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Biomedical subjects

O Mehls

Publications and source records attributed to O Mehls.

At least 127 records · Page 7Linked to original sources
PubMed1994

Synergistic effects of parathyroid hormone and 1,25-dihydroxyvitamin D3 on proliferation and vitamin D receptor expression of rat growth cartilage cells.

We investigated possible interaction of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and PTH on: 1) proliferation (monolayer culture) and colony formation (agarose stabilized suspension cultures); 2) expression of 1,25-(OH)2D3 receptor (VDR); and 3) cAMP response to PTH, using primary cultures of chondrocytes from rat tibia proximal epiphysis. 1 alpha,25-(OH)2D3 stereospecifically stimulated DNA synthesis, cell counts, and colony formation at low concentration (10(-12) M). Within 6 h bovine PTH (bPTH)(1-34), human PTH (hPTH)(28-48) (10(-10) M), (Bu)2cAMP (1-2 mM), and 12-O-tetradecanoyl-13-acetate (10(-8) M) increased [3H]thymidine incorporation in the absence and presence of 1,25-(OH)2D3. Both PTH fragments also stimulated chondrocyte growth and colony formation in a Ca-dependent fashion. Prolonged exposure to bPTH(1-34) or hPTH(28-48) did not affect baseline DNA synthesis but increased the stimulatory effect of 1,25-(OH)2D3. This increase was inhibited in the presence of H7 (inhibition of PKC) or the monoclonal hPTH(1-38) antibody A1-70. In subconfluent chondrocyte cultures VDR was up-regulated by bPTH(1-34) and hPTH(28-48) (10(-10) M) or activators of protein kinase C (PKC), but not by (Bu)2cAMP. It was blocked by cycloheximide and actinomycin D and persisted in the presence of Ca-channel blockers. Inhibition of PKC by H7 also blocked the effect of bPTH(1-34) on VDR. The cAMP response to bPTH(1-34) was not affected by 1,25-(OH)2D3. We conclude that: 1) DNA synthesis, cell proliferation, and colony formation in chondrocyte monolayer or suspension cultures is increased by aminoterminal and midregional PTH fragments and by cAMP analogs in a Ca- dependent fashion; 2) bPTH(1-34) and hPTH(28-48) up-regulate VDR by cAMP-independent, PKC-dependent steps requiring transcriptional and translational processes; both PTH fragments also amplify the effect of 1,25-(OH)2D3 on DNA synthesis; and 3) no difference is found between the bPTH(1-34) and hPTH(28-48) fragments with respect to chondrocyte proliferation and VDR up-regulation, although the two differ with respect to stimulation of cAMP production.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

[Kidney transplantation in children].

Renal transplantation has become an established form of therapy for children with endstage renal disease. Evaluation and elimination of potential risk factors, standardization of operative technique and better immunosuppressive regimens improved the outcome in paediatric patients. A shortage or organs means that transplantations cannot always be offered to children for whom it would be the treatment of choice. Kidney donation by living relatives opens up the potential for optimal rehabilitation of patients in the paediatric age group.

Adolescent↗
PubMed1994

Single-dose oral calcitriol and changes of plasma 1,84iPTH in uremic children.

Both intravenous and oral 1,25(OH)2 D3 pulse therapy are effective in decreasing iPTH in patients with chronic renal failure. In order to understand why intermittent application of calcitriol is effective, we investigated 10 children with advanced renal failure (4 female, 6 male; median age 6.5 [3-16] years; body surface area 0.58-1.57m2; CCR 7 [5-47] mL/min/1.73m2) with elevated baseline concentrations of 1,84iPTH (median 63.5 [9.4-300] pmol/L). After a standard dose of 2 micrograms calcitriol per os (equal to 1.27-3.45 micrograms/m2), serum 1,25(OH)2D3 concentrations increased. The peak concentration occurred after 6 h (3-12), and 1,25(OH)2D3 serum levels returned to baseline by 48 h. 1,84iPTH concentrations were significantly suppressed by 6-72 h. The median maximal decrease was 51.4% of baseline (22.3%-74%). The decrement was a function of baseline 1,84iPTH, but not of 1,25(OH)2D3 serum peak concentration, area under the curve, body surface area, or change in ionized serum calcium. We conclude: (i) oral 1,25(OH)2D3 has a prolonged (up to 72 h) suppressive effect on 1,84iPTH concentrations in uremic patients, and (ii) the wide interindividual variation in suppression of 1,84iPTH was not explained by the kinetics of 1,25(OH)2D3 concentration, which implies that additional factors influence the 1,84iPTH response to 1,25(OH)2D3.

Administration, Oral↗
PubMed1994

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↗
PubMed1994

Stimulation of growth by recombinant human growth hormone in children undergoing peritoneal or hemodialysis treatment. German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

Fourteen patients on hemodialysis (HD) and 17 patients on continuous peritoneal dialysis (CPD) were treated with 28-30 IU/m2/week of recombinant human growth hormone (rhGH) for at least 12 months. The HD and CPD patient groups were comparable with regard to age, bone age, height standard deviation scores (SDS), and height velocity at start of treatment. During the first year of rhGH treatment, height velocity increased from 2.9 +/- 1.9 to 5.5 +/- 1.7 cm/year in the HD group and from 3.0 +/- 2.2 to 7.2 +/- 3.2 cm/year in the CPD group. The increase in growth rate was significant in both groups (p < 0.001), and tended to be significantly greater in the CPD than in the HD group (p = 0.09). The marked acceleration of growth under rhGH treatment resulted in an increase in relative height by 0.37 +/- 0.38 SDS in the HD group and by 0.47 +/- 0.69 SDS in the CPD group during the first treatment year. Seven HD and 7 CPD patients completed a second year of rhGH treatment. In these patients, height velocity dropped to 3.6 +/- 2.7 cm/year (HD) and 3.6 +/- 2.3 cm/year (CPD), respectively during the second treatment year. We conclude that rhGH treatment accelerates growth in children both on HD and CPD. The treatment response tends to be greater in CPD compared to HD patients. The efficacy of treatment decreases considerably during the second treatment year.

Adolescent↗
PubMed1993

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↗
PubMed1993

Changing pattern of chronic renal failure and renal replacement therapy in children and adolescents: a 20-year single centre study.

We analysed the demographic data, clinical course and survival on different forms of renal replacement therapy (RRT) of 374 children and adolescents with chronic renal failure observed between 1969 and 1988 and compared the findings for the four subsequent 5-year periods. The proportion of children below 5 years of age rose from 21% to 47%. With time the incidence of glomerulonephritis increased and that of pyelonephritis decreased. As RRT became more common, more very young children and more adolescents were admitted to the study. In the last 5 years continuous ambulatory peritoneal dialysis (CAPD) and haemodialysis (HD) were performed to the same extent as the initial form of RRT. The time a subject had to wait for a first transplant decreased from 36 to 21 months. Between 1969 and 1988 overall survival on any form of RRT increased to 77% after 10 years of therapy. In the last observation period 2-year patient survival was 100% both on HD and CAPD. First cadaver graft survival after 4 years improved from 25% in 1969-1973 to 69% in 1984-1988.

Adolescent↗
PubMed1993

Growth hormone-induced glomerular hyperfiltration is dependent on vasodilating prostanoids.

Exogenous growth hormone (GH) and insulin-like growth factor (IGF)-I induce an increase of renal hemodynamics in normal subjects, but the precise mechanism mediating this phenomenon has not been explored in humans. We investigated whether the renal response to exogenous GH requires the presence of vasodilating prostaglandins (PG). In 10 healthy normotensive women with normal renal function, the effect of recombinant human (rh)GH on glomerular filtration rate (GFR) was examined using an intraindividual cross-over design. The subjects were studied under conditions of normal hydration and controlled sodium and protein intake without and with coadministration of indomethacin, 150 mg/d. rhGH, 4.5 IU twice per day, was administered by subcutaneous self-injection for 3 days. GFR was measured as inulin clearance (Cin) in the morning hours in the fasting state in supine position before and after 3 days of rhGH treatment. Baseline GFR was 115.7 +/- 10.1 (SD) mL/min/1.73 m2. Three days of treatment with rhGH caused a 50% increase in serum IGF-I values and GFR increased by 10% to 127.9 +/- 11.7 mL/min/1.73 m2 (P < 0.03). The study was repeated under coadministration of indomethacin, which was started 2 days before application of rhGH. Despite a similar increase in serum IGF-I values, the increase in GFR was completely blocked by indomethacin. Urinary PGE2 excretion was not stimulated by rhGH, but decreased by 50% during indomethacin treatment, as expected. These findings suggest that the increase of GFR during GH treatment in humans is mediated by or requires the presence of vasodilating prostanoids.

Adult↗
PubMed1993

Efficacy and safety of growth hormone treatment in short children with renal allografts: three year experience. Members of the German Study Group for Growth Hormone Treatment in Children with Renal Allografts.

The majority of children with renal allografts have diminished growth and reduced final height. Impaired allograft function and glucocorticoid treatment are the main contributing factors. Since recombinant human growth hormone (rhGH) treatment was able to counteract the growth depressing effects of glucocorticoids in experimental uremia, an open-labeled prospective study in 17 short children with renal allografts was designed to investigate the efficacy of rhGH therapy (30 IU/m2/week) with special emphasis on the safety regarding graft function and carbohydrate metabolism. Height velocity in prepubertal children (N = 10) increased from baseline median 2.2 cm/year to 7.9 cm/year after one year (P < 0.01), 7.2 cm/year after two years (P < 0.01), and 5.5 cm/year (P < 0.05) after three years of rhGH therapy. This resulted in a normalization of height in three out of seven patients after two years and in three out of five after three years of therapy. Growth stimulation in pubertal children was less consistent. Bone maturation paralleled chronological age. The effect of rhGH treatment on longitudinal growth may be partially attributable to the improved ratio between the serum concentration of the insulin-like growth factor (IGF)-I and its major binding protein (BP) IGFBP-3 leading to a normal IGF bioactivity. The incidence of acute rejection crises in the study group (corrected for time after grafting) did not differ from that of untreated retrospective "controls" (0.10 vs. 0.12 episodes per patient and year). No systematic effect of rhGH on glomerular filtration rate assessed by repeated inulin and creatinine clearances was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

Predictors of growth response to rhGH in short children before and after renal transplantation. German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

Many children with chronic renal failure (CRF) present with a reduced height and a reduced height velocity resulting in diminished final height irrespective of renal replacement therapy. Recombinant human growth hormone (rhGH) has become a new treatment modality for short renal patients, and the response to rhGH varies widely. In order to identify possible predictors of response to rhGH, the influence of sex, chronological age, bone age, pubertal status, height and height velocity at basal, target height, treatment modality for CRF, residual glomerular filtration rate (GFR), and steroid treatment was analyzed by single and multiple regression analysis in 49 children prior to and after renal transplantation. During the first treatment year with 28 to 30 IU rhGH/m2/week given by daily s.c. injections, height velocity was highest in patients on conservative treatment and lowest in patients on dialysis. Height velocity expressed in cm/year was inversely correlated with age (r = -0.63; P < 0.0001) and positively correlated with pretreatment height velocity (r = 0.65; P < 0.0001). The increment in height velocity SDS (chronological age) was significantly negatively correlated with the pretreatment height velocity SDS (chronological age) (r = -0.58, P < 0.001), indicating that at any given age the slowest growing children tended to respond best to rhGH treatment. It is concluded that the response to rhGH is significantly influenced by age, pretreatment height velocity, and treatment modality for CRF, whereas the influence of other variables is less important.

Body Height↗
PubMed1993

Evaluation of protein intake by dietary diaries and urea-N excretion in children with chronic renal failure. European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood.

In 1988 a European multicentre, randomized trial was started in order to analyse the influence of protein intake on the progression of chronic renal failure in children. Compliance to the dietary prescriptions, i.e. protein intake, was checked by written dietary diaries and in addition by urinary urea-N excretion. This provided a unique chance to compare both methods in non-hospitalized children. Of a total of 200 patients 123 were selected, in whom at least 4 consecutive dietary diaries plus 4 completely collected 24-hour urine samples were available. Whereas urea-N excretion and simultaneously recorded protein intake did not correlate well, mean urinary urea-N excretion and mean protein intake of at least 4 observations in each patient correlated highly (r = 0.803, p = 0.0001). The difference between protein-N intake and urea-N excretion was not a constant amount of 0.031 g/kg/day as proposed by Maroni et al. [1985] but figured at 0.085 +/- 0.061 g/kg/day and was highly correlated to protein intake (r = 0.839, p = 0.0001). The correlation of protein intake and urea-N excretion was best described by the formula: protein-intake (g/kg/day) = (urea-N excretion [g/kg/day]x 15.39) -0.8 or protein intake (g/kg/day) = urea-N excretion (g/kg/day) x 9.5. Maroni's formula underestimated the high protein intake of young children. In only a few patients dietary diaries severely underestimated protein intake as compared to calculation by urea-N excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

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↗