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Biomedical subjects

O Mehls

Publications and source records attributed to O Mehls.

At least 145 records · Page 8Linked to original sources
PubMed1992

Growth hormone treatment in children with preterminal chronic renal failure: no adverse effect on glomerular filtration rate.

Impaired growth and stunting remains a major therapeutic problem in children with chronic renal failure (CRF). Recombinant human growth hormone (rhGH) treatment may be beneficial, but concern has been raised about possible side-effects, i.e. deterioration of renal function and glucose intolerance. We have treated 10 prepubertal children with CRF (median age 7.5 [1.7-10.0] years) with 4 IU rhGH/m2 per day s.c. over a period of 1 year. Height velocity increased significantly (P less than 0.03) from basal 4.6 (2.0-14.0) cm/year to 9.7 (6.8-17.6) cm/year. Height velocity SDS for chronological age and for bone age increased in all children from basal median -2.3 to +3.8 (P less than 0.005). Median glomerular filtration rate (GFR) measured by single injection inulin clearance at onset was 18 (11-66) ml/min per 1.73 m2 and did not change significantly during the treatment year. The loss of GFR as estimated by creatinine clearance was similar during the treatment year (median loss 1.3 ml/min per 1.73 m2) compared to the year before treatment (median loss 3.7 ml/min per 1.73 m2). Serum glucose levels during an oral glucose tolerance test did not change, but fasting as well as stimulated insulin levels increased significantly with time during the study period. It is concluded that the rhGH regimen employed was remarkably effective in improving growth velocity in children with CRF without adversely affecting GFR. Glucose homeostasis remained stable, but at the expense of increased serum insulin levels.

Blood Glucose↗
PubMed1992

Lipid levels in monocytes of patients with moderate hyperlipoproteinemia.

Recent studies suggest that circulating blood monocytes may serve as a lipid clearance system in early atherosclerotic lesions. To evaluate the influence of moderate hyperlipoproteinemia on monocyte lipid concentrations, we measured fasting serum and monocyte lipid levels in 7 healthy individuals, in 7 patients with primary hypercholesterolemia and in 17 patients with secondary dyslipidemia due to chronic renal failure; 10 of these patients were treated by hemodialysis (HD) and 7 patients by continuous ambulatory peritoneal dialysis (CAPD). The hypercholesterolemic patients had elevated serum levels of total cholesterol, LDL-cholesterol and apolipoprotein (apo) B, but normal plasma triglycerides. Patients on dialysis had elevated serum levels of triglycerides, serum cholesterol (CAPD only) and VLDL- and LDL-cholesterol (CAPD only) and apo B (CAPD only), whereas HDL-cholesterol and apo A-I levels (HD only) were decreased. In monocytes, we measured the content of free cholesterol (FC), cholesteryl esters (CE) and triglycerides (TG). The normal mean intracellular concentrations of FC, CE and TG were 48.3, 1.7 and 2.4 micrograms/mg cell protein, respectively. All monocyte lipid levels were similar in patients and controls, with the exception of a decreased content of FC (30.8 micrograms/mg) in monocytes of HD patients. We conclude that moderate increases in serum lipoprotein lipid levels are not associated with lipid accumulation in monocytes.

Adolescent↗
PubMed1992

Growth failure in renal disease.

Children with congenital CRF lose height potential mainly during two distinct growth periods; infancy and puberty. The onset of puberty is late, the pubertal growth spurt starts from a very low rate of growth velocity, and peak height velocity is lower than normal although the absolute increment of height velocity is comparable to the increment in normal children. Furthermore, the duration of pubertal growth spurt is reduced in CRF. During infancy and early childhood, malnutrition, electrolyte disturbances and metabolic acidosis are the main contributing factors for reduced growth, whereas hormonal disturbances are responsible for growth impairment during puberty. There is evidence for resistance to growth hormone in CRF, which starts in early childhood and persists until the end of puberty. Growth hormone secretion is normal in CRF, but GH half-life is prolonged. The binding activity of the stable growth hormone binding protein is reduced, which points to a low receptor expression in the liver. Hepatic IGF-I production is diminished. However, the serum concentration of IGF binding proteins (IGFBP) is increased due to reduced renal filtration of low molecular weight subunits of IGFBP. Mainly, the accumulation of IGFBP-3 leads to increased IGF-binding capacity of the uraemic serum. Both, reduced IGF-I production and increased binding of IGF to IGFBP-3 result in decreased IGF bioactivity. During infancy, loss of growth potential can be prevented by adequate nutrition. Later in life, catch-up growth cannot be induced by nutritional intervention or dialysis. Renal transplantation allows catch-up growth in only a small percentage of patients. Treatment with one IU rhGH/kg/week improves growth velocity and growth in all stages of renal disease. The mean increment of height in prepubertal children is +1.5 SDS within two treatment years. The effect of rhGH during puberty as well as the effect on final height remain to be determined.

Adolescent↗
PubMed1992

Growth hormone in renal transplantation--the mode of action, animal studies, and clinical use.

During circulation, growth hormone (GH) is bound to about 50% by the high-affinity, low-capacity GH-binding protein (BP). GHBP represents the extracellular binding domain of the GH receptor and modulates the action of GH. After binding to its receptor, GH induces the local production of insulin-like growth factor 1 (IGF-1) by autocrine and paracrine mechanisms. In uremia, the plasma GH-binding activity is low and does not get up-regulated by recombinant human GH treatment, which is in contrast to the experience in short, normal children. There is evidence that hepatic IGF-1 production is low, whereas the serum concentration of IGF-binding protein 3 (IGF-BP3) and other IGFBPs is increased because of the reduced renal clearance of the low-molecular-weight fragment of IGF-BP. This result in the reduced bioavailability of free IGF-1 and reduced IGF bioactivity. There is a strong interaction between GH and corticosteroids. Corticosteroids suppress growth by reducing the food efficiency ratio (weight gain per food intake), reduce pituitary GH secretion, and decrease the local production of and cell responsiveness for IGF-1. The growth-depressing and catabolic effects of corticosteroids can be counterbalanced dose dependently by recombinant human GH in animal experiments, and growth can be improved in corticosteroid-treated renal allograft recipients with and without normal renal function. It is not clear at this time to what extent GH may induce acute or chronic rejection crises.

Adrenal Cortex Hormones↗
PubMed1992

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↗
PubMed1992

Evaluation of peritoneal solute transfer by the peritoneal equilibration test in children.

To evaluate the characteristics of peritoneal kinetics in the young, we investigated solute and water transfer rates by a modified Peritoneal Equilibration Test (PET) in 20 pediatric patients aged 1.9 to 19.8 years. 1000 ml/m2 body surface area of a 2.3% glucose PD solution were instilled in the peritoneal cavity. Glucose, creatinine, urea, sodium, potassium and phosphate were measured in the dialysate (D), 7 times during 4 hours and in plasma (P) after 2 hours dwell time. At 4 hours, the mean (+/- SD) D/P ratio was 1.06 +/- 0.16 for urea, 0.79 +/- 0.14 for creatinine, 0.82 +/- 0.21 for potassium, 0.92 +/- 0.04 for sodium and 0.79 +/- 0.30 for phosphate. Mean D/D0 of glucose was 0.36 +/- 0.13. The 4-hour solute equilibration curves were analytically best approximated by logarithmic functions for urea (mean R2 = 0.983), creatinine (R2 = 0.973) and potassium (R2 = 0.979), by a linear function for phosphate (R2 = 0.964), and by an exponential model for glucose (R2 = 0.969). The linear or exponential regression coefficients were used to express the peritoneal solute transfer rates. Although the transfer rates of most solutes were correlated with each other, the individual variation of peritoneal permeability for different solutes was high. Close associations were observed between the glucose and creatinine transfer rates (r = 0.91, p < 0.0001) and between ultrafiltration rate and glucose (r = -0.90, p < 0.0005) and creatinine (r = -0.88, p < 0.005). Peritoneal permeability for all solutes tended to be inversely correlated with body size (urea transfer rate vs. height: r = 0.49, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

New insights into endocrine disturbances of chronic renal failure.

Secondary hyperparathyroidism occurs in the very early stages of renal failure. In the past, there has been considerable controversy concerning the signal triggering secondary hyperparathyroidism. Recently, it has become clear that secondary hyperparathyroidism is, at least to a major extent, the consequence of the deranged endocrine feedback between calcitriol, the secretory product of renal 1-alpha-hydroxylase, and parathyroid hormone. Another recent insight concerns disturbances of the secretion of hypophyseal hormones. These hormones, e.g. GH, gonadotropins and TSH, are secreted in a pulsatile fashion. For all three hormones, reversible abnormalities of secretory rhythmicity have been demonstrated in renal failure. Disturbed oscillatory patterns of hormone secretion provide a new dimension to our understanding of the genesis of endocrine disturbances.

Feedback↗
PubMed1992

Multicentre randomized study on the effect of a low-protein diet on the progression of renal failure in childhood: one-year results. European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood.

After an adaptation period of 6 months, 200 children (mean age 10.3 years; 138 boys and 62 girls) were stratified according to their renal diseases and the progression of renal failure during the adaptation period and randomized for low protein intake amounting to the WHO safe levels for age (0.8-1.1 g/kg/day) or free protein intake. Energy intake of both groups should be near the WHO recommendations. Compliance was controlled by written dietary diaries and urea-N excretion. 101 children had been randomized for the diet group and 99 for the control group. 165 of these patients finished their first year after randomization. Mean protein intake was 126% of the recommendations in the diet group vs. 187% in the control group while energy intake was similar in both groups (85 vs. 90%). SDS for height at start and 1 year later did not change (diet: -0.9 vs. -1.1; control: -0.9 vs. -0.9). Weight gain was not different. Only the stratification for two groups according to the progression of renal failure ('nonprogressive' and 'progressive' diseases) was used in the analyses. Progression of renal disease during the adaptation period proved to be a significant prognostic factor. Mean loss of GFR/year was similar in patients with 'nonprogressive' diseases in the control group (-1.1 ml) and the diet group (-1.3 ml). In patients with 'progressive' diseases mean loss of GFR was significantly higher in the diet group (-6.5 ml) than in the control group (-4.0 ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Therapeutic value of recombinant human growth hormone in children with chronic renal failure.

In chronic renal failure (CRF), serum growth hormone (GH) levels are elevated due to a reduced renal metabolic clearance. Although the concentration of circulating GH is increased in CRF, insensitivity to GH is noted. This is mainly due to a decreased production of hepatic insulin-like growth factor (IGF)-I and an accumulation of its binding protein (IGFBP-3), both resulting in a low concentration of free active IGF-I. Treatment with recombinant human (rh) GH in doses of about 30 IU/m2/week, increases the serum concentration of IGF-I, normalizes somatomedin (IGF) bioactivity and leads to catch-up growth. The anabolic effects of rhGH are seen from an increase in muscle mass and a reduction of fat mass. rhGH treatment is also able to compensate for the growth-depressing effects of corticosteroids in animal studies and in children after renal transplantation.

Body Height↗
PubMed1991

How safe is the treatment of uraemic children with recombinant human growth hormone?

Exogenous growth hormone (GH) treatment for growth failure in uraemic children is effective over a period of up to 3 years. The safety of this new treatment modality is remarkably high, at least for this short period of time. Despite a reduced renal metabolic clearance rate of GH in uraemia, exogenous GH does not accumulate in the serum. In a dose range of 28 units/m2 per week, GH does not impair glucose tolerance but increases serum insulin levels, indicating that euglycaemia is maintained at the expense of increased insulin secretion. No alterations of lipid metabolism, mineral metabolism, pituitary-thyroid axis and blood pressure were observed. The GH-induced glomerular hyperfiltration in healthy subjects seems to be obliterated in chronic renal failure. Accordingly, no accelerated progression of renal disease was observed under GH treatment. However, potential side effects during long-term treatment, especially regarding carbohydrate metabolism and malignancy in children under immunosuppression, are not yet excluded.

Child↗
PubMed1991

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↗
PubMed1991

Low-protein diet in children with chronic renal failure--1-year results. European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood.

In 1988 the European Study for Nutritional Treatment of Children with Chronic Renal Failure started its multicentre randomized trial to investigate the influence of protein intake on the progression of renal failure. A total of 284 children had been registered. Of these 221 were accepted for the study. The data from 105 patients after 1 year of study are available for preliminary analysis. Fifty children were randomized for the diet group and 55 for the control group. Both groups were comparable concerning age, glomuerlar filtration rate (GFR) and height standard deviation score for chronological age at the start of the study period and the distribution of primary renal diseases and sex. Limits for protein and energy intake were set according to the safe levels and recommendations given by the World Health Organization. The compliance with dietary prescriptions as calculated from dietary diaries was good. A low-protein diet did not do any harm to the children with respect to length gain and weight gain. The progression of renal failure was minimal in the diet group (mean loss of GFR 3.6 ml/min per 1.73 m2 per year) as well as in the control group (2.3 ml/min per 1.73 m2 per year). The differences between the diet group and the control group were statistically not significant when either all patients or only subgroups of various primary renal diseases were analysed. When only patients with a good compliance were considered (documented by dietary diaries or by urea nitrogen excretion) the same results were obtained. In summary, reduction of protein intake was accepted by the majority of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Influence of growth hormone and insulin-like growth factor-I on kidney function and kidney growth.

Decreased glomerular filtration rate (GFR) in hypopituitarism and increased GFR in acromegaly suggest that growth hormone (GH) has a substantial effect on renal haemodynamics. Extractive and recombinant human (rh) GH in healthy volunteers increased effective renal plasma flow (ERPF) and GFR by 10% and 15% respectively. Renal response to GH was delayed and occurred at the same time as an increase in plasma insulin-like growth factor (IGF)-I values, whereas infusion of rhIGF-I promptly increased GFR and ERPF, indicating that the haemodynamic response of the kidney to GH is mediated by IGF-I. In chronic renal failure (CRF), the acute effect of GH on GFR is obliterated. This might protect the diseased kidney against the undesired consequences of hyperfiltration. Indeed, rhGH treatment for 1 year in children with CRF did not lead to an accelerated decline in GFR compared with the year before treatment. GH and IGF-I also affect renal growth. Exposure to excessive GH in transgenic mice causes renomegaly and progressive glomerular sclerosis. In acromegalic humans, increased renal size and weight and increased glomerular diameter are well known, whereas renal failure is not a long-term hazard. At least in normal and hypophysectomized rats treated with doses comparable with the therapeutic regimens used in stunted children, rhGH increased renal weight but in proportion to the increase in body weight indicating an isometric effect of GH on renal growth. From these data, major renal long-term side effects of rhGH treatment in children with CRF appear unlikely.

Animals↗
PubMed1991

Growth hormone resistance and inhibition of somatomedin activity by excess of insulin-like growth factor binding protein in uraemia.

Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) were studied in children with end-stage renal failure (ESRF, n = 31) and chronic renal failure (n = 11) with residual glomerular filtration. Somatomedin bioactivity in patient sera was found to be decreased while IGF-I and IGF-II levels by radio-immunoassay (RIA) were normal. In contrast, IGFBP-1 and IGFBP-3 levels (measured by RIA) were markedly increased in uraemia. Excess IGFBP was shown to be able to bind IGF by determination of the free IGF binding capacity. Using high-performance liquid chromatography a shift of the IGFBP-3 profile to low molecular weight components could be demonstrated in ESRF. Affinity cross-linking experiments showed that these low molecular weight IGFBP-3 immunoreactive forms are biologically active. In normal urine only IGFBP-3 forms smaller than 60 kDa were detected with a major peak at 12-20 kDa. Removal of excessive IGFBP from patient sera by affinity chromatography on an IGF-II Sepharose column resulted in a significant increase in somatomedin bioactivity. Model calculations on the interaction of IGF and IGFBP using empirical data suggested a reduction of IGF secretion in uraemia by an order of magnitude. It is concluded: (1) that renal failure causes an accumulation of low molecular weight IGFBP, (2) that the resulting excess of IGFBP acts as a somatomedin inhibitor, and (3) that in uraemia there is a relative growth hormone resistance with respect to IGF production.

Adolescent↗
PubMed1991

Plasma growth hormone-binding activity is low in uraemic children.

Plasma growth hormone-binding protein (GH-BP) activity was evaluated in two groups of prepubertal children with chronic renal failure (CRF) who had been treated with recombinant human GH (rhGH). Group 1 consisted of eight children (mean chronological age 10.8 years) with advanced renal failure; group 2 consisted of nine children (mean chronological age 6 years) presenting with end-stage renal disease, who were on dialysis. Before treatment the specific binding of (125I)hGH to high-affinity GH-BP was low in the two groups (group 1, 17.3 +/- 1.6% of radioactivity; group 2, 14.2 +/- 1.4%) compared with the mean value obtained in normal prepubertal children (24.8 +/- 1.7%). No significant changes in GH-BP activity were found during the 1st year of GH therapy, although growth velocity and plasma levels of insulin-like growth factor-I increased significantly in both groups. The low GH-binding activity found in children with CRF supports the state of GH resistance. The reason for the absence of a GH-BP response to GH therapy has to be clarified.

Carrier Proteins↗