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Biomedical subjects

O Mehls

Publications and source records attributed to O Mehls.

At least 163 records · Page 9Linked to original sources
PubMed1991

Recombinant human growth hormone overcomes the growth-suppressive effect of methylprednisolone in uraemic rats.

Paediatric renal allograft recipients frequently manifest growth retardation because of suboptimal graft function and/or concomitant corticosteroid treatment. To determine if the growth-suppressive effects of methylprednisolone (MP) could be counterbalanced by concomitant treatment with recombinant human growth hormone (rhGH) under conditions of normal and reduced renal function, the following animal model was set up. Female uraemic Sprague-Dawley rats (140 g) together with pair-fed and ad libitum-fed control animals were treated with 6 mg/kg per day MP with or without 10 IU/kg per day rhGH. MP suppressed linear growth and weight gain by 43% and 63%, respectively in ad libitum-fed normal control animals; the suppression was more pronounced in uraemic animals (57% and 107%, respectively). The suppressive effects were independent of food intake. The food conversion ratio (weight gain/food intake) was diminished to one-third in control and to more than one-tenth in uraemic animals. Concomitant treatment with rhGH completely reversed the suppression of length gain and weight gain (total body and muscle) and normalized the food conversion ratio. We concluded that rhGH can completely reverse the catabolic effects of corticosteroids under conditions of normal or reduced renal function. The data provide a reasonable rationale for prospective controlled studies on the use of rhGH treatment in paediatric kidney transplant recipients with growth failure.

Animals↗
PubMed1991

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↗
PubMed1991

Growth hormone prevents steroid-induced growth depression in health and uremia.

Treatment with supraphysiological doses of corticosteroids results in protein wasting and impairment of growth, whereas exogenous growth hormone (GH) causes anabolism and improvement of growth. We wanted to know whether the growth depressing effects of methylprednisolone (MP) are more expressed in an organism which is chronically diseased and whether these effects can be counterbalanced by concomitant treatment with recombinant human growth hormone (rhGH). MP in doses from 1 to 9 mg/kg/day caused a dose dependent reduction of length gain, weight gain and weight gain/food intake ratio in 140 g healthy female Sprague-Dawley rats. Food intake was not affected by MP. This points to a change in food metabolism as a mechanism for growth impairment. In addition, treatment with MP inhibited endogenous GH secretion, documented by serum GH concentration profiles over seven hours, decreased IGF-1 serum concentration and disturbed growth cartilage plate architecture. Concomitant treatment with 2.5 to 20 IU/rhGH/kg/day prevented the negative effects of MP on growth in a dose dependent manner and normalized growth plate architecture. In uremic rats in which food efficiency and growth was already reduced, 6 mg MP/kg/day further decreased length gain and prevented weight gain completely by bringing the weight gain/food conversion ratio to the nadir. All effects of MP including reduction of muscle mass could be prevented by concomitant treatment with 10 IU rhGH/kg/day. The effects of MP and rhGH on food efficiency and growth in uremic animals were numerically nearly identical to those in pair fed ad libitum fed controls, but this may be more relevant in the diseased organism in which basal growth is already suppressed.

Animals↗
PubMed1991

Regulation of myocardial isomyosin V1 in uraemic rats.

Cardiac hypertrophy of various aetiologies is consistently associated with increased expression of V3 isomyosin. Uraemia is associated with cardiac hypertrophy. In the present study, we examined regulation of isomyosin in uraemic rats, using gel electrophoresis. Cardiac hypertrophy in uraemic animals was associated with a relative increase in V1 isomyosin. An increased proportion of V1 isomyosin was demonstrable 3 days after subtotal nephrectomy (NX 63.0 +/- 8.8%; control 43.6 +/- 7.2%; P less than 0.01) and persisted during uraemia of 80 days duration. Elevation of V1 isomyosin, relative to pair-fed controls, was observed in uraemic animals of various age. The proportion of V1 isomyosin changed in the same direction as controls when several manouevers were used which changed the isomyosin pattern, but the difference between uraemic animals and controls persisted. We studied the effect of carbohydrate loading or deprivation, starvation or administration of energetically inadequate diets, castration or administration of androgens and sodium depletion. With each of the above interventions, a difference between subtotally nephrectomized animals and sham-operated pair-fed control animals was statistically significant (P less than 0.05). Elevation of V1 isomyosin persisted during combined alpha and beta blockade and was still found when blood pressure was normalized by ACE inhibition using Ramipril. It is concluded that cardiac hypertrophy of uraemia differs from all other forms of cardiac hypertrophy by the occurrence of increased proportion of V1 isomyosin. The proportion of V1 isomyosin responds adequately to regulatory signals but is set at an abnormally high level.

Androgens↗
PubMed1991

Effects of two years of growth hormone treatment in short children with renal disease. The German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

The effect of 1-2 years of growth hormone (GH) treatment (28-30 IU/m2/week) on growth rate, bone age, renal function and metabolic parameters was studied in 61 short, slowly growing children with chronic renal disease (20 with preterminal chronic renal failure (CRF), 24 with end-stage renal failure (ESRF) and 17 with functioning renal transplants). Height velocity (2-year data) significantly increased in children with preterminal CRF from a baseline median of 4.1 cm/year to 9.2 cm/year after 1 year and to 6.6 cm/year after 2 years of treatment. In patients with transplants, the corresponding values were 2.6 cm/year before GH treatment and 8.6 and 7.2 cm/year after 1 and 2 years, respectively. This resulted in normalization of height in 8 of the 16 children who completed 2 years of treatment. The growth response after 1 year in children with preterminal CRF was significantly higher than that in children with ESRF. Bone maturation was in proportion to the increase in chronological age; the expected final height of the children therefore increased by approximately 8-10 cm. In children with preterminal CRF, the decrease in glomerular filtration rate was not affected by 2 years of treatment with GH. The incidence of acute rejection in children with transplants was low; however, a slight stimulatory effect of GH could not be excluded. The major metabolic change induced by exogenous GH was an increase in serum levels of insulin in the three treatment groups, though all glucose tolerance tests remained stable over the 2-year period.

Adolescent↗
PubMed1990

Disturbance of growth hormone--insulin-like growth factor axis in uraemia. Implications for recombinant human growth hormone treatment.

The growth hormone/insulin-like growth factor (IGF) axis is disturbed in uraemia. Elevated plasma growth hormone (GH) levels despite diminished growth suggest GH resistance, which may be due in part to a decreased expression of the growth hormone receptor at the cell membrane. The hepatic production of IGFs under the control of GH is impaired. Furthermore, there is an excess of IGF-binding protein over total IGF as a consequence of reduced renal clearance of low-molecular-weight subunits of the IGF-binding protein (IGF-BP). This results in an absolute (diminished production) and a relative (low bioavailability) deficiency of IGF. Recombinant human growth hormone (rhGH) in doses of 4 IU/m2 per day is able to induce catch-up growth in children with preterminal and terminal renal failure. The growth stimulation of exogenous GH is attributed to its potency to increase the ratio of IGF-I to IGF-BP, followed by a normalization of IGF bioactivity. In renal transplanted children growth is not only disturbed by decreased renal function but also by steroid treatment. Corticosteroids are responsible for catabolism, for suppression of pituitary GH secretion and for inhibition of local production of IGFs. Exogenous rhGH is able to counteract these growth-inhibiting effects. However, it remains to be seen whether long-term GH treatment definitely improves final adult height.

Adolescent↗
PubMed1990

Blood pressure in minimal change and other types of nephrotic syndrome.

Blood pressure was evaluated in adult patients (n = 9) and children (n = 57) with nephrotic syndrome and minimal change glomerulonephritis (GN). Prior to steroid treatment in the edematous phase, hypertension was found in 78% of adults (BP greater than or equal to 140/90 mm Hg or antihypertensive treatment other than diuretics) and 95% of children (BP greater than 95 percentile of age). After complete remission, the prevalence of hypertension decreased to 33% in adults and 19% in children. In 21 children with early focal segmental glomerulosclerosis, the prevalence of hypertension (BP greater than 95th percentile) was 91% and 24% after complete remission. In 20 adult patients with membranous GN, the prevalence of hypertension in the edematous phase was 89% and 30% after complete or partial remission. It is concluded that, irrespective of age, hypertension is a common feature of the nephrotic syndrome unrelated to steroid therapy or renal failure.

Adult↗
PubMed1990

Growth hormone induced rise in glomerular filtration rate is not obliterated by angiotensin-converting enzyme inhibitors.

In 8 healthy normotensive probands with normal glomerular filtration rate, the effect of recombinant human growth hormone (rhGH) on inulin clearance (Cin) was examined in an open study with intraindividual crossover with or without enalapril pretreatment (20 mg/day). rhGH was administered by subcutaneous injection (4.5 U twice daly) for 3 days. On the following day Cin was measured with an enzymatic steady state infusion technique. Systemic hemodynamics and potential metabolic effects of rhGH, i.e., inulin-like growth factors I and II, somatomedin-binding protein, glucagon, C peptide, amino acid pattern, etc., were monitored. On controlled dietary intake of protein, the median Cin rose 72 h after start of rhGh administration from 114 (range 91-158) to 135 (108-167) ml/min/1.73 m2 without enalapril pretreatment (p less than 0.01) and from 111 (88-153) to 131 (100-173 ml/min/1.73 m2 with enalapril pretreatment (p less than 0.02). The results confirm that (1) rhGH increases Cin to a similar extent as extractive GH and (2) further demonstrate that this action is not obliterated by blocking the circulating converting enzyme.

Adult↗
PubMed1989

Low-dose cyclosporin A therapy in cadaver renal transplantation in children.

Fifty-one pediatric patients undergoing a first cadaveric kidney transplantation were followed for at least 2 years after grafting. They were divided into two groups: those treated with methylprednisolone plus azathioprine (AZA) and those treated with methylprednisolone plus low-dose cyclosporin A (CyA; median dose 109 mg/m2 per day = 3.4 mg/kg per day after 1 year). The steroid dosage given was significantly lower in the second group. The 4-year graft survival rate was 68% for the AZA group and 78% for the CyA group. Renal function did not differ significantly in the two groups; after 1, 2, and 3 years, the median 24-h creatinine clearance was 79, 69, and 51 ml/min/1.73 m2, respectively, for the AZA group and 78, 63, and 68 ml/min/1.73 m2, respectively, for the CyA group. Linear growth was similar in the two groups. We conclude that in pediatric patients the results of low-dose CyA immunosuppression do not differ significantly from those obtained with AZA in terms of graft survival, renal function, or growth.

Adolescent↗
PubMed1989

Protein restriction in children with chronic renal failure?

Normal growth can be obtained in infants with congenital renal disease and advanced chronic renal failure by feeding age-corrected amounts of protein and calories. Malnutrition during the first 2 years of life leads to stunting which cannot be corrected later in life. Chronic administration of extra calories has not resulted in catch-up growth. The potential benefit of protein restriction for prevention of renal function has to be balanced against the risk of growth failure in children with chronic renal failure. The problem can only be solved by prospective controlled studies in different age groups.

Age Factors↗
PubMed1989

Vitamin D requirements and vitamin D intoxication in infancy.

Without vitamin D supplementation, the majority of infants seems to be at risk of vitamin D-deficiency rickets. On the other hand, routine vitamin D supplementation of breast-fed infants is not recommended by all authors. In this paper we give an overview of vitamin D metabolism and vitamin D regulation in newborns, which may differ in a certain way from the regulation in adults. Based on this, minimal and optimal requirements for vitamin D in newborns and infants is determined. Furthermore, the paper aims at defining dosages and conditions that are at risk of vitamin D intoxication.

Humans↗
PubMed1989

The acute effect of growth hormone on GFR is obliterated in chronic renal failure.

Recombinant human growth hormone (rhGH) has become available for treatment of growth failure in uremic children. Since GH raises the glomerular filtration rate (GFR) in healthy individuals, there has been concern that treatment with rhGH, by its action on glomerular hemodynamics, may adversely affect the progression of renal failure. To further address this issue, inulin clearance (enzymatic steady-state infusion technique) was measured in 7 healthy normotensive adult volunteers and 7 patients with chronic renal failure from glomerular or non-glomerular causes. Subjects were given 4.5 U bid of rhGH by s.c. injection for 3 days. In volunteers, a significant increase in Cin was noted 72 h after start of rhGH administration from 120 ml/min/1.73 m2 (range 91-158) to 133 (108-167) (p less than 0.02). In contrast, no significant increase in Cin was noted in patients with chronic renal failure (baseline Cin 21 ml/min/1.73 m2, 15-32; after rhGH 22 ml/min/1.73 m2, 15-32) despite pronounced effects of GH on S-cholesterol and urea excretion rate. The results show that stimulation of GFR by short-term administration of rhGH is obliterated in chronic renal failure.

Adult↗
PubMed1989

Improvement of uremic growth failure by recombinant human growth hormone.

Nine stunted prepubertal children with end-stage renal failure were treated by rhGH in supraphysiological doses (4 U/m2/day s.c.) for a period of six to nine months. The six-month data from these children indicated that exogenous rhGH significantly improved the growth rate in all children (mean height velocity SDS before therapy, -2.8; during the treatment period, +2.5). This effect was accompanied by a significant increase in serum somatomedin bioactivity. Low normal basal serum IGF I concentrations were increased by rhGH. Elevated basal serum IGF II concentrations were further increased by rhGH treatment. The pharmacokinetic profile of rhGH in uremia resembles that of the non-uremic state; no accumulation was seen after 14 days of treatment. Glucose tolerance did not change, and insulin levels remained stable throughout the six-month observation period. No rhGH antibodies were detected. Although these short-term results are very encouraging, the effects of rhGH on the prognosis for final height need to be assessed over a longer period of time.

Child↗
PubMed1989

[Kidney involvement in autoimmune diseases].

New aspects of pathogenesis, diagnosis and treatment of renal involvement in classic generalized immune diseases are reported. In Good-pasture's syndrome survival is now possible with high-dose corticosteroids, cyclophosphamide pulse therapy and plasmapheresis. Renal transplantation can be performed with no recurrence of disease once the production of autoantibodies against basal membranes has stopped. Patients with Wegener's disease die if adequate treatment is not provided. Long-term cyclophosphamide therapy can induce complete remission. A solid-phase radioimmunoassay for detection of circulating autoantibodies to neutrophilic cytoplasmic antigens is helpful in the diagnosis and monitoring of therapy. In systemic lupus erythematosus, renal biopsy is only mandatory to solve the question as to whether high-dose steroid treatment should be prescribed: only in the case of diffuse proliferative glomerulonephritis will corticosteroids be beneficial. Intermittent pulse therapy with cyclophosphamide seems to slow down the progression of renal failure, whereas a positive effect of plasmapheresis has not been proven. Cyclosporin A reduces the dosage of corticosteroids needed.

Autoantibodies↗