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Biomedical subjects

G Klaus

Publications and source records attributed to G Klaus.

At least 55 records · Page 3Linked to original sources

Higher KT/V urea associated with greater protein catabolic rate and dietary protein intake in children treated with CCPD compared to CAPD. Mid-European Pediatric CPD Study Group (MPCS).

Being more suitable to children's lifestyle habits, continuous cycling peritoneal dialysis (CCPD) is becoming the treatment modality of first choice in the pediatric CPD population. In order to establish whether these regimens, prescribed on an empirical basis, provide an equally effective dialysis as does standard continuous ambulatory peritoneal dialysis (CAPD), we performed a cross-sectional analysis of dialysate and residual renal small molecule clearances in 85 children aged 3 months to 20 years, who were treated in 16 pediatric dialysis centers. Forty-three children were on CAPD and 42 were on CCPD. The two patient groups did not differ in age, body size, duration of dialysis, underlying disease distribution, or residual renal function. The CAPD patients achieved an average daily drain volume of 159 +/- 40 mL/kg body weight, as compared to 208 +/- 95 mL/kg in the CCPD group (p < 0.005). Average serum creatinine and BUN values were similar in both groups. While the (total) creatinine clearance did not differ, the KT/V urea was significantly higher in the patients treated with CCPD (0.35 +/- 0.12 vs 0.28 +/- 0.13, p < 0.05). The estimated protein catabolic rate (PCR) was significantly higher in the CCPD group (1.39 +/- 0.6 g/kg d) than in the CAPD patients (1.08 +/- 0.48 g/kg d, p < 0.05). Three-day dietary histories, available in 20 patients, showed a similar difference in dietary protein intake between CCPD and CAPD patients. We conclude that CCPD treatment regimens, at the dose currently prescribed in Mid-European pediatric dialysis centers, provide a higher clearance of urea and, possibly, other small molecules.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Chemotherapy with cytosine arabinoside in a child with Burkitt's lymphoma on maintenance hemodialysis and hemofiltration.

A case of Burkitt's lymphoma (stage IV) in an 8-year-old boy with end-stage renal failure due to hemolytic uremic syndrome is reported. The boy was treated by maintenance hemodialysis (HD) and hemofiltration (HF). During chemotherapy treatment with continuous cytosine arabinoside (Ara-C) infusion (100 mg/m2/d) for 7 days, concentrations of Ara-C and its metabolite uracil arabinoside (Ara-U) were measured in blood, dialysate, and filtrate. Ara-C levels were always below 200 ng/ml and were only qualitatively detectable in blood, dialysate, and filtrate. Ara-U levels were higher than 200 ng/ml after 18 h treatment and were measured quantitatively. Ara-U clearance during 3 h HD was 92 ml/min and the calculated mass removal 14.7 mg/3 h. In contrast, the Ara-U clearance during 3 h HF was 14 ml/min and the mass removal was 6.7 mg/3 h. Ara-C and Ara-U are eliminated by HD and HF in anuric patients. A continuous infusion of 100 mg Ara-C m2/d during HD or HF treatment did not result in a serum concentration above 200 ng/ml.

Arabinofuranosyluracil↗

Intermittent and continuous exposure to 1,25(OH)2D3 have different effects on growth plate chondrocytes in vitro.

Intermittent 1,25(OH)2D3 administration is widely used to suppress parathyroid glands in secondary (renal) hyperparathyroidism. It is unknown whether the effects of continuous and intermittent 1,25(OH)2D3 differ on vitamin D target organs other than parathyroids. Using primary cultures of rat chondrocytes (tibia) we compared the effects of continuous versus intermittent exposure to physiologic concentrations of 1 alpha,25(OH)2D3 on proliferation (radiothymidine incorporation), cell count, protein synthesis ([3H]-leucine incorporation), alkaline phosphatase activity (as a marker of differentiation) and 1 alpha,25(OH)2D3 receptor (VDR) regulation. Cells were synchronized and then exposed for variable periods to a medium containing 10% delipidated FCS and 10(-8) M to 10(-12) M 1 alpha,25(OH)2D3 (or 1 beta,25(OH)2D3 as specificity control). Intermittent (8 hr exposure every 48 hr) as well as continuous (sham washing) administration of 1 alpha,25(OH)2D3 had a biphasic effect on proliferation, that is, stimulation at low (10(-12) M) and inhibition at high (10(-8) M) concentrations. At 10(-12) M intermittent 1 alpha,25(OH)2D3 yielded higher cell counts than continuous 1,25(OH)2D3. This was seen in the log phase, which was day 3 (continuous 141 +/- 2.3% of solvent control; intermittent 185 +/- 2.0%) and in the plateau phase of growth, which was day 6 (128 +/- 2.6 vs. 169 +/- 2.7% of solvent control). Dependence on extracellular Ca is suggested by the effects of varying nominal Ca concentrations in the medium and of Ca channel blockers. Even two hours of exposure to 1 alpha,25(OH)2D3 (10(-12) M) yielded maximal activation of AP during postincubation.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗

Effects of rhGH and rhIGF-1 on renal growth and morphology.

It is known that in rodents recombinant human growth hormone (rhGH) and recombinant human insulin-like growth factor (rhIGF-1) increase renal mass. It is uncertain, however, whether renal mass increases in proportion to body growth, or whether renal growth is stimulated selectively. In 120 to 150 g female Sprague-Dawley rats, we measured the effects of rhGH and rhIGF-1 and their combination by the following parameters: kidney weight/body weight ratio, DNA/protein ratio, mRNA of GH receptor and of IGF-1, mitosis index and PCNA (by immunohistology), zonal architecture and glomerular diameter by micromorphometry. Both rhGH and rhIGF-1 dose-dependently increased renal weight and body weight over vehicle treated controls. With rhGH, liver dry weight/body weight ratio increased, but kidney dry weight/body weight ratio remained unchanged (0.99 +/- 0.06 x 10(-3) vs. 1.02 +/- 0.07 in vehicle controls). In contrast, a significant increase of kidney dry weight/body weight ratio was seen in rats treated with rhIGF-1 (1.3 +/- 0.21 x 10(-3). Addition of high doses of rhGH to high doses of rhIGF-1 caused no further increase of the ratio despite a significant further increase of body weight. rhGH increased the abundance of renal GH receptor mRNA (0.46 +/- 0.32 amol/microgram DNA vs. 0.08 +/- 0.07 in controls) and of IGF-1 mRNA (1.35 +/- 0.5 pg/micrograms DNA vs. 0.35 +/- 0.17), whereas no change was seen with IGF-1 treatment. rhGH and rhIGF-1 increased kidney DNA/protein ratio, mitoses and PCNA expression in various renal structures.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Kinetics of serum 1,84 iPTH after high dose of calcitriol in uremic patients.

The temporal relation between oral administration of calcitriol and the nadir of PTH concentration is important for selecting optimal schedules of administration of calcitriol in the treatment of secondary hyperparathyroidism. To further assess this issue we examined 9 patients with preterminal renal failure (3 females, 6 males; median age 58.0 years, range 47-64, median S-Crea 4.8 mg/dl, range 3.7-6.8) with elevated baseline concentrations of 1,84 iPTH (median 46.0 pmol/l, range 18-100). After ingestion of a single oral dose of 2.0 micrograms calcitriol a transient rise in 1,25(OH)2D3 levels was seen with a peak at 6 h (from 20 pg/ml; 14-52 to 43 pg/ml; 35-102). 1,84 iPTH levels did not significantly change in the first 24 h, but were decreased significantly (p 0.01) 48 h after a single oral dose of calcitriol, the time to reach nadir varying from 24 to 96 hours. The percent decrease wa highest in patients with the highest baseline concentrations of 1,84 iPTH. Median 1,84 iPTH levels continued to remain below baseline at 48 h (25.0 pmol/l), 72 h (24.0 pmol/l) and 96 h (24.0 pmol/l) after oral calcitriol. A modest increase of S-Ca was noted which was not statistically significant. We conclude that 1. a single dose of oral calcitriol causes a delayed but long-lasting decrease of 1,84 iPTH, 2. decreased 1,84 iPTH levels persist despite return of calcitriol concentrations to baseline levels and 3. 1,84 iPTH may remain below baseline for more than 96 h.

Calcitriol↗

[Seroepidemiological studies on the detection of Q fever in sheep in middle Thuringia].

In a random samples test altogether 4337 sheep of varying ages from several herds of different sizes in the middle region of Thuringia were investigated with complement fixing test for the existence of Q fever. In 47.1 per cent of the tested herds and in 5 from 8 of the included districts Q fever reagents were provable. The serological detection quota of all tested sheep amounts to 1.11 per cent, but the percentage of serological reagents in mother-sheep was 1.36 per cent, in the female young sheep 1.04 per cent and in the lambs 0.74 per cent. The investigations of rams and sheep for slaughter were negative. Serological testing in 7 sheep showed a Q fever antibody persistence about 6 until 10 months. Increased animal concentration and adverse conditions led to an increase of the Q fever seroprevalence in the herds.

Age Factors↗

Treatment of relapsing peritonitis in pediatric patients on peritoneal dialysis.

Relapsing peritonitis is often due to bacterial colonization of the Tenckhoff catheter and may require removal of the catheter in patients on peritoneal dialysis. The efficacy of a Tenckhoff catheter decontamination procedure was examined in 9 pediatric patients aged 1.5-18 years and compared to the outcome of a historical control group. After repeated dialysate cultures had become negative and cell count was normalized (< 100/ul), intraluminal urokinase (5000 IU/ml) and intraluminal high concentrated antibiotics (vancomycin, fosfomycin, cefotaxim) were instilled sequentially for 3 h and 1 h respectively. This procedure was performed once daily for three days. In addition, the connector was exchanged on the last day. This regimen prevented relapsing peritonitis in all study patients, whereas in the control group in 75.8% of events further relapses occurred, necessitating removal of the Tenckhoff catheter in 7/19 (36.8%) episodes. No side effects of intraluminal urokinase were recorded in any of the patients. We conclude that intraluminal urokinase and intraluminal high concentrated antibiotics combined with connector device exchange are highly effective for prevention of further relapses of peritonitis and reduce the need for Tenckhoff catheter exchange.

Adolescent↗

Effect of vitamin D on growth cartilage cell proliferation in vitro.

Disturbed calcification of the growth plate and stunting is a frequent finding in vitamin D-deficiency rickets, vitamin D-dependency rickets and renal osteodystrophy, illustrating that chondrocytes are a target for vitamin D. This observation prompted an investigation of Ic, 25-dihydroxy vitamin D3 [1,25(OH)2D3] receptor expression and action of vitamin D metabolites on chondrocyte proliferation. In tibial growth plates and in primary cultures of tibial growth cartilage of male Sprague-Dawley rats (80 g) specific binding of [3H]-1,25(OH)2D3 was noted. Scatchard analysis revealed the presence of a single class of non-interacting binding sites. Kd was 10(-11) M irrespective of growth phase. The binding macromolecule had a sedimentation coefficient of 3.5 S. Interaction with DNA was demonstrated by DNA-cellulose affinity chromatography. By immunohistology, growth cartilage cells (rabbit tibia) were shown to express nuclear 1,25(OH)2D3 receptors, most prominently in the proliferative and early hypertrophic zone. This corresponds to binding data which showed highest binding of 1,25(OH)2D3 in the logarithmic growth phase (12,780 molecules/cell versus 4,538 molecules/cell in confluent cells) in primary cultures of growth plate chondrocytes. In the presence of delipidated fetal calf serum 1,25(OH)2D3 had a biphasic effect on cell proliferation and density, i.e. stimulation at 10(-12) M and dose-dependent inhibition at 10(-10) M and below. Inhibition was specific and not seen with 24 (R), 25-dihydroxy-vitamin D3 or dexamethasone. Growth phase-dependent 1,25(OH)2D3 receptor expression and specific effects of 1,25(OH)2D3 on chondrocyte proliferation in vitro point to a role for vitamin D in the homeostasis of growth cartilage of the rat.

Animals↗

1,25(OH)2D3 receptor regulation and 1,25(OH)2D3 effects in primary cultures of growth cartilage cells of the rat.

Vitamin D deficiency leads to disturbed calcification of growth cartilage and enlargement of growth plate, illustrating that chondrocytes are a target for vitamin D. This observation prompted an investigation of 1,25(OH)2D3 receptor expression and action of vitamin D metabolites on chondrocyte proliferation. In primary cultures of tibial growth cartilage of male SD rats (80 g), specific binding of [3H]-1,25(OH)2D3 is noted in both the logarithmic growth phase and at confluence (Nmax 12780 molecules/cell versus 4368 molecules/cell). Scatchard analysis revealed the presence of a single class of noninteracting binding sites. KD was 10(-11) M irrespective of growth phase. The binding macromolecule had a sedimentation coefficient of 3.5 S. Interaction with DNA was demonstrated by DNA cellulose affinity chromatography. In immunohistology, growth cartilage cells (rabbit tibia) expressed nuclear 1,25(OH)2D3 receptors most prominently in the proliferative and hypertrophic zone. This corresponds to binding data which showed highest Nmax in the proliferating cartilage. 1,25(OH)2D3 in the presence of delipidated fetal calf serum (FCS) had a biphasic effect on cell proliferation and density, i.e., stimulation at 10(-12) M and dose-dependent inhibition at 10(-10) M and below. Inhibition was specific and not seen with 24,25(OH)2D3 or dexamethasone. Growth phase-dependent 1,25(OH)2D3 receptor expression and effects of 1,25(OH)2D3 on chondrocyte proliferation point to a role of vitamin D in the homeostasis of growth cartilage.

Alkaline Phosphatase↗

[Prevalence, significance and therapy of premature LH rise and peak in the In Vitro Fertilization program].

The incidence of the premature LH-rise/peak has been analysed in view to the pregnancy rate in 139 HMG and combined Buserelin + HMG cycles of an IVF-ET/GIFT program. A premature LH-rise/peak seems to be correlated with a lower pregnancy rate; therefore the cancellation of the stimulation is recommended in these cases. A gonadotropin suppression by the GnRH-analog Buserelin before and during the HMG treatment proved to be a good method to prevent a premature LH-rise/peak and to decrease the number of cancelled stimulation cycles.

Chorionic Gonadotropin↗

Identification and regulation of 1,25-dihydroxyvitamin D3 receptor activity and biosynthesis of 1,25-dihydroxyvitamin D3. Studies in cultured bovine aortic endothelial cells and human dermal capillaries.

Because 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has been shown to play roles in both proliferation and differentiation of novel target cells, the potential expression of 1,25(OH)2D3 receptor (VDR) activity was investigated in cultured bovine aortic endothelial cells (BAEC). Receptor binding assays performed on nuclear extracts of BAEC revealed a single class of specific, high-affinity VDR that displayed a 4.5-fold increase in maximal ligand binding (Nmax) in rapidly proliferating BAEC compared with confluent, density-arrested cells. When confluent BAEC were incubated with activators of protein kinase C (PKC), Nmax increased 2.5-fold within 6-24 h and this upregulation was prevented by sphingosine, an inhibitor of PKC, as well as by actinomycin D or cycloheximide. Immunohistochemical visualization using a specific MAb disclosed nuclear localized VDR in venular and capillary endothelial cells of human skin biopsies, documenting the expression of VDR, in vivo, and validating the BAEC model. Finally, additional experiments indicated that BAEC formed the 1,25(OH)2D3 hormonal metabolite from 25(OH)D3 substrate, in vitro, and growth curves of BAEC maintained in the presence of 10(-8) M 1,25(OH)2D3 showed a 36% decrease in saturation density. These data provide evidence for the presence of a vitamin D microendocrine system in endothelial cells, consisting of the VDR and a 1 alpha-hydroxylase enzyme capable of producing 1,25(OH)2D3. That both components of this system are coordinately regulated, and that BAEC respond to the 1,25(OH)2D3 hormone by modulating growth kinetics, suggests the existence of a vitamin D autocrine loop in endothelium that may play a role in the development and/or functions of this pathophysiologically significant cell population.

Animals↗

No 1,25-dihydroxyvitamin D3 receptors on osteoclasts of calcium-deficient chicken despite demonstrable receptors on circulating monocytes.

1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is known to stimulate osteoclastic bone resorption in vivo and whole organ bone culture systems in vitro. It has not been established whether 1,25(OH)2D3 acts directly on osteoclasts or whether its action on osteoclasts is mediated via other bone cells (e.g., osteoblasts) or recruitment of osteoclast precursor cells. Circulating monocytes have been characterized as osteoclast precursors. In the present study, vitamin D3-replete chicken on a calcium-deficient diet were studied. Circulating monocytes, whole bone cell preparations, and isolated osteoclasts (differential sedimentation) were examined for presence of 1,25(OH)2D3 receptors. Reversible, specific, and saturable binding of [3H]-1,25(OH)2D3 to a 3.5 S macromolecule was demonstrated in nuclear fractions of monocytes (maximal binding capacity, 48 fmol/mg protein; dissociation constant, 1.3 X 10(-10) M) and of whole bone cell preparations. 1,25(OH)2D3 receptors were not demonstrable in osteoclast preparations (70% pure; detection threshold, 2 fmol/mg protein). Data are consistent with indirect action of 1,25(OH)2D3 on osteoclastic bone resorption.

Animals↗