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Biomedical subjects

F Schaefer

Publications and source records attributed to F Schaefer.

At least 55 records · Page 3Linked to original sources
PubMed1998

Impact of recurrent nephrotic syndrome after renal transplantation in young patients.

Recurrent disease is a frequent complication of patients transplanted for steroid-resistant nephrotic syndrome associated with focal segmental glomerulosclerosis. Its long-term prognosis has rarely been studied. We examined 39 patients aged 4-25 (mean 13.5) years at the time of first transplantation (TX). Twelve of these (30%) developed nephrotic syndrome after the first TX and 2 of 8 after the second TX. The mean observation period from first TX to last observation with a functioning graft or graft loss was 5.4 (0.1-19.3) years. We confirmed that recurrent disease is associated with older age at onset of the primary disease, shorter time from onset to end-stage renal disease, and diffuse mesangial proliferation in the initial kidney biopsy. Remissions occurred in all 3 children undergoing early repeated plasma exchange and in 1 adolescent following introduction of cyclosporin A 7 years after TX. At last observation 42% of relapsing and 48% of non-relapsing patients with a similar follow-up period had a functioning first graft. Median first graft survival was almost identical in the relapsing and the non-relapsing patients (4.3 vs. 4.2 years). Histological lesions of focal glomerulosclerosis were detected in the posttransplant biopsies of only 3 patients. In conclusion, young patients with nephrotic syndrome associated with focal segmental sclerosis have a similar graft survival with and without recurrence of the nephrotic syndrome.

Adolescent↗
PubMed1998

Effect of a silver device in preventing catheter-related infections in peritoneal dialysis patients: silver ring prophylaxis at the catheter exit study.

Catheter-related infections remain a significant cause of method failure in chronic peritoneal dialysis (PD) therapy. Given the increasing antibiotic resistance, such nonpharmacological strategies as local silver devices attract more interest. To establish whether a silver ring device (designed by Grosse-Siestrup in 1992) mounted onto the PD catheter and placed at the exit site at skin level is effective in preventing exit-site and other catheter-related infections, a prospective 12-month, multicenter, controlled study stratified by diabetes status was conducted. The study subjects were assessed by an extensive structured inventory, including a broad spectrum of control variables, such as age, body mass index (BMI), Staphylococcus aureus carrier status, catheter features, mode and quality of PD therapy, comorbidity, and psychosocial rehabilitation. Ten experienced German outpatient dialysis centers (seven adult, three pediatric) participated in the trial. All eligible patients (n=195) from the study area without catheter-related infections during the ascertainment period were included (incidental subjects undergoing PD therapy for at least 3 months). The main outcome measures were the occurrence of first exit-site infections (primary study end point), sinus tract/tunnel infection, and peritonitis. Ninety-seven patients were assigned to the silver ring and 98 patients to the control group. Baseline characteristics of age, sex, proportion of pediatric and incidental patients, S aureus carrier status, and other variables were similar in both groups. The incidence of infections in the silver ring group versus the control group was as follows: 23 of 97 versus 16 of 98 patients had exit-site infections, 12 of 97 versus 12 of 98 patients had sinus tract/tunnel infections, 16 of 97 versus 18 of 98 patients had peritonitis, respectively. Kaplan-Meier analysis for the probability of an infection-free interval showed no statistical difference (log-rank test) between the two groups. Displacement of the silver ring contributed to study termination in 6% of the study group patients, including two patients with catheter loss. Univariate analysis and multiple logistic regression identified younger age (<50 years), low serum albumin level (<35 g/L), number of previously placed PD catheters, short cuff-exit distance (<2 cm), and S aureus nasal carriage as risk factors for the development of exit-site infections. In conclusion, our study does not show any benefit of the silver ring in preventing catheter-related infections in PD patients. Thus, prevention of infection-related method failure in PD still has to rely on conventional antibiotic treatment strategies and less so on alternative methods.

Adult↗
PubMed1998

Body mass index and percentage fat mass in healthy German schoolchildren and adolescents.

OBJECTIVE: To provide reference data for obesity indices in Mid-European schoolchildren and adolescents, to evaluate the usefulness of body mass index (BMI) as an indicator of obesity in children, and to analyse the patterns of fat accumulation during childhood. DESIGN: Cross-sectional observational study in 2554 healthy schoolchildren and adolescents (age, 6-19 y) living in Heidelberg, Germany in 1989/1990. Centile charts for BMI and skinfold-derived percentage body fat mass (PFM) were constructed using Cole's LMS method for normalised growth standards. RESULTS: The BMI centile values of German children ranged higher than French, lower than North American and Italian, and similar to Swedish and British children. While BMI steadily increased with age, PFM was markedly lower in peripubertal than in pre- and postpubertal boys. BMI predicted PFM with reasonable precision in girls (r=0.84), and in obese boys (r=0.58), but not in the leaner two thirds of the male population (r=0.01, NS). The 75th BMI percentile was the most appropriate cutoff value to screen for the 15% most obese patients by PFM (sensitivity: 82%, specificity: 85%). The pattern of the trunk-to-extremity skinfold ratio across childhood suggested that the typical adult distribution of central and peripheral fat is achieved in mid puberty in girls, but not before the end of adolescence in boys. CONCLUSIONS: The major differences observed between BMI charts obtained in different countries underline the need for population-specific reference data. BMI is of limited usefulness in predicting relative fat mass in individual children. The developmental pattern of fat accumulation and distribution during adolescence is highly dynamic and gender-specific.

Adipose Tissue↗
PubMed1998

Estimation of peritoneal mass transport by three-pore model in children.

BACKGROUND: Computerized modeling is increasingly used to optimize the efficacy of peritoneal dialysis (PD). The Personal Dialysis Capacity (PDC) test is a new tool to model PD efficacy based on the three-pore model of peritoneal mass transport. We sought to evaluate (i) whether the PDC test is applicable to children on chronic PD, and (ii) whether the physiological mass transport coefficients defined in the three pore model are dependent on age or body size in childhood. METHODS: A validation study was performed in 32 pediatric chronic PD patients. Twenty tests were performed using a standard CAPD regimen, and 22 tests using a simplified automated PD (APD) protocol. Test accuracy and precision were evaluated by comparison of predicted with measured 24-hour dialysate clearances of urea, creatinine, beta2-microglobulin and albumin and ultrafiltration rates. Long-term reproducibility was assessed in 16 patients by repeated clearance studies after a median time interval of 10 weeks. RESULTS: While daily clearances of urea and creatinine were predicted with good precision and accuracy with both test protocols (concordance correlation coefficients 0.90 to 0.98, mean difference predicted-calculated -0.6 to +0.6 ml/min/1.73 m2), ultrafiltration rates were predicted more closely by the APD (r = 0.97) than by the CAPD test (0.80). Middle and large molecule clearances were predicted less precisely in both test settings (r = 0.48 to 0.83). Re-test reproducibility was slightly lower than the predictive precision observed in the original test (r = 0.80 to 0.91). The calculated total peritoneal pore area increased in absolute terms, decreased with body size when standardized to weight, and was independent of body size when normalized to body surface area. The body size-normalized fluid reabsorption rate was slightly increased in young infants compared to older children or adults. CONCLUSIONS: The PDC test permits to model peritoneal solute and water transport with remarkable precision in children of all age groups. While the peritoneal pore area is a linear function of body surface area, fluid reabsorption appears to be slightly increased in young infants.

Adolescent↗
PubMed1998

Percutaneous renal biopsy in children: a 27-year experience.

BACKGROUND: The introduction of automated biopsy devices and the localization of the kidney by ultrasound were aimed at optimizing efficacy and safety of the percutaneous renal biopsy procedure. We evaluated these technological advances in our renal biopsies performed in children. METHODS: We sequentially used the Silverman needle (1969-1974), the TruCut needle (1974-1990), and the automated Biopty device (1990-1996). Fluoroscopy was used to localize the kidney until 1985, ultrasound examination prior to biopsy from 1985 to 1992, and direct ultrasound guidance since 1992. A total of 962 native kidney biopsies and 119 allograft biopsies were performed. RESULTS: In the native kidney biopsies, the introduction of the Biopty device and ultrasound guidance were independently associated with fewer passes required to obtain adequate tissue and more glomeruli per specimen. The rate of biopsies yielding more than 9 glomeruli increased from 69 to 92% (p < 0.05). The number of glomeruli harvested per centimeter core length was inversely related to patient age (p < 0.01). More appropriate cortical tissue was retrieved in renal allograft biopsy specimens with the application of the new techniques. The occurrence of macroscopic hematuria (9. 6%) in the native kidney biopsies was not affected by the puncture or localization technique applied, but subcapsular hematomas were documented more often with the Biopty device (42%) than with the TruCut needle (16%), probably due to improved ultrasound equipment. In the whole series 2 patients died, and 3 others required renal surgery and 4 blood transfusions. CONCLUSIONS: The automated ultrasound-guided procedure is a feasible and reliable technique for percutaneous renal biopsy in children. It gives a greater yield of diagnostic tissue without increasing the rate of clinical complications.

Adolescent↗
PubMed1998

Metabolic effects of long-term growth hormone treatment in prepubertal children with chronic renal failure and after kidney transplantation. The German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

To evaluate the metabolic effects of long-term treatment with recombinant human (rh) GH in short children with chronic renal failure (CRF), annual oral glucose tolerance tests (oGTT) during rhGH therapy for up to 5 y in 53 prepubertal children with CRF on conservative treatment, dialysis, and after renal transplantation were compared with that of 12 age-matched children treated with rhGH for idiopathic short stature. At the start of rhGH treatment, fasting values of glucose, insulin, glycosylated Hb A (HbA1C), triglycerides, cholesterol, glucose, and insulin responses during oGTT were significantly elevated in all patient groups compared with control subjects (p < 0.001). In the total population, fasting and 2-h postprandial glucose concentrations were inversely correlated with GFR and positively with age and methylprednisolone dosage in transplanted patients. Fasting insulin levels were positively correlated with body mass index and inversely with GFR. RhGH treatment was not associated with a change in fasting or stimulated glucose concentrations in any treatment group throughout the observation period. In contrast, serum insulin levels increased during the first treatment year in all groups, resulting in a more marked elevation of integrated insulin levels in transplant (1402 +/- 179 pM) and dialysis (1025 +/- 114 pM) patients compared with conservatively treated patients (829 +/- 94 pM), and control subjects (719 +/- 89 pM) (p < 0.01). Hyperinsulinemia persisted in all treatment groups for up to 5 y of follow-up. In conclusion, age, renal function, and obesity are the major independent predictors of glucose tolerance in children with CRF. Long-term rhGH treatment does not affect glucose tolerance, but aggravates the preexisting hyperinsulinemia in children with end-stage renal disease. In concert with the dyslipidemia of uremia, the rhGH-promoted hyperinsulinemia may contribute to the long-term risk for premature atherosclerosis in patients with childhood onset CRF.

Blood Glucose↗
PubMed1998

Altered instantaneous and calcium-modulated oscillatory PTH secretion patterns in patients with secondary hyperparathyroidism.

The relative contributions of increased parathyroid cell mass and altered control mechanisms of parathyroid hormone (PTH) secretion in secondary hyperparathyroidism are still controversial. In this study, endogenous pulsatile PTH secretion was analyzed by the multiparameter deconvolution technique to differentiate alterations in cell mass-dependent (PTH burst mass) and regulation-dependent (frequency, synchrony, calcium responsiveness) PTH release in uremic patients. PTH concentration versus time profiles were obtained in 13 uremic and 16 healthy adults under baseline conditions and during acute hypo- and hypercalcemia. Plasma PTH half-life was increased in patients compared with control subjects (4.7+/-1.9 versus 2.6+/-0.1 min, P < 0.005). The baseline PTH secretion rate was elevated eightfold in the patients as a result of an increased PTH mass secreted per burst (17.1+/-4.7 versus 2.0+/-0.4 pM, P = 0.0001), higher burst frequency (8.0+/-0.3 versus 6.8+/-0.3 h(-1), P < 0.01), and a higher tonic secretion rate (343+/-99 versus 30+/-4 pM/h, P = 0.0001). Acute hypocalcemia elicited an immediate, frequency- and amplitude-mediated selective increase in the pulsatile secretory component, which was fractionally weaker in patients (+595%) than control subjects (+1755%, P < 0.001). The acceleration and the amplification of PTH bursts were 35 and 60% lower in the patient group. Acute hypercalcemia suppressed total PTH secretion by 79% in control subjects but only by 63% in patients (P < 0.002). PTH burst frequency was reduced during hypercalcemia by 30% in control subjects, but remained unchanged in patients. In conclusion, uremic hyperparathyroidism is mediated by a marked increase in glandular secretion, but also by reduced PTH elimination. The increased spontaneous PTH burst frequency and the blunted responsiveness to changes in Ca2+ indicate partial uncoupling of hyperplastic parathyroid glands from the physiologic regulatory mechanisms that direct pulsatile PTH release.

Adolescent↗
PubMed1998

Factors predictive of the short- and long-term efficacy of growth hormone treatment in prepubertal children with chronic renal failure. The German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

To evaluate the growth-stimulating effects of short- and long-term treatment with recombinant human growth hormone (rhGH) in growth-retarded children with chronic renal failure (CRF), 103 prepubertal children with CRF on conservative treatment (n = 74) or dialysis (n = 29) were treated with rhGH for up to 5 yr. rhGH treatment persistently increased standardized height (+ 1.6 SD scores) and predicted adult height (+7.7 cm, Tanner method) during the first 3 treatment years (P < 0.001 versus baseline), followed by percentile parallel growth during continued treatment. Both standardized height and predicted adult height were significantly more increased in conservatively treated than in dialyzed children (P < 0.001). Age, GFR, target height, and prestudy growth rate were identified as independent predictors of the response to rhGH treatment during the first and second treatment year. GFR and target height were positively correlated with the change in height SD score and the change in absolute or age-standardized height velocity. Age affected the growth response depending on which outcome measure was used: Although the first-year change in height SD score was inversely correlated with age, the change in absolute height velocity was independent of age, and the change in standardized height velocity was positively correlated with age. The growth response during the first treatment year positively predicted the long-term response. In conclusion, the short- and long-term growth response to rhGH treatment in prepubertal growth-retarded children with CRF is significantly affected by age, GFR, target height, and the pretreatment growth rate. Therefore, rhGH should be preferably started at a young age, and early in the course of CRF.

Age Factors↗
PubMed1998

1,25(OH)2-vitamin D3 reduces spontaneous and hypocalcemia-stimulated pulsatile component of parathyroid hormone secretion.

To investigate the effects of 1,25(OH)2-vitamin D3 (1,25(OH)2D3) on pulsatile parathyroid hormone (PTH) release, minute-to-minute intact PTH secretion was examined in nine healthy adults under baseline conditions and during hypocalcemia (sodium citrate clamp) before and after 5 d of oral 1,25(OH)2D3 treatment (1 microgram/d). In addition, acute effects of 1,25(OH)2D3 were examined by a single intravenous bolus of 2 micrograms of 1,25(OH)2D3. Pulsatile and tonic PTH secretion rates were calculated by the multiparameter deconvolution technique. During baseline, 68% of circulating PTH was attributable to tonic, and 32% to pulsatile, secretion. During induction of hypocalcemia, a selective increase in pulsatile secretion (+1100%), mediated by a combined increase in burst frequency and burst mass, was observed. During the subsequent steady-state hypocalcemic period, burst frequency and mass decreased and tonic secretion increased to 3 times the baseline level. Intravenous 1,25(OH)2D3 did not affect the temporal pattern of PTH secretion. In contrast, oral 1,25(OH)2D3 decreased baseline plasma PTH by 30% without a detectable change in Ca2+. This suppression was accounted for mainly by a decrease in PTH burst frequency. During hypocalcemia induction, a significantly lower (30%) increase in burst mass occurred compared with the pretreatment study. During steady-state hypocalcemia, PTH burst mass (-45%) and pulsatile (-50%) and total (-35%) secretion rate were lower than before treatment. In conclusion, acute hypocalcemia selectively increases pulsatile PTH release by stimulating both burst frequency and mass via a Ca2+ rate-sensitive mechanism. Oral 1,25-(OH)2D3 suppresses pulsatile baseline PTH release and reduces the pulsatile secretory capacity of the parathyroids during a hypocalcemic stimulus.

Administration, Oral↗
PubMed1998

Inappropriate elevation of serum leptin levels in children with chronic renal failure. European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood.

Decreased spontaneous nutrient intake is a frequent clinical problem in patients with chronic renal failure (CRF). Leptin, the recently characterized gene product of the obese gene, is produced by adipocytes and is thought to act as an afferent satiety signal on the appetite and satiety centers of the brain. Serum leptin levels were investigated in 134 pediatric patients in different stages of CRF to evaluate a possible relationship between leptin, GFR, and spontaneous energy intake. Serum leptin levels, measured by a specific RIA, were elevated above the 50th percentile of the normal range in 78% of CRF patients and above the 95th percentile in 45% of patients. Gel chromatography of CRF sera yielded only one single immunoreactive peak at 16 kD, indicating that the increase of immunoreactive leptin levels in CRF serum was not due to accumulation of leptin degradation products. Multiple stepwise regression analysis revealed the percentage of body fat as assessed from skinfold measurements (r = 0.79, P < 0.0001) and GFR (r = -0.17, P < 0.005) as independent predictors of serum leptin levels, accounting for 66% of total statistical variability. There was an inverse linear correlation between standardized leptin levels (leptin z-score) and the spontaneous energy intake quantified from written dietary diaries (r = -0.36, P < 0.001). These data suggest that the percentage of body fat remains the main determinant of serum leptin in CRF patients, but their levels increase with declining GFR, presumably by reduced renal clearance. Leptin levels in CRF serum that are inappropriately elevated in relation to the percentage of body fat might lead to a dysregulation of the normal peripheral-central leptin feedback loop, thereby contributing to decreased nutrient intake in uremia.

Adolescent↗
PubMed1997

Renal function and renotropic effects of secretin in cystic fibrosis.

In ten cystic fibrosis patients and nine age-matched controls, renal function was determined before and after infusion of secretin. Under baseline conditions creatinine excretion and clearance were significantly elevated, exclusively due to those patients who were homozygous for the DF508 mutation (153 vs 132 ml/min*1.73m2), whereas the glomerular filtration rate, measured by inulin clearance showed no difference. Renal plasma flow and the fractional reabsorption rates of electrolytes were similar in patients and controls. During secretin infusion renal plasma flow increased and the fractional reabsorption rates of electrolytes decreased in both groups. The patients had a increased metabolic clearance (2900 vs 1660 ml/min*m2) and endogenous production rate (9,9 vs 2,5 pmol/min*m2) of of secretin. In conclusion global renal function and electrolyte handling, in particular chloride permeability, are unchanged in cystic fibrosis. Individuals expressing the DF508 genotype showed a selective elevation of creatinine excretion and clearance. The secretion and metabolic clearance of secretin are increased in cystic fibrosis.

Adolescent↗
PubMed1997

Randomised multicentre study of a low-protein diet on the progression of chronic renal failure in children. European Study Group of Nutritional Treatment of Chronic Renal Failure in Childhood.

BACKGROUND: Some studies have suggested that a low-protein diet slows the deterioration of renal function in patients with chronic renal failure (CRF). The effects of a low-protein diet on renal function and growth, have not been assessed in a large, prospective randomised trial in children with CRF. METHODS: A 2-year prospective, stratified, and randomised multicentre study recruited 191 patients aged 2-18 years. After a run-in period of at least 6 months, patients were stratified into either a progressive or non-progressive category based on the change in creatinine clearance in this period. The patients were also stratified into three renal-disease categories and then randomly assigned to a control or diet group. In the diet group, the protein intake was the lowest, safe WHO recommendation--i.e., 0.8-1.1 g/kg daily adjusted for age. All patients were advised to have a calorie intake of at least 70% of the WHO recommendations. Glomerular filtration rate (GFR) was measured every 2 months by creatinine clearance; dietary compliance was checked by urinary urea-nitrogen excretion and dietary diaries (weighing method). 112 patients completed an optional third year of the study. FINDINGS: The low-protein diet did not affect growth. However, there was no effect of diet on the mean decline in creatinine clearance over 2 years (diet vs control: progressive group -9.7 [SD 8.0] vs -10.7 [11.8] mL/min per 1.73 m2; non-progressive group -2.5 [7.5] vs -4.3 [10.0] mL/min per 1.73 m2). Patients classified as having progressive disease were older and had a lower creatinine clearance and a higher blood pressure at randomisation, and had a greater decrease in creatinine clearance than non-progressive patients. On multivariate regression analysis proteinuria (partial R2 = 0.259) and systolic blood pressure (partial R2 = 0.087) were independent predictors of the change in GFR. Similar results were found after the study was extended for a third year. INTERPRETATION: A low-protein diet for 3 years did not affect the decrease in renal function in children with CRF. Proteinuria and blood pressure explain a large part of the variability of, and may be causally related to the decline in the GFR.

Adolescent↗
PubMed1997

Abnormal pulsatile secretion of growth hormone in non-insulin-dependent diabetes mellitus.

OBJECTIVE: Studies of GH secretion in patients with non-insulin dependent diabetes mellitus (NIDDM) have produced conflicting results. We aimed to differentiate the effects of obesity and metabolic control on pulsatile GH secretion in patients with NIDDM. DESIGN: Blood sampling every 15 min from 22.00 hours to 08.00 hours after a fasting period of at least 3 h. PATIENTS: 13 male NIDDM patients, 9 healthy control subjects matched for age and BMI, and 6 lean subjects matched for age. MEASUREMENTS: Measurement of GH by a novel ultrasensitive chemiluminescence assay. Analysis of concentration vs time profiles by a multiparameter deconvolution technique. RESULTS: GH burst frequency was increased in the NIDDM (0.82 +/- 0.28 h-1) compared with both control groups (lean: 0.6 +/- 0.11; obese: 0.56 +/- 0.19). GH burst mass was decreased in patients (1.57 +/- 0.98 micrograms/l.min) and in obese controls (1.46 +/- 1.44) compared to lean controls (3.71 +/- 3.88). These differences resulted in a significantly higher nocturnal pulsatile GH secretion rate in the lean compared to the obese controls, whereas in the patient group enhanced GH burst frequency compensated for reduced burst mass. The characteristics of GH secretion were not related to nocturnal or early morning blood glucose concentrations. However, GH secretion rate was correlated positively with HbA1c (r = 0.57; P = 0.04), and negatively with plasma C peptide concentrations. CONCLUSIONS: The specific increase in GH burst frequency previously described in insulin-dependent diabetes mellitus is also present in NIDDM. However, GH hypersecretion does not occur because GH burst mass is reduced in proportion to the degree of obesity. The effect of diabetes on the hypothalamic control of GH release appears to be determined by the quality of long-term glycaemic control.

Analysis of Variance↗
PubMed1997

Angiotensin II affects basal, pulsatile, and glucose-stimulated insulin secretion in humans.

Angiotensin II (Ang II) modulates the tissue response to insulin (insulin sensitivity), but the effect of Ang II on the secretion of insulin has not been investigated thus far. Nineteen healthy volunteers (17 male; mean age, 26+/-1 years) were studied. In a double-blind, randomized, placebo-controlled study, seven volunteers were allocated on three occasions in random order after an overnight fast to three interventions: (1) solvent (placebo) infusion; (2) infusion of 1.0 ng Ang II x kg(-1) x min(-1) (subpressor dose); and (3) infusion of 5.0 ng Ang II x kg(-1) x min(-1) (pressor dose). Frequent blood samples (each minute) were obtained for estimation of plasma insulin concentrations over a period of 120 minutes to assess basal and pulsatile insulin secretion. In an ancillary study, plasma glucose and insulin levels were measured after an oral glucose tolerance test while solvent (placebo) or Ang II was infused in 12 fasting healthy volunteers. Plasma insulin concentrations were measured immunoenzymatically (enzyme-linked immunosorbent assay). Insulin secretion pulses were analyzed with the deconvolution technique, and the regularity of insulin secretion was analyzed with the approximate entropy technique. Plasma insulin half-life was assessed using the hyperinsulinemic euglycemic clamp method. The pressor dose of Ang II reduced total, basal, and pulsatile insulin secretion, and this effect was highly significant (P<.01). The subpressor dose tended to suppress insulin secretion. The burst frequency (number of peaks) and the regularity of insulin secretion were not affected by administration of Ang II. After the oral glucose load, the insulinemic response was significantly lower and plasma glucose concentrations were significantly higher with infusion of Ang II compared with placebo. Ang II affects both the basal (nonpulsatile) and the pulsatile component of spontaneous insulin secretion and the glucose-stimulated insulin secretion in humans. This observation is of potential interest with respect to the interaction of Ang II and insulin, eg, in the genesis of hyperinsulinemia and hypertension.

Adult↗
PubMed1996

Preproinsulin I and II mRNAs and insulin electron microscopic immunoreaction are present within the rat fetal nervous system.

Insulin-like substance has been found within the nervous system. In the rat, preproinsulin II mRNA was shown within the brain and preproinsulin I mRNA within the retina. The present study demonstrates the presence of preproinsulin mRNAs within the 15, 17 and 19 day gestational age fetal rat brain, spinal cord and dorsal root ganglia (DRG), employing RNA template-specific polymerase chain reaction (RS-PCR), semi-nested PCR and RNase protection assay. Preproinsulin I mRNA was present in the 17 and 19 day gestational age brain, spinal cord and DRG, and only in the brain of the 15 day gestational age brain. Preproinsulin II mRNA was present in all the gestational ages studied in the brain, spinal cord and DRG. The RS-PCR and the semi-nested PCR demonstrated products that co-migrated with the pancreatic control. The semi-nested products were characterized as preproinsulin I and II by restriction enzyme digestion and sequence. RNase protection assay using specific cRNA for preproinsulin I and II showed a band that co-migrated with pancreatic preproinsulin I and II mRNAs, and confirmed the PCR results. In addition, insulin receptor mRNA was detected by RS-PCR. Ultrastructural studies showed insulin immunoreaction within the endoplasmic reticulum, Golgi apparatus, cytoplasm, axon, dendrites, and in relation to the synapses. Thus, we demonstrated the presence of preproinsulin I and II mRNA, insulin receptor mRNA and insulin immunoreaction within the rat fetal central and peripheral nervous system.

Animals↗
PubMed1996

Early age-dependent growth impairment in chronic renal failure. European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood.

We report early linear growth in 73 children (51 boys, 22 girls) with early onset of chronic renal failure (CRF). The inclusion criteria was onset of CRF before 6 months of age, two or more height measurements during the 1st year of life, follow-up for at least 3 years and continuously impaired renal function with a glomerular filtration rate below 50 ml/min per 1.73 m2 at 1 year or later. Only height measurements taken during conservative treatment or dialysis were included. The data were analysed in terms of the infancy-childhood-puberty growth model. There was an age-dependent growth failure in early life leading to an attained height of -3 standard deviation score (SDS) at 3 years of age. Approximately one-third of the reduction in height occurred during fetal life and one-third during the first postnatal months. Between 0.75 and 1.5 years of age height also decreased by 1 SD as a consequence of a delayed onset of the second, the 'childhood', phase of growth in 36% of the patients and by an 'offset childhood' growth pattern--i.e. a return to the infancy phase pattern after onset of the childhood phase--in 60% of the patients. Growth between 0.25-0.75 and 1.5-5 years of age was generally percentile parallel and thus less likely to be affected in CRF with early disease onset. The glomerular filtration rate was not related to the height gain in early life. We speculate that the growth failure during fetal life and the first postnatal months reflects metabolic and/or nutritional influences and the impaired growth at 0.75-1.5 years of age is related to a partial insensitivity to growth hormone.

Aging↗
PubMed1996

Growth charts for prepubertal children with chronic renal failure due to congenital renal disorders. European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood.

Despite the high prevalence of and therapeutic attention to growth failure in children with chronic renal failure (CRF), systematic evaluations of spontaneous growth in CRF are lacking. Therefore, we collected retrospectively longitudinal growth and biochemical data in 321 prepubertal patients treated for CRF due to congenital renal disorders. Data were recorded at 3-month intervals during the first 2 years of life and 6-monthly thereafter, up to the age of 10 years. Around 100 measurements were available per age interval. Mixed-longitudinal percentile curves of height and height velocity were constructed. Moreover, a statistical comparison with the heights and height velocities of healthy children and an evaluation of the effect of biochemical parameters on growth was performed. The CRF children had normal heights at birth but dropped below the 3rd normal percentile during the first 15 months of life. Thereafter, growth patterns usually were percentile parallel, with a mean height standard deviation score (SDS) of -2.37 +/- 1.6. Height velocities were consistently lower in patients with glomerular filtration rates (GFRs) below one-third of the lower normal limit (25 ml/min per 1.73 m2 for patients > 1 year) than in patients with better renal function. This difference in growth rates resulted in a mean height SDS of -1.65 +/- 1.5 SDS and -2.79 +/- 1.4 SDS (age 1-10 years) in the subgroups with relatively better and worse GFR, respectively. Regression analysis confirmed that GFR was a weak but significant predictor of height velocity SDS in most age groups.

Child↗