Urinary excretion of galactosyl-hydroxylysine is a marker of growth in children.

Galactosyl-hydroxylysine (Gal-Hyl) is the predominant product of the posttranslational glycosylation of skeletal collagen. Urinary Gal-Hyl excretion is regarded as a marker of bone resorption in adults, but little information is available on the validity of this parameter in pediatric age groups. Using 24-h urine samples from 88 healthy children and adolescents ages 4-18 yr, reference ranges were established for this age group, and values were compared with measurements in children with overt GH deficiency (n = 14) or Ullrich-Turner syndrome (n = 21). When expressed relative to body weight (Gal-Hyl/wt), urinary Gal-Hyl excretion was 3.2 to 4.7 times higher in subjects 4-16 yr of age than in adults. Highest values were observed in very young children and during the pubertal growth spurt. In the total population, urinary Gal-Hyl/wt was closely related to growth velocity (r = 0.72) and significantly correlated with the urinary excretion of both hydroxyproline (r = 0.74) and deoxypyridinoline (r = 0.88; P < 0.001 each). Urinary Gal-Hyl/wt was significantly lower in children with GH deficiency or Ullrich-Turner syndrome than in healthy children (P < 0.001 each). The urinary excretion of Gal-Hyl was significantly correlated with growth velocity in GH-deficient children (r = 0.69; P = 0.004) but not in patients with Ullrich-Turner syndrome. In the latter, the increase in urinary Gal-Hyl excretion after 3 months of treatment with recombinant human GH correlated significantly with the increase in growth velocity after 12 months of treatment (r = 0.76; P = 0.002). We conclude that the urinary excretion of Gal-Hyl is a valid and potentially useful index of skeletal growth in children.

Taurine metabolism in experimental renal failure.

Taurine is important for the regulation of ionic fluxes in excitable tissues, especially in heart where it is the most abundant amino acid. To investigate a possible role of taurine in uremia, we measured the taurine concentrations in plasma, liver, muscle, heart, and brain tissues of young male Wistar rats. Two groups of rats were studied: (1) rats with acute renal failure (ARF) 12, 24, and 48 hours after bilateral nephrectomy and (2) rats with chronic renal failure (CRF) studied 3 weeks after 5/6 nephrectomy. In ARF animals, taurine increased in plasma and liver two to three times the normal levels, remained unchanged in muscle and brain, but decreased in heart tissue; this decrease (-20%) was significantly correlated with the concomitant increase of BUN and plasma creatinine. In CRF animals, taurine was unchanged in plasma, liver, muscle, and heart, but was increased by 70% in brain accompanied by a high content of gamma-aminoisobutyric acid. The data suggest that in uremia accumulation of taurine is counteracted by increased hepatic elimination and/or decreased synthesis. The depletion of taurine in cardiac muscle might be related to the development of uremic heart disease. The increased concentrations of brain taurine might represent a compensation for the increased neuroexcitability in CRF.

Determination of inorganic plasma sulfate by indirect atomic absorption spectrophotometry.

An indirect method for the determination of inorganic sulfate in small plasma volumes is presented. After removal of protein and phosphate by uranylacetate, sulfate is precipitated by barium chloride. Excess barium in the supernatant is measured by atomic absorption spectrophotometry. The sulfate content of the sample corresponds to the difference of the added and the measured barium. The mean concentration of inorganic plasma sulfate of healthy children, determined by this method, was 0.241 +/- 0.059 mmol/l.

Tissue carnitine concentrations after total parenteral nutrition with and without L-carnitine supplementation.

The concentrations (mumoles/g dry weight) of total carnitine (TC), free carnitine (FC) and acylcarnitine (AC) were determined in skeletal muscle, heart, liver, kidney and brain cortex of male mini pigs (4000-5000 g) after seven days of total parenteral nutrition (TPN) with amino acids 5% (3.0g/kg/d), glucose (25g/kg/d) and lipids 20% (4g/kg/d). This regime was administered with L-carnitine supplementation (1.5 mg/kg/d; n = 7) (group 1) and without it (n = 5) (group 2). Orally alimented animals (n = 5) served as controls (group 3). (Average carnitine intake: 3 mg/d) Carnitine free TPN affected only the concentrations in muscle. TC was markedly reduced (3.6 +/- 0.8) when compared with oral controls (5.8 +/- 0.7) (p<0.01). This decrease was exclusively due to AC, whereas FC concentrations remained almost unchanged. In group 1 the concentrations of TC in skeletal muscle, heart and brain cortex were higher than in both the other groups. The increase was mainly due to AC and FC remained unchanged in heart and brain. The concentrations in liver and kidney were not affected by either carnitine free or carnitine supplemented TPN. AC, determined as described, consists almost entirely of acid soluble acetyl-carnitine, the major product of fatty acid oxidation. Since the AC concentrations were almost exclusively altered by the two TPN-regimes we conclude that the observed changes reflect regulatory changes of fatty acid oxidation. Thus the decrease of muscle TC in group 2 is considered a consequence of an insulin induced down regulation (plasma insulin: mean 20 muU/ml; maximum: 60 muU/ml) of fatty acid oxidation in consequence of high glucose intake (25 g/kg/d). The increased TC concentrations after carnitine supplemented TPN are discussed to reflect an enhancement of oxidative degradation of fatty acids as a pharmacological effect of L-carnitine.

Congenital cystic adenomatoid malformation type 4.

A 9-day-old boy presented in respiratory distress and with failure to thrive. The chest X-ray showed a hyperlucent area of the left lung. A resection of the markedly emphysematous segment 2 of the left upper lobe was performed assuming the emphysematous tissue was due to congenital lobar emphysema (CLE). Histological examination of the lung tissue, however, revealed a pattern consistent with congenital cystic adenomatoid malformation (CCAM) type 4. The therapy for CLE as well as for CCAM is similar, i.e., resection of the emphysematous tissue. As far as the prognosis is concerned, it is important to diagnose the exact type of malformation in order to exclude associated anomalies, as well as the risk of development of malignancies in later life. The frequency of associated malformations of CCAM type 4 is unknown. Although the risk for development of malignancies from CCAM type 4 is not clear at the moment, the possible development of malignancies justifies prompt resection shortly after diagnosis, even in asymptomatic patients. A life-long follow-up in those patients who had a resection of CCAM in early childhood is recommended.

Vitamin D receptor genotypes and changes of bone density in physically active German women with high calcium intake.

Polymorphisms at the vitamin D receptor (VDR) gene have been reported to mediate important differences in bone mineral density (BMD) and bone metabolism. In this longitudinal study we examined the relationships between VDR genotypes and bone metabolism, changes in BMD and changes in ultrasound transmission velocity in a population of healthy unrelated German women. The study population comprised 50 physically active women (aged 43.3 to 62.8 years, 14 premenopausal, 36 postmenopausal) with a daily calcium intake of (mean +/- SD) 1045 +/- 338 mg, who had earlier participated in a longitudinal study on the association of physical activity and bone density and bone turnover. Each participant was genotyped for the BsmI polymorphism at the VDR gene locus. Markers of bone turnover (alkaline phosphatase, osteocalcin, procollagen type I C-terminal propeptide, collagen type I C-terminal telopeptide, tartrate-resistant acid phosphatase) were measured at baseline. BMD (determined by peripheral quantitative computed tomography at the distal radius) and ultrasound transmission velocity through bone (at calcaneus, patella and thumb) were analysed at baseline and 15 months later. The genotypic groups did not differ significantly (p > 0.05) in any of the parameters determined at baseline. Neither were there any differences between these groups in the changes of BMD or ultrasound transmission velocity during the study period. Thus, we conclude that in physically active German women with a relatively high calcium intake the impact of VDR genotypic polymorphisms on bone density, bone metabolism and changes in bone density may be of limited importance.

Plasma inorganic sulfate in children with chronic renal failure.

Plasma sulfate concentration (SO4) was determined in 38 non-dialyzed children with chronic kidney disease and compared to inulin clearance and to other parameters of renal function. SO4 was measured by atomic absorption spectrophotometry. Plasma SO4 was inversely correlated with GFR and effective renal plasma flow. Positive correlations were found between plasma SO4, BUN, serum creatinine and serum phosphate levels. The highest levels of plasma SO4 were observed in 15 children undergoing regular dialysis. It is suggested that sulfate retention might be involved in the pathogenesis of uremic acidosis and bone disease.

A 12-year-old boy with fatal hemolytic-uremic-syndrome, excessive neutrophilia and elevated endogenous granulocyte-colony-stimulating-factor serum concentrations.

We report the case of a 12-year-old boy with fatal enteropathic hemolytic-uremic syndrome who developed excessive neutrophilia in the course of his disease, his leukocyte count exceeding 200,000/mm3. Neutrophilia, as it was observed in this case, is an extreme manifestation of a phenomenon, that is commonly observed in hemolytic-uremic syndrome [Salzmann et al. 1991]. Neutrophilia is suspected to be correlated with a bad prognosis [Walters et al. 1989], but further explanation of this phenomenon is needed. Other underlying diseases related with neutrophilia, especially hematologic malignancies, could be ruled out by far. We examined endogenous G-CSF serum concentrations of the HUS patient from day 6 to 13 in the course of the disease. The assayed concentrations were found to be elevated in the first two samples taken (peak level 340 pg/ml). In the samples taken after plasmapheresis had started, G-CSF concentrations were not found to be elevated. The peak of neutrophilia was reached short before death on day 13 of the disease. We also measured the serum G-CSF concentrations of 28 children aged 3 months to 12 years, who were treated with various infectious and noninfectious diseases in our hospital. In none of the examined samples was there a G-CSF serum concentration exceeding 50 pg/ml. The reported case shows evidence that the commonly observed coincidence of leukocytosis and HUS may reflect the role of G-CSF (and other cytokines) in the inflammatory process underlying the HUS.

Taurine reduces experimental liver injury after cold ischemic preservation and a period of rewarming prior to reperfusion.

Livers of male Wistar rats (250-300 g) were isolated and flushed with 10 ml of Ringer's solution and 10 ml of UW preservation solution. Then the organs were stored for 24 h at 4 degrees C in UW solution. Livers of Group 1 were rinsed with 10 ml of Ringer's solution and reperfused after hypothermic storage with oxygenated Krebs-Henseleit solution (95% O2; 5% CO2) in a nonrecirculating system at constant pressure (10 mmHg) and 37 degrees C. Livers of Group 2 were incubated for 30 min at 37 degrees C prior to reperfusion, in order to simulate rewarming of the organ upon surgical implantation. Livers of Group 3 were treated like Group 2, but taurine was admixed to the UW solution (1 mM). Livers of Group 1 showed little signs of a preservation/reperfusion injury, with low enzyme activities of the parenchymal ALT and endothelial purine nucleoside phosphorylase (PNP) in the postischemic rinse solution (ALT: 19.9 +/- 12.4; PNP: 3.3 +/- 0.4 U/liter), adequate portal flow values about 3 ml/g/min and high O2 uptake at the end of the experiment (VO2: 3.2 +/- 0.4 ml/100g/min). Livers of Group 2 exhibited nearly tenfold higher enzyme activities in the rinse solution (ALT: 247.0 +/- 94.7*; PNP: 29.5 +/- 17.0* U/l) and disturbed tissue perfusion with significantly reduced flow values of about 2 ml/g/min during the first 10 min of reperfusion. As a result, the recovery of O2 uptake was only 2.2 +/- 0.3 ml/100 g/min*. Addition of taurine (Group 3) resulted in a significant reduction of the enzyme loss (ALT: 96.2 +/- 50.0#; PNP:12.4 +/- 7.0# U/liter) and improved portal flow values and O2 uptake at the end of reperfusion (2.7 +/- 0.3 ml/100 g/min#). The results give evidence for the importance of the rewarming period after hypothermic storage, which is inevitable during implantation of the organ in vivo. Taurine seems to exert a protective effect, affecting both the vascular endothelium and parenchymal tissue (*p < 0.05 vs Group 1; # p < 0.05 vs Group 2).

Long-lasting hypoxic preservation of porcine kidney cells. Beneficial effect of taurine on viability and metabolism in a simplified transplantation model.

Taurine administered during hypoxia reduced the cell damage due to O2 deficiency markedly. The beneficial effect outlasted the period of reoxygenation. The mechanisms for the improved survival rates are postulated in a reduced osmoregulatory disturbance of cellular integrity, improved Ca2+ homeostasis and induction of accelerated cellular growth processes. We conclude that taurine supplementation of the conventionally used kidney preservation solution (UW) improves this "gold standard" kidney preservation solution markedly.

Protective effect of taurine on hypoxia and reoxygenation-induced damage of human colon cells (HT 29).

In this experimental model, taurine administered during hypoxia markedly reduced the cell damage due to O2 deficiency, and the beneficial effect outlasted the period of reoxygenation. The mechanisms for the improved survival rates are postulated to be a reduced osmoregulatory disturbance of cellular integrity, improved Ca2+ homeostasis and induction of accelerated cellular growth processes. In our simplified cell culture model the UW solution seems to be the most appropriate solution for the cold (hypoxic) preservation of human colon cells. We conclude, that within this experimental model and under these experimental conditions, taurine supplementation of the conventionally used preservation solutions improved the solutions markedly. Considering our previous studies, taurine seems to be a potent endogenous protective agent against cellular deterioration due to hypoxia and reoxygenation.

The mechanisms of taurine mediated protection against cell damage induced by hypoxia and reoxygenation.

Taurine administered during hypoxia markedly reduced the cell damage due to O2 deficiency and reoxygenation. Different mechanisms are responsible for the improved survival of the renal cell cultures. Taurine markedly reduces the osmoregulatory deterioration during hypoxia and reoxygenation. Calcium homeostasis was markedly improved. Ca2+ efflux during hypoxia as well as Ca2+ overload during reoxygenation was significantly reduced by the amino acid. The effect of taurine was partly comparable to the effect induced by Ca2+ channel blockers. One of the effects mainly responsible for cellular protection seems to be the taurine-induced acceleration of cellular growth processes in spite of hypoxia and reoxygenation. The spectrum of cytoprotective effects of taurine predisposes this substance to be a physiological protective agent responsible for cellular homeostasis or enantiostasis.

Protecting effect of taurine against hypoxic cell damage in renal tubular cells cultured in different transplant preservation solutions.

We conclude that, within this experimental model and under these experimental conditions, taurine supplementation of standard kidney preservation solutions improves survival of kidney cells during hypoxic preservation. The protective effect depends on the taurine concentration, the hypoxic preservation time and the used preservation solution. Physiological taurine concentrations are effective during short hypoxic periods, whereas pharmacological taurine concentrations seem to be needed for longer periods of hypoxia. Within this experimental model University of Wisconsin solution seems to be more effective than Euro collins solution.

[Chronic renal failure in childhood]. / Chronische Niereninsuffizienz im Kindesalter.

Chronic renal failure is rare in children. About one child per year per million population reaches terminal renal insufficiency. The breakdown of the excretory and incretory renal function leads to a damage of nearly all organ systems. Growth retardation and renal osteodystrophy are the most important manifestations in childhood. In the predialytic stage, therapy consists in a low protein, high caloric diet with calcium and vitamin D supplementation as well as the parenteral application of erythropoetin and growth hormone. In terminal renal failure, artificial kidney support is necessary either as hemodialysis or peritoneal dialysis. The ultimate aim is a successful transplantation for full rehabilitation. The multiple medical and psychological problems need a good cooperation between family physician and the center of pediatric nephrology.

[Starvation due to child neglect. Case report and aspects of expert testimony]. / Verhungern infolge Kindesvernachlässigung. Kasuistik und gutachterliche Aspekte.

Case report on 2,5 years old monozygotic twins who died of starvation due to negligence. Different gradings of protein-energy-malnutrition are discussed, among them the Waterlow-classification of PEM. The advantage of the Waterlow-classification is that stunting and wasting can be distinguished. The Waterlow-classification is suitable also for the classification of fatal cases of starvation in childhood. Practical experiences with own cases and cases from the literature are presented.

[Personality and rehabilitation in young adults with renal replacement therapy]. / Persönlichkeitsstruktur und Rehabilitation bei jungen Erwachsenen mit Nierenersatztherapie.

To evaluate the personality structure of young adults treated with renal replacement therapy (RRT) since childhood, we studied 36 patients who had commenced RRT before age 18. At the time of investigation 17 patients were dialyzed and 13 had a functioning renal transplant. Of the dialysis patients, 7 had been transplanted previously. These patients were compared to 26 young adults (minimum age 16) with diabetes mellitus type I (DM) of comparable duration. We used the FP1 test (half-form R; 138 items) by J. Fahrenberg to evaluate personality structure in patients and controls. The results show in general very little difference compared to published normal values and only slight differences between the groups studied. However, there was a trend for RRT patients to feel more aggressive and inhibited than patients with DM. Transplanted patients tended to feel more worried about health problems, while hemodialysis patients felt more self-assured than DM patients. Although it is difficult to assess the psychological burdens of chronic illness and the influence of continuing psychosocial support, it seems remarkable that a better than expected psychiatric adjustment has also been reported in other studies of patients with RRT. In conclusion, adult patients with RRT since childhood have a favorable personality profile as measured by self-evaluation with the FP1-R test, inspite of the well-known multiple medical and social handicaps of this patient population.