diabetes was 7.6 years (range 0.1-25.7). Age-related blood pressure and nocturnal albumin excretion rate were compared with the insertion/deletion-(I/D) polymorphism of the angiotensin-I converting enzyme gene. The genotype distribution did not differ significantly between IDDM patients (ID 48%, D 28%, I 24%) and the control group (ID 44%, D 37%, I 19%). Neither in the entire group, nor in patients with IDDM for more than 5 years, was a correlation found bet-ween allele distribution and albumin excretion rate. No correlation was found between genotype and blood pressure. When patients with a chronological age above 12 years were analysed separately, the genotype distribution between the groups with normal and elevated blood pressure showed no significant difference. The previously reported association of the I/D-polymorphism with nephropathy could not be confirmed in this study. The development of microalbuminuria, nephropathy and hypertension will be followed in our pediatric patients.
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The aim of the present study was to develop an equation for the prediction of total body water (TBW) from bioelectrical impedance analysis (BIA) in obese children and adolescents before and after weight reduction. In 146 obese subjects with a mean age of 12.7 +/- 3.0 y (5.5-17.8 y), TBW was measured by using deuterium dilution as well as the resistance index (RI; ht2/resistance) using BIA before and after weight loss. Initially, the RI correlated well with measured TBW (r2 = 0.92, P < 0.001). A multiple-regression analysis using forward stepwise selection of the variables RI, sex, age, weight, height, and waist-hip ratio revealed that the equation TBW = 0.35 x RI + 0.27 x age + 0.14 x weight - 0.12 predicts most accurately individual values of TBW before weight loss (adjusted r2 = 0.96, SEE = 1.9 L) with a mean error of predicted TBW of 1.40 +/- 1.38 L. This equation was validated in 1000 random samples (bootstrap-sampling method), giving a mean r2 of 0.95. During the weight-reduction program, which included an energy-restricted diet and an extensive exercise program, the patients lost 7.7 +/- 3.2 kg, leading to a small decrease in TBW of 0.4 +/- 1.5 L. When the developed prediction equation was applied to the data after weight loss, an r2 value of 0.94 between measured and calculated TBW and a mean error of 2.18 +/- 1.89 L was obtained. Validation of the equation in 1000 random samples after weight loss again gave a mean r2 value of 0.95. Individual changes in predicted TBW correlated only weakly with those of measured TBW (r = 0.21, P < 0.05). Thus, individual TBW values before and after weight loss can be predicted by BIA with acceptable accuracy by using the developed equation. However, prediction of small individual changes in TBW during weight loss is not possible by BIA.
The aim of this study was to investigate the regulation of leptin expression and production in cultured human adipocytes using the model of in vitro differentiated human adipocytes. Freshly isolated human preadipocytes did not exhibit significant leptin mRNA and protein levels as assessed by reverse transcriptase (RT)-polymerase chain reaction (PCR) and radioimmunoassay (RIA). However, during differentiation induced by a defined adipogenic serum-free medium, cellular leptin mRNA and leptin protein released into the medium increased considerably in accordance with the cellular lipid accumulation. In fully differentiated human fat cells, insulin provoked a dose-dependent rise in leptin protein. Cortisol at a near physiological concentration of 10(-8) mol/l was found to potentiate this insulin effect by almost threefold. Removal of insulin and cortisol, respectively, was followed by a rapid decrease in leptin expression, which was reversible after readdition of the hormones. These results clearly indicate that both insulin and cortisol are potent and possibly physiological regulators of leptin expression in human adipose tissue.
OBJECTIVE: To investigate serum concentrations of insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) in obese adolescent girls before and after weight reduction and to examine their associations with hormonal and metabolic parameters. PATIENTS AND METHODS: 73 girls (age: 15.0 +/- 1.1 y, BMI: 31.1 +/- 3.8 kg/m2) participated in this 6 w intervention study. RESULTS: (1) Compared to 100 normal-weight girls of same age the obese subjects had increased levels of IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3 and normal levels of IGF-II. (2) After weight loss (8.1 +/- 2.0 kg) IGF-II and IGFBP-2 increased and IGF-I, IGFBP-1, IGFBP-3 and the ratio IGF-I/IGFBP-3 decreased significantly. (3) Correlation analysis revealed that fasting insulin levels of the patients were positively correlated with IGF-I but inversely with IGFBP-1 and IGFBP-2. IGFBP-2 was associated with several metabolic parameters: it showed an inverse correlation with uric acid and triglyceride levels. The ratio IGFBP-2 to IGFBP-1 was inversely correlated with total cholesterol and LDL-cholesterol. In addition, IGFBP-2 was inversely correlated with the waist-to-hip ratio of the girls. CONCLUSIONS: These studies of a homogeneous group of patients give further insight into possible physiological regulations and roles of IGFs and IGFBPs. The main conclusion is that obesity has to be considered for interpretation of serum concentrations of IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3. Furthermore, out results suggest that (i) the decrease in IGF-I/IGFBP-3 after weight loss could be partly responsible for the impaired growth velocity seen in obese children during hypocaloric feeding and (ii) low IGFBP-2 and high IGFBP-1 levels are associated with an unfavorable atherogenic risk factor profile.
The aim of this study was to investigate the role of body fat distribution on steroid hormone serum concentrations in obese adolescent girls before and after weight reduction. Ninety-two girls (age, 15.1 +/- 0.7 yr) with a mean body mass index of 31.2 +/- 4.6 kg/m2 participated in this 6-week intervention study. Initially, girls with abdominal obesity (waist to hip ratio, > 0.86; n = 30) had higher levels of total and free testosterone and lower levels of sex hormone-binding globulin as well as lower morning levels of total and free cortisol than girls with gluteal-femoral obesity (waist to hip ratio, < 0.80; n = 31) independent of their body mass index. After a mean weight loss of 8.3 +/- 2.6 kg by a standardized weight loss program, significant reductions were observed in estradiol, total and free testosterone, dehydroepiandrosterone sulfate, and the ratio of LH to FSH, whereas sex hormone-binding globulin and free cortisol levels increased significantly. Decreases in total and free testosterone and increases in total and free cortisol were significantly greater in the girls with abdominal obesity than in the girls with gluteal-femoral obesity. Our results suggest that obese girls with an abdominal pattern of fat distribution exhibit more pronounced steroid hormone aberrations, in particular a high androgenic activity, than girls with a gluteal-femoral pattern of fat distribution. The reduction of excess body weight by a conventional treatment regimen is associated with a remarkable improvement of steroid hormone abnormalities in this particular subtype of obese adolescent girls.
The information available on the medical and psychosocial status of patients with Turner syndrome beyond the paediatric age group is scarce. We therefore studied 25 unselected women with cytogenetically proven Turner syndrome (age 20-50 years), who never received any growth-promoting therapy, and ten control women (25-48 years). In addition to anthropometric measurements, an oral glucose tolerance test was performed, auto-antibodies to endocrine tissues were studied, bone mineral density of the forearm was measured by single photon densitometry, and information about the psychosocial distress of the patients was obtained. Adult height averaged 148.7 +/- 1.1 cm (mean +/- SE), which was 16 cm below the mean of adult women from a similar background. In Turner patients, final height correlated significantly with mid-parental height (final height = 0.67 x MPH + 32.1; r = 0.69). Body mass index was increased in Turner patients (25.6 +/- 1.3 kg/m2) compared to controls (21.4 +/- 0.6; P < 0.006). Six patients (25%) had impaired glucose tolerance or overt diabetes mellitus (one patient). Insulin release was augmented but delayed in the Turner group, and the area under the insulin stimulation curve was correlated to body mass index (r = +0.54, P < 0.01). Thyroid antibodies were detected in nine patients (37.5%). On average, bone density of the forearm was only marginally reduced compared to the age-dependent normal range. All women were employed, while only one of the Turner women was married. As a group, the subjects expressed greater distress due to infertility compared to short stature.(ABSTRACT TRUNCATED AT 250 WORDS)
We examined the effect of the pattern of body-fat distribution on the modification of atherogenic risk factors in obese adolescent girls during weight reduction. During the 6-wk program, which included a mixed diet of 4321 kJ/d and intensive physical exercise, the girls lost 8.5 +/- 2.4 kg and their waist-to-hip ratio (WHR) decreased from 0.86 +/- 0.05 to 0.81 +/- 0.05 (P < 0.01). Significant reductions were observed for total cholesterol, LDL cholesterol, uric acid, fasting insulin, and systolic and diastolic blood pressure. Girls with abdominal obesity (WHR > 0.88) had greater reductions in serum cholesterol, LDL cholesterol, and uric acid than did girls with gluteal-femoral obesity (WHR < 0.81). In a multivariate-regression analysis these differences could be partly explained by the greater weight loss of the girls with abdominal obesity. These results suggest that during weight reduction girls with abdominal obesity exhibit more beneficial changes in the atherogenic-risk-factor profile than do girls with gluteal-femoral obesity, partly because of a greater weight loss.
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We studied the influence of transforming growth factor beta (TGF-beta) on cultured bone cells derived from two patients with osteogenesis imperfecta (OI) and from human controls. Additionally, cells from a hyperplastic callus that had developed spontaneously at the femur of the patient in Case 1 and cells from a normal fracture callus were included in the study. TGF-beta increased the synthesis of total protein and collagen of all cells without changing the pattern of interstitial collagens. Proliferation was stimulated by TGF-beta in the OI bone cells from Case 1, in cells from the central part of the hyperplastic callus, and in cells from the fracture callus. In Case 2, proliferation of bone cells was decreased by low concentrations of TGF-beta. Alkaline phosphatase (AP) activity was enhanced by TGF-beta in normal human bone cells, not affected in bone cells from the patient in Case 2 or in cells from the central part of the hyperplastic callus, and inhibited in bone cells and cells from the peripheral part of the hyperplastic callus of Case 1 and in cells from the fracture callus. We conclude that TGF-beta has common and specific effects on cultured human cells derived from different types of skeletal tissues. Simultaneous stimulation of collagen synthesis and AP activity by TGF-beta was restricted to normal human bone cells and might reflect their mature state of osteoblastic differentiation. Cells derived from bone of both patients with OI, from the hyperplastic callus, and from the fracture callus showed a different response pattern to TGF-beta.(ABSTRACT TRUNCATED AT 250 WORDS)
A severely ill 2-month-old female infant was admitted with meningitis and septicaemia caused by Streptococcus pneumoniae. The patient, who also had an acute cytomegalovirus (CMV) infection, revealed the typical clinical and biochemical characteristics of type I tyrosinaemia (TIT). Clinical evidence of severe hepatocellular damage was shown, but urinary succinylacetone was not detected. The diagnosis of TIT was finally confirmed by decreased activity of fumarylacetoacetase (FAA) in skin fibroblasts from the patient and both parents. Following dietary treatment and after overcoming the bacterial and viral infection, the patient's liver function improved.
Recent studies have demonstrated an association between the pattern of body fat distribution and the occurrence of cardiovascular risk factors. In this study, we evaluated changes in body fat distribution as defined by several anthropometric criteria during a six week weight reduction programme in 110 obese adolescent girls (mean age 15.2 +/- 0.4 years). The standardized regimen included a mixed diet of 1032 kcal/day and a daily exercise programme of 1-2 h duration. The mean weight loss was 8.6 +/- 2.8 kg, decreasing the body mass index (BMI) from 31.4 +/- 4.7 to 28.2 +/- 4.9 kg/m2 (P < 0.01). The reduction in body weight was accompanied by a significant decrease in the waist-to-hip ratio (WHR) from 0.86 +/- 0.06 to 0.81 +/- 0.05 (P < 0.01). The initial WHR was correlated with the degree of weight loss independent of the initial weight (r = 0.34, P < 0.001). Categorized according to the waist-to-hip ratio girls in the upper tertile (WHR > 0.88) lost significantly more weight than girls in the lower tertile (WHR < 0.80) (9.8 +/- 2.7 vs. 6.8 +/- 2.5 kg, P < 0.01). These findings suggest that girls with an abdominal type of obesity benefit more from a weight reduction programme than girls with a gluteal-femoral type of obesity.
Brain neurotransmitters play an essential role in central regulation of hypothalamic factors which stimulate or inhibit the secretion of pituitary hormones. Insight in this complex system might be obtained by analysing changes in pituitary and peripheral hormone secretion following the administration of neuroactive drugs which influence the action of neurotransmitters. Desipramine is well-known to inhibit presynaptic norepinephrine reuptake, clomipramine on the other hand interferes with the serotoninergic system. In 15 male volunteers, the effects of single-dose administration of each drug were studied in comparison to placebo. Basal concentrations of ACTH and cortisol, as well as the rise of both hormones following insulin-induced hypoglycemia, were studied. Basal cortisol values and the response to hypoglycemia were not affected by either pharmacon in this study. Slight differences could be seen in the ACTH responses, which were however not significant.
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The insulin secretory capacity was examined in diabetic children at the time of partial clinical remission during which their condition could be managed with low insulin therapy (less than 0.5 U insulin/kg body weight) and no urinary glucose excretion. The extent of the residual beta cell function in 26 children was assessed either by an i.v. arginine test, a combined i.v. glucose-i.v. arginine test, a combined i.v. tolbutamide-i.v. arginine test, or a combined oral glucose-i.v. arginine test determining the C-peptide response by calculating the area under the curve above baseline levels. Two of the children were tested repeatedly. Under the above conditions i.v. glucose and i.v. tolbutamide did not release C-peptide in diabetic children. In contrast, C-peptide secretion during arginine infusion following i.v. glucose or i.v. tolbutamide was significantly enhanced compared to the C-peptide secretion observed during arginine infusion alone. The C-peptide response to oral glucose was sluggish with no effect on the following arginine infusion. The results indicate that during remission in juvenile onset diabetes i.v. glucose and i.v. tolbutamide without themselves being an appropriate signal for C-peptide release amplify the response to a subsequent arginine infusion under appropriate conditions.