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Biomedical subjects

O Mehls

Publications and source records attributed to O Mehls.

At least 91 records · Page 5Linked to original sources
PubMed1996

Bilateral renal venous thrombosis in a neonate associated with resistance to activated protein C.

Renal venous thrombosis (RVT) is a serious complication of neonates. In most cases the underlying cause of RVT remains unclear. Here we report a neonate with bilateral RVT and adrenal haemorrhage associated with a heterozygous mutation of the gene encoding for clotting factor V, resulting in resistance to activated protein C. Vigorous thrombolytic therapy with urokinase followed by recombinant tissue plasminogen activator dissolved the thrombus in the inferior vena cava and restored perfusion of both kidneys. However, a haemorrhagic rupture of the right kidney occurred, requiring emergency nephrectomy. Despite reperfusion of the left kidney and resumption of urine output, the patient remained dialysis dependent. Due to persistent adrenal insufficiency, long-term substitution of hydrocortisone was necessary. The patient was prophylactically treated with coumarin during the first 6 months of life and is now waiting for renal transplant at the age of 1 year.

Anticoagulants↗
PubMed1996

Growth promoting effects of growth hormone and IGF-I are additive in experimental uremia.

Exogenous growth hormone (GH) stimulates the endogenous production of IGF-I and improves growth in uremia. We investigated whether exogenous IGF-I is also able to improve uremic growth failure in rats and whether the growth promoting effects of GH and IGF-I are additive. In female 150 g uremic (subtotal nephrectomy, NX) Sprague-Dawley rats, both rhGH in doses from 2 X 1.25 to 2 X 10 IU/kg bid s.c. and rhIGF-I in doses from 2 X 0.5 to 2 X 4.0 mg/kg bid s.c. caused a dose-dependent increase in weight gain and length gain. However, endogenous production of GH was suppressed by both agents. Peptide hormone treatment did not affect cumulative food intake, but significantly increased food efficiency ratio (weight gain/food intake). Concomitant s.c. treatment with maximally effective doses of rhGH (12 X 5 IU/kg bid) and of rhIGF-I (2 X 2 mg/kg bid) resulted in additive growth promoting effects in NX and pair-fed control (CO) animals during the observation period of 12 days. Cumulative length gain was 3.2 +/- 0.5 cm in solvent-treated NX-animals, 4.1 +/- 0.5 cm with rhGH (+ 28% above solvent), 4.2 +/- 0.6 cm with rhIGF-I (+ 31%) and 4.9 +/- 0.5 cm with both peptides (+ 53%). The food efficiency ratio was 0.16 +/- 0.05 in solvent NX, 0.33 +/- 0.04 with rhGH (+ 106% above solvent), 0.23 +/- 0.02 with rhIGF-I (+ 44%), and 0.38 +/- 0.02 with both peptides (+ 138%). Histomorphometric analysis and measurements of length gain by fluorescence microscopy in the upper tibial metaphysis confirmed the growth promoting effects of both peptide hormones. The serum concentrations of IGF binding protein (BP)-4 (Western ligand blotting analysis) and of IGFBP-2 (immunoblot) were increased in uremic animals whereas IGFBP-3 was unchanged. Treatment with IGF-I and/or rhGH increased serum concentration of IGF-I but did not change the IGFBP pattern. rhIGF-I lowered blood glucose levels within one to two hours after injection. The effect was most pronounced during the first treatment day and declined thereafter. Concomitant treatment with rhGH attenuated the glucose lowering effect of rhIGF-I (glucose serum concentration at day one: 120 +/- 11 mg% in solvent NX, 50 +/- 21 mg% with rhIGF-I, 80 +/- 24 mg% with both peptides). It is concluded that: (i) IGF-I is able to stimulate growth in NX animals but suppresses endogenous GH production in the long run; (ii) the concomitant treatment with IGF-I and GH has additive effects on growth; and (iii) concomitant treatment with rhGH prevents hypoglycemia that is noted with rhIGF-I alone.

Animals↗
PubMed1996

Influence of dialysis on plasma lipid peroxidation products and antioxidant levels.

In patients with end-stage renal failure (ESRF), the incidence of atherosclerosis and cancer is increased. The importance of lipid peroxidation (LPO) products in the pathogenesis of these complications has recently been emphasized. The LPO products malondialdehyde (MDA) and hexanal, lipophilic antioxidants and erythrocyte glutathione (GSH) were estimated in 10 pediatric hemodialysis (HD) patients before and after HD and in 11 peritoneal dialysis (CPD) patients. Before HD, MDA was elevated [median (interquartile range): 384.5 (110 to 501) nM; normal < 150 nM], whereas plasma hexanal levels were normal in all patients [130.5 (88 to 222) nM; < 320 nM]. HD decreased MDA concentrations on average by 88% but did not change hexanal levels. CPD patients exhibited high plasma MDA concentrations [371 (287 to 468) nM], whereas hexanal was in the low normal range [56 (51 to 81) nM]. Antioxidants were normal in both groups and unchanged during HD. GSH decreased slightly during HD. We hypothesize that MDA may accumulate in ESRF due to reduced plasma clearance. Our results argue against a general increase of LPO in uremia.

Adolescent↗
PubMed1996

Transplantation Report. 2: Pre-emptive renal transplantation in adults aged over 15 years. The EDTA-ERA Registry. European Dialysis and Transplant Association-European Renal Association.

Between 1985 to 1992, 2545 renal transplantation (RTx) were performed as pre-emptive grafts in adults. This procedure represented 7.2% of first RTx for patients starting first renal replacement therapy (RRT) during this period, 6.1% of RTx performed in 1992 and 5.6% of all RTx ever performed and reported to the EDTA Registry. The procedure is more frequent in cases of live donor grafts, representing one third of pre-emptive RTx. Both 5 year patient and graft survivals are unaffected by dialysis duration prior to the first RTx: none in pre-emptive, < 1 years, 1-5 years or > 5 years. In our personal view, this procedure should be developed.

Adolescent↗
PubMed1996

Insulin-like growth factor-I action on glucose transport in acute renal failure.

Insulin resistance is common in acute renal failure (ARF). Insulin-like growth factor (IGF)-I has insulin-like actions. The present study was undertaken to determine whether effects of IGF-I on glucose transport are maintained in rats with ARF and to compare these actions of IGF-I with those of insulin. ARF was induced in male Sprague-Dawley rats by bilateral ureteric ligation, and vascular catheters were inserted at the same time in all animals. Sham-operated controls were pair fed, and metabolic studies were performed 48 h later. ARF rats had higher serum creatinine (1.3 +/- 0.2 mg/dl vs. 0.3 +/- 0.1), lower arterial pH (7.15 +/- 0.03 vs. 7.35 +/- 0.02), and higher fasting serum glucose (150 +/- 13 vs. 123 +/- 12 mg/dl) compared with control rats (P < 0.001 in all cases). The hypoglycemic effects of insulin and IGF-I were compared using euglycemic clamps. In control rats, rates of total body glucose uptake were not different during euglycemic insulin clamps at 2 mU.kg-1.min-1 and euglycemic IGF-I clamps at 5 micrograms.kg-1.min-1. In rats with ARF, total body glucose uptake during euglycemic insulin clamps at 2 mU.kg-1.min-1 was significantly reduced (6.5 +/- 0.5 mg.kg-1.min-1) compared with controls (10.5 +/- 1.5 mg.kg-1.min-1, P < 0.01). In contrast, total body glucose uptake during euglycemic IGF-I clamps at 5 micrograms.kg-1.min-1 in ARF rats (10.1 +/- 1.2 mg.kg-1.min-1) was not different from the corresponding value in control animals (10.3 +/- 1.3 mg.kg-1.min-1). Hepatic glucose production was suppressed by insulin equally but not suppressed by IGF-I in both groups. In a second experiment, ARF was induced by bilateral renal ischemia. The following groups of animals were studied: ARF + NaCl, ARF + NaHCO3, and control + NaCl. Insulin and IGF-I clamps were performed as above. Correction of acidosis partially corrected insulin resistance but did not affect IGF-I sensitivity. Thus the capacity of IGF-I infusion to stimulate glucose uptake is maintained in ARF rats, which are insulin resistant.

Acute Kidney Injury↗
PubMed1996

Growth hormone as a new treatment modality for short children with chronic renal failure. The German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

Recombinant human growth hormone (rhGH) has become a new treatment modality for short children with chronic renal failure (CRF) and after renal transplantation. The rationale for high-dose rhGH treatment is the insensitivity of the uremic organism to GH. As the insensitivity to GH is expressed more in end-stage renal failure than in earlier stages of CRF, patients on dialysis respond less to rhGH. In transplanted children, rhGH can counterbalance the growth-depressing effects of corticosteroids. In prepubertal children, rhGH improves the height standard deviation score by a mean of +2 within 5 years. The effect of rhGH treatment on final height remains to be studied.

Child↗
PubMed1996

Multifactorial control of the elimination kinetics of unbound (free) growth hormone (GH) in the human: regulation by age, adiposity, renal function, and steady state concentrations of GH in plasma.

To evaluate the principal determinants of the MCR and plasma t1/2 of unbound (free) GH in man, we performed steady state infusions of 3 doses of recombinant human GH during pharmacological suppression (iv octreotide) of endogenous GH secretion in 24 healthy adults and 12 patients (6 adults and 6 children) with chronic renal failure (CRF). Free plasma GH was calculated from total plasma GH (measured by immunoradiometric assay) and GH-binding protein activity (radioligand assay). The MCR of free GH was determined from free plasma GH and the rate of recombinant human GH infusion. The t1/2 of free plasma GH, and the concentration and the in vivo dissociation constant (Kd) of GH-binding protein (GHBP) were estimated by dynamic modeling of the postinfusion total plasma GH concentration decay curves. The MCR of free GH decreased and the plasma GH t1/2 increased significantly with increasing plasma GH concentrations. The MCR of free GH over its physiological concentration range was positively correlated with the body mass index as a measure of relative obesity and negatively related to age, but only at supraphysiological GH concentrations. In the adult patients with CRF, the MCR of free GH was decreased at each infusion rate by 25-38%, and the t1/2 was increased by 80-170%. Children with CRF showed a significantly lower MCR and higher t1/2 of plasma free GH than adult patients. Modeling and direct measurements of the off-rate of GH from its high affinity GHBP indicated normal dissociation rate constants but decreased molar concentrations of the GHBP in uremic plasma. We conclude that the rate of elimination of free GH from plasma in man is controlled by 1) plasma total free GH concentrations, 2) relative obesity, and 3) renal function within the physiological GH concentration range, whereas 4) age is a negative predictor of MCR only at supraphysiological GH concentrations.

Adolescent↗
PubMed1996

Control of pulsatile and tonic parathyroid hormone secretion by ionized calcium.

To investigate the effect of changes in ionized calcium on instantaneous PTH secretion, we examined seven young healthy volunteers by 1-min blood sampling under conditions of normo-, hypo-, and hypercalcemia. After a baseline period of 75 min, ambient ionized calcium was either increased or decreased by 0.2 mmol/L for 105 min by clamped infusion of calcium gluconate or sodium citrate. The characteristics of PTH secretion were analyzed by a deconvolution technique, accounting for subject-specific plasma PTH disappearance half-life, as measured during the first 15 min of calcium infusion (range, 2.04-2.93 min). The process regularity of pulsatile PTH secretion was evaluated by an approximate entropy statistic. Under baseline conditions, 32% of total PTH secretion was released in a pulsatile fashion, with a burst frequency of 6.9 +/- 0.8 h-1 and a PTH mass per burst of 2.6 +/- 0.9 pmol/L. The remaining 68% of total secretion was attributed to tonic hormone release. During the initial 30 min of induced hypocalcemia, pulsatile secretion increased by 1140%, whereas tonic secretion did not change. The preferential increase in pulsatile PTH secretion was mediated by a combined rise in burst frequency and mass released per burst. During subsequent steady state hypocalcemia, the tonic secretion rate increased (255% of baseline), whereas burst frequency and burst mass decreased (to 103% and 189% of the baseline values), restoring the baseline ratio of tonic to pulsatile PTH secretion. The regularity of PTH release increased during steady state hypocalcemia. During hypercalcemia, tonic secretion, burst mass, and burst frequency decreased by 75%, 82%, and 32%, respectively, and remained constant throughout the clamp period. We conclude that acute hypocalcemia elicits an immediate pulsatile and a delayed tonic secretory response of the parathyroid gland with increased regularity of PTH release. Acute hypercalcemia suppresses both the pulsatile and the tonic component of PTH secretion.

Adult↗
PubMed1996

Assessment of total body water in paediatric patients on dialysis.

BACKGROUND: Various anthropometric techniques are used to assess total body water in children on dialysis; however, their predictive accuracy and precision has not been validated. METHODS: We compared total body water measurements obtained by deuterium oxide (D2O) dilution with predictions of total body water from (1) height and weight, (2) skinfold measurements, and (3) bioelectrical impedance analysis, using previously published formulae for healthy children. Measurements were performed in 14 patients on peritoneal and in nine patients on haemodialysis, aged 4-22 years. RESULTS: In the total population of dialysed patients, weight was the strongest single predictor of total body water (R2 = 0.93), followed by the resistance index (RI = height2/impedance; R2 = 0.85) and height (R2 = 0.93). A prediction formula based on height and weight predicted total body water with a residual mean square error (RMSE) of 1.97 1 (coefficient of variation (CV) = 10.0%) and with a systematic overestimation of true total body water by 0.4%. A prediction equation based on skinfold measurements yielded a total body water estimate with an RMSE of 2.15 1 (CV = 10.5%) and overpredicted true total body water by an average of 2.2%. Using three published prediction equations incorporating RI, RMSEs of 2.78 1 (CV = 14.1%) with a mean under- or overestimation of true total body water by 6.9, 7.1, and 0.8% respectively, were achieved. The prediction of total body water was optimized by linear combinations of RI or the log-transformed sum of four skinfolds (logsum) with weight by the following equations: total body water (1) = 9.97 - 3.13 x logsum (1) +0.59 x weight (kg) (R2 = 0.951; RMSE = 1.67 1; CV = 8.17%). total body water (1) = 1.99 + 0.144 x RI (Ohm/cm2) (2) + 0.40 x weight (kg) (R2 = 0.949; RMSE = 1.67 1; CV = 8.53%). The fit of these prediction formulae, which were derived from the total population, did not differ significantly between haemo- and peritoneal dialysis patients or between boys and girls. CONCLUSIONS: Both skinfold measurements and bioelectrical impedance analysis can be used to improve the height- and weight-based prediction of total body water in children on dialysis.

Adolescent↗