Eberhard Kauf

Advanced glycation end products in children with chronic renal failure and type 1 diabetes

Abstract Serum levels of advanced glycation end products (AGEs) are markedly elevated in adults with chronic renal failure (CRF) and diabetes mellitus. Accumulation of AGEs in tissues contributes to the development of long-term complications. Up to now little has been known about the formation of AGEs in childhood. We determined serum levels of the well known AGEs pentosidine and Nɛ-carboxymethyllysine (CML) in children with CRF (n=12), end-stage renal disease (ESRD) (n=9), renal transplantation (n=12), and type 1 diabetes mellitus (n=42) and in healthy children (n=20). Pentosidine was measured by high-performance liquid chromatography (HPLC), CML by a competitive enzyme-linked immunosorbent assay (ELISA) system. Serum levels of pentosidine and CML were significantly higher in the children with CRF and ESRD than in controls (P<0.001), but nearly within the normal range after transplantation. Both AGEs showed a significant negative correlation with creatinine clearance (P<0.001). During a single session of low-flux hemodialysis, total pentosidine and CML levels did not change. Free pentosidine, however, was reduced by 78% (P=0.04). Diabe-tic children showed significantly elevated pentosidine levels (P<0.001) despite normal renal function. We conclude that, similar to adults, increased formation and accumulation of AGEs also exist in children with CRF and type 1 diabetes mellitus. At present the best prevention of AGE-related complications is an early renal transplantation in children with ESRD, as well as a careful metabolic monitoring of diabetics.

Sodium selenite therapy and thyroid-hormone status in cystic fibrosis and congenital hypothyroidism.

The effectiveness of a peroral sodium selenite therapy (115 μg Se/m2 BSA/d) administered to cystic fibrosis patients (n=32) could after three months be identified in a significant serum selenium increase (0.69→0.96 μmol/L), a significant malondialdehyde decrease (2.72→1.64 μmol/L), as well as in a significant serum vitamin E increase (4.31→5.72 μg/mL) Parallel to that, a serum T3 increase as well as a highly significant decrease in the serum T4/T3-ratio were found, too, which point to improved peripheral T4→T3 conversion during selenium medication. Type-I-iodothyronine-5′-deiodinase has recently been identified as a specific selenoenzyme.In the case of congenital hypothyroidism (n=37) application of sodium selenite in the above specified dosage yielded a mean serum selenium increase (0.87→1.12 μmol/L), a not significant T3 increase (2.57→2.61 nmol/L) as well as a not significant TSH decrease (5.34→4.49 mIU/L) without an expected T4 decrease. With the serum lipids, however, a lowering of total cholesterol (4.85→4.53 mmol/L) simultaneous with a mean increase in HDL-cholesterol (1.52→1.66 mmol/L) as well as a decrease in LDL-cholesterol (2.93→2.52) could be observed. We view the reduction of the atherogenic serum lipid constellation in the course of selenium medication as an expression of increased thyroid-hormone efficacy.Apart from an improvement of the antioxidant status a stimulation of thyroid-hormone efficacy owing to increased T4→T3 conversion is also noteworthy in sodium selenite medication.

Expression of components of the IGF axis in childhood acute myelogenous leukemia.

Insulin‐like growth factor (IGF) system as regulator for cellular proliferation is of particular interest in search for new prognostic approaches in cancer treatment.

Does Insulin-Like Growth Factor 1 Contribute in Red Blood Cell Transfusions to the Pathogenesis of Retinopathy of Prematurity during Retinal Neovascularization?

Background: Red blood cell (RBC) transfusions are associated with the development of retinopathy of prematurity (ROP). During the period of retinal neovascularization a rise of insulin-like growth factor 1 (IGF-1) may trigger rapid growth of new blood vessels. Objectives: To study endocrine factors in RBC transfusions that might be of importance for ROP. Methods: IGF-1, IGF-2 and their binding proteins 1–3 (IGFBP-1–3) were determined by radioimmunoassays in 7 very-low-birthweight (VLBW) infants with ROP ≧ stage 2 receiving a RBC transfusion, in 10 controls (VLBW infants with ROP ≤ stage 1, no transfusion), in supernatants of 7 RBCs and of 5 washed RBCs (WRBC). Results: IGF-1 (mean ± SD) in infants with ROP was 20.0 ± 4.2 µg/l, in controls 35.9 ± 15.2 µg/l (Mann-Whitney U test, p = 0.030). IGF-1 in RBC was 12.88 ± 5.03 µg/l and in WRBC 0.45 ± 0.74 µg/l (average of the three-course washing procedure). IGF-2 in infants with ROP was 485.67 ± 158.73 µg/l, in controls 389.9 ± 102.8 µg/l (not significant), in RBC 109.50 ± 117.89 µg/l, in WRBC 61.07 ± 30.0 µg/l. Except for IGFBP-3 other IGFBPs were barely or not detectable in RBC or WRBC. Conclusions: Considering lower IGF-1 concentrations in preterm infants than in adults (factor 20), the IGF-1 in RBC transfusions is equivalent to a single dose of 1 µg/kg IGF-1 (5–10% of the adult dose with proved metabolic responses). Endocrinological relationships between the donor’s load and the acceptor’s individual features are a new aspect of potential side effects of RBC transfusions. Further research is necessary to clarify the share of the described IGF administration on the development of ROP.

Associations between ghrelin levels in serum of preterm infants and enteral nutritional state during the first 6 months after birth.

Background  Previous studies have suggested a possible influence of ghrelin on foetal growth. After birth, the regulation of this newly discovered orexigenic peptide is largely unknown.

Blutselengehalte nach Konditionierung sowie im Verlauf der Knochenmarktransplantation bei Kindern mit malignen Erkrankungen

Summary□Patients and Results: Prior to bone marrow transplantation (BMT), at the end of the conditioning phase, we found in 42 investigated children with malignant diseases subnormal lowered plasma- and blood selenium levels. Parallel to the diminished selenium status the plasma glutathione peroxidase activity (Gpx) was not reduced as it is in selenium deficiency, but markedly elevated and probably reflecting cytolytic processes. In the group of combined conditioning (fractionated total body irradiation plus chemotherapy) we found significantly more elevated plasma Gpx values in comparison to the only-chemotherapy group. The renal selenium excretion was elevated during the whole observation and could be caused by disturbed tubular function.□ Conclusion: We conclude, that in the situation of BMT a selenium substitution in a dosage of at least 1 to 2 µg Se/kg/d is necessary. Patients’ selenium status should be monitored by analyses of plasma-and blood selenium contents.

Selen bei Phenylketonuriepatienten

PATIENTS AND METHOD 17 patients (8 female, 9 male; age 8.2 +/- 3.7 years) with phenylketonuria under phenylalanin restricted diet were investigated prior to and after 3 months of selenium substitution (sodium selenite, 115 micrograms Se/m2 BSA/d). Different parameters in blood were determined: selenium, glutathione peroxidase (Gpx) activity, thyroid hormones, blood cell count, lymphocytic antigen expression, muscle function and -enzymes, cardiac ultrasound. RESULTS The main significant results of selenium substitution are: increased plasma-selenium, blood cell selenium, plasma-Gpx activity and left ventricular cardiac index as well as decreased plasma thyroxin, free thyroxin, reverse triiodthyronin, total cholesterol, mean erythrocyte and thrombocyte volume and lymphocytic CD2 expression. CONCLUSION The data indicate metabolic and functional signs of selenium deficiency in patients with phenylketonuria without selenium substitution. We conclude that, despite of lacking clinical symptoms, a selenium supply in phenylketonuria patients under diet is necessary and should be performed with usefull peroral sodium selenite (115 micrograms Se/m2 BSA/d) initially, followed by a dosage between 30 and 60 micrograms Se/m2 BSA/d).Summary□Patients and Method: 17 patients (8 female, 9 male; age 8.2±3.7 years) with phenylketonuria under phenylalanin restricted diet were investigated prior to and after 3 months of selenium substitution (sodium selenite, 115 µg Se/m2 BSA/d). Different parameters in blood were determined: selenium, glutathione peroxidase (Gpx) activity, thyroid hormones, blood cell count, lymphocytic antigen expression, muscle function and -enzymes, cardiac ultrasound.□Results: The main significant results of selenium substitution are: increased plasma-selenium, blood cell selenium, plasma-Gpx activity and left ventricular cardiac index as well as decreased plasma thyroxin, free thyroxin, reverse triiodthyronin, total cholesterol, mean erythrocyte and thrombocyte volume and lymphocytic CD2 expression.□Conclusion: The data indicate metabolic and functional signs of selenium deficiency in patients with phenylketonuria without selenium substitution. We conclude that, despite of lacking clinical symptoms, a selenium supply in phenylketonuria patients under diet is necessary and should be performed with usefull peroral sodium selenite (115 µg Se/m2 BSA/d) initially, followed by a dosage between 30 and 60 µg Se/m2 BSA/d).

X-linked forms of chondrodysplasia punctata: Re-description of two cases originally reported by Professor Erich Hässler in 1940 and the knowledge six decades later

Six decades ago, Professor Erich Hassler, one of the oldest still living European pediatricians who celebrated his 103 t h birthday in April 2002, described two patients with chondrodysplasia punctata. He performed profound clinical, radiological and histological studies of a female neonate with severe X-chromosomal dominant chondrodysplasia punctata type Conradi-Hunermann and investigated an 8-year-old male with a probably X-linked recessive form of chondrodysplasia punctata. He compared these patients with 7 previously described cases also accompanied by stippled epiphyses. To honor the personality of Professor Hassler, both cases were repeated again with his consent. These case reports are connected with the recent knowledge about the molecular background of chondrodysplasia punctata. The X-linked types of chondrodysplasia have been distinguished from other diseases also characterized by stippled epiphyses.

Klinik, Radiologie, Genetik und Therapie hereditärer Skeletterkrankungen Ein historischer Überblick anläßlich des 100. Geburtstages von Professor Erich Häßler

In diesem Beitrag werden klinische Symptomatik, Radiologie, Genetik und die Therapie spezieller Skeletterkrankungen, soweit möglich unter Bezugnahme auf eigene Patienten, diskutiert. Ausgewählt sind hier die Mucopolysaccharidose Typ I-S (Scheie-Syndrom), das Okzipitalhorn-Syndrom und die autosomal-rezessiv erbliche Osteopetrose. Die Arbeit ist Herrn Professor Erich Häßler gewidmet, der 1999 seinen 100.Geburtstag beging. Professor Häßler war von 1953 bis 1965 Direktor der Jenaer Kinderklinik und beschäftigte sich wissenschaftlich mit verschiedenen Knochenerkrankungen wie der Osteopetrose, der Chondrodysplasia punctata und der Mucopolysaccharidose I-H (Hurler- Syndrom).