Magnetic topology changes induced by lower hybrid waves and their profound effect on edge-localized modes in the EAST tokamak.

Strong mitigation of edge-localized modes has been observed on Experimental Advanced Superconducting Tokamak, when lower hybrid waves (LHWs) are applied to H-mode plasmas with ion cyclotron resonant heating. This has been demonstrated to be due to the formation of helical current filaments flowing along field lines in the scrape-off layer induced by LHW. This leads to the splitting of the outer divertor strike points during LHWs similar to previous observations with resonant magnetic perturbations. The change in the magnetic topology has been qualitatively modeled by considering helical current filaments in a field-line-tracing code.

Diffusion in a collisional standard map.

Test particle evaluation of the diffusion coefficient in the presence of magnetic field fluctuations and binary collisions is presented. Chaotic magnetic field lines originate from resonant magnetic perturbations (RMPs). To lowest order, charged particles follow magnetic field lines. Drifts and interaction (collisions) with other particles decorrelate particles from the magnetic field lines. We model the binary collision process by a constant collision frequency. The magnetic field configuration including perturbations on the integrable Hamiltonian part is such that the single particle motion can be followed by a collisional version of a Chirikov-Taylor (standard) map. Frequent collisions are allowed for. Scaling of the diffusion beyond the quasilinear and subdiffusive behaviour is investigated in dependence on the strength of the magnetic perturbations and the collision frequency. The appearance of the so called Rechester-Rosenbluth regime is verified. It is further shown that the so called Kadomtsev-Pogutse diffusion coefficient is the strong collisional limit of the Rechester-Rosenbluth formula. The theoretical estimates are supplemented by numerical simulations.

Numerical modeling of edge-localized-mode filaments on divertor plates based on thermoelectric currents.

Edge localized modes (ELMs) are qualitatively and quantitatively modeled in tokamaks using current bursts which have been observed in the scrape-off-layer (SOL) during an ELM crash. During the initial phase of an ELM, a heat pulse causes thermoelectric currents. They first flow in short connection length flux tubes which are initially established by error fields or other nonaxisymmetric magnetic perturbations. The currents change the magnetic field topology in such a way that larger areas of short connection length flux tubes emerge. Then currents predominantly flow in short SOL-like flux tubes and scale with the area of the flux tube assuming a constant current density. Quantitative predictions of flux tube patterns for a given current are in excellent agreement with measurements of the heat load and current flow at the DIII-D target plates during an ELM cycle.

Sheared plasma rotation in partially stochastic magnetic fields.

It is shown that resonant magnetic perturbations generate sheared flow velocities in magnetized plasmas. Stochastic magnetic fields in incomplete chaos influence the drift motion of electrons and ions differently. Using a fast mapping technique, it is demonstrated that a radial electric field is generated due to the different behavior of passing particles (electrons and ions) in tokamak geometry; magnetic trapping of ions is neglected. Radial profiles of the polodial velocity resulting from the force balance in the presence of a strong toroidal magnetic field are obtained. Scaling laws for plasma losses and the forms of sheared plasma rotation profiles are discussed.

Improved confinement due to open ergodic field lines imposed by the dynamic ergodic divertor in TEXTOR.

The ergodization of the magnetic field lines imposed by the dynamic ergodic diverter (DED) in TEXTOR can lead both to confinement improvement and to confinement deterioration. The cases of substantial improvement are in resonant ways related to particular conditions in which magnetic flux tubes starting at the X points of induced islands are connected with the wall. This opening process is connected with a characteristic modification of the heat deposition pattern at the divertor target plate and leads to a substantial increase and steepening of the core plasma density and pressure. The improvement is tentatively attributed to a modification of the electric potential in the plasma carried by the open field lines. The confinement improvement bases on a spontaneous density built up due to the application of the DED and is primarily a particle confinement improvement.

Clearance and removal of oxalate in children on intensified dialysis for primary hyperoxaluria type 1.

Patients with end-stage renal failure owing to primary hyperoxaluria type 1 (PH1) receive dialysis while waiting for transplantation. So far, dialysis has not been shown to overcome the problem of ongoing oxalate production and deposition at extrarenal sites. We report on six children with PH1 who had to be dialyzed for a median period of 2.5 years while awaiting liver transplantation. Aiming at preventing oxalate tissue accretion, oxalate mass transfer was studied and dialysis intensified accordingly. Mean plasma oxalate concentration was between 51 and 137 micromol/l. In three of the six patients with a urinary output between 630 and 3140 ml, urinary removal of oxalate was between 5.6 and 12.4 mmol/week/1.73 m2. Hemodialysis (HD) in five of the six patients demonstrated a mean oxalate dialysance between 158 and 444 l/week/1.73 m2. Peritoneal dialysis (PD) in two of the six patients showed mean oxalate clearances of 66 and 103 l/week/1.73 m2. One patient received HD and PD. By adding all modes of elimination, a mean total oxalate mass between 10.1 and 24.1 mmol/week/1.73 m2 was removed. Dialysis is still necessary as a temporary therapy for a number of patients with PH1. Dialysis should be instituted pre-emptively and maximally exploited by intensified HD/PD treatment protocols, without, however, cutting back urinary output.

Unusual manifestation of posttransplant lymphoproliferative disorder in the esophagus.

Early manifestations of posttransplant lymphoproliferative disorders (PTLD) are mainly associated with a primary Epstein-Barr virus (EBV) infection. Rapid increases in peripheral blood EBV DNA load are supposed to reliably predict PTLD. We report a boy who 6 months after living-related kidney transplantation presented with an extranodal esophageal manifestation of PTLD. Despite a primary EBV infection with tonsillitis, the peripheral blood EBV DNA remained low, hiding the progression to PTLD.

Pathomechanisms and the diagnosis of arterial hypertension in pediatric renal allograft recipients.

Arterial hypertension is common in pediatric renal allograft recipients. While the causes are multifactorial, including chronic graft rejection, immunosuppressive therapy, and renal vascular disorders, the effect of hypertension on renal allograft function is detrimental. As in adults, if not treated early and aggressively, hypertension may lead to cardiovascular damage and graft failure. Pathophysiological changes in the arteries and kidney af-ter renal transplantation and the impact of receptor regulation have not been studied extensively in children. For identifying children with hypertension following renal transplantation casual blood pressure measurements do not accurately reflect average arterial blood pressure and circadian blood pressure rhythm. Ambulatory 24-h blood pressure monitoring should regularly be applied in trans-plant patients. The purpose of this review is to analyze pathophysiological aspects of risk factors for arterial hypertension and underline the importance of regular blood pressure monitoring and early therapeutic intervention.

Impact of ACE I/D gene polymorphism on congenital renal malformations.

To investigate the role of the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism on prevalence and progression of disease in children with chronic renal failure (CRF), we determined the ACE I/D genotype in 95 children with CRF due to renal malformations (hypo-/dysplasia, obstructive uropathy, reflux nephropathy; n = 59), other congenital or hereditary diseases (n = 23), or acquired glomerular disorders (n = 13), who had been followed prospectively over a 2-year period. CRF progression rate was followed in each individual by linear regression analysis of estimates of glomerular filtration rate (GFR) obtained every 2 months. Actuarial renal 'survival' analysis was performed, using a GFR loss of 10 ml/min per 1.73 m2 as a cutoff point. The distribution of the ACE genotype did not differ among the disease groups. There was also no difference in ACE genotype distribution between the patients and a control group of healthy Caucasian children (n = 163). Among the children with renal malformations, the 2-year renal survival was significantly lower in those with the DD genotype (61%) than in patients with ID or II genotype (89%, P < 0.01). In the other disease groups, the ACE I/D genotype was not predictive of CRF progression. In a multivariate analysis of risk factors, the adverse effect of the DD genotype (risk ratio 10.2, P < 0.05) was independent of and additive to those of arterial hypertension (RR 13.2, P < 0.001) and gross proteinuria (RR 4.7, P < 0.05). We conclude that the ACE DD genotype is a significant risk factor for children with congenital renal malformations to develop progressive CRF. The effect of the ACE polymorphism in this patient group is independent of hypertension and proteinuria.

Ciprofloxacin-induced acute renal failure in a patient with cystic fibrosis.

Acute renal failure is a rare adverse reaction of antibiotic therapy with quinolones seldom seen in young patients. We report an 18-year-old young woman with cystic fibrosis who experienced a pronounced decline in renal function after oral treatment with ciprofloxacin for 3 weeks. Withdrawal of the drug led to normalization of renal function after 10 days.

Platelet adenylyl cyclase signaling remains unaltered in children undergoing hemodialysis treatment.

Patients with chronic renal failure exhibit multiple endocrine, gastrointestinal and cardiovascular abnormalities, many of which may be explained by alterations of adenylyl cyclase (AC) responsiveness and/or G-protein expression. Since such alterations were previously reported, e.g., for platelets of adult chronic renal failure patients undergoing hemodialysis treatment (HD), we have investigated whether children with chronic renal failure undergoing HD exhibit similar alterations. Eleven uremic children undergoing HD were compared with 11 age-matched healthy controls. Platelet AC activity was determined in the absence (basal) and presence of a receptor agonist, direct G-protein activators and direct AC stimulators. G-protein alpha-subunits were measured by quantitative immunoblotting. Basal and stimulated platelet AC and immunoreactivity for platelet G-protein alpha-subunits did not significantly differ between HD and control children. We conclude that HD in children is associated with much smaller, if any, abnormalities of blood cell signal transduction than in adult patients. We speculate that quality of dialysis, age, and underlying disease might differentially influence blood cell signal transduction cascades.

Hypothyroidism mimicking chronic renal failure in reflux nephropathy.

An adolescent with a history of pyelonephritis and renal scarring had antireflux surgery at the age of 2.5 years. His serum creatinine was high at the age of 14 years (133 micromol/l; glomerular filtration rate (GFR) 56 ml/min x 1.73 m(2)), and reflux nephropathy with chronic renal failure was diagnosed. Because of a fall in height velocity, endocrinological investigations were performed six months later which showed hypothyroidism caused by autoimmune thyroiditis. Substitution with thyroxine was started; renal function improved to normal six months later (GFR 108 ml/min x 1.73 m(2)). Metabolic changes of hypothyroidism led to a reduction of GFR in this patient and mimicked chronic renal failure.

Serum insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5 in children with chronic renal failure: relationship to growth and glomerular filtration rate. The European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood. German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

Growth retardation in children with chronic renal failure (CRF) is partly due to an inhibition of insulin-like growth factor (IGF) activity by an excess of high-affinity IGF-binding proteins (IGFBPs). The aim of this study was to analyze the serum levels and forms of IGFBP-4 and IGFBP-5 in CRF patients using specific, recently developed radioimmunoassays (RIAs) and immunoblot analysis. We examined 89 children [age 11.5 (2.8-19.0) years] with CRF [glomerular filtration rate 26.6 (7.0-67.4) ml/min per 1.73 m2], nine of them with end-stage renal disease undergoing peritoneal dialysis. Serum-immunoreactive IGFBP-4 levels were fourfold increased in CRF (prepubertal 1080+/-268 ng/ml; pubertal 989+/-299 ng/ml) compared to healthy prepubertal controls (265+/-73 ng/ml). In contrast, serum IGFBP-5 levels were not significantly increased neither in prepubertal (361+/-120 ng/ml vs 282+/-75 ng/ml in controls) nor pubertal CRF children (478+/-165 ng/ml vs 491+/-80 ng/ml in controls). Immunoblot analysis showed the presence of intact as well as fragmented IGFBP-4 and IGFBP-5. Serum IGFBP-4, but not IGFBP-5, levels were inversely correlated with GFR (r=-0.39, P<0.001). In prepubertal children, IGFBP-4 levels were inversely correlated with standardized height (r=-0.40; P<0.005). In contrast, IGFBP-5 levels were positively correlated both with standardized height (r=0.32, P<0.02) and baseline height velocity (r=0.45, P<0.005). A 3-month therapy with rhGH stimulated serum IGFBP-5 levels by 43% (P<0.01); there was no consistent effect on IGFBP-4 levels. There was a positive correlation between IGFBP-4 and IGFBP-2 (r=0.46, P<0.001); IGFBP-5 was positively correlated with IGF-I (r=0.59, P<0.001), IGF-II(r=0.42, P<0.001)and IGFBP-3 (r=0.47, P<0.001) and inversely correlated with IGFBP-1 (r=-0.41, P<0.001). In summary, serum IGFBP-4 is fourfold elevated in children with CRF in relation to the degree of renal dysfunction and contributes to the marked increase in IGF-binding capacity in CRF serum. The inverse correlation of serum IGFBP-4 with standardized height is consistent with its role as another inhibitor of the biological action of the IGFs on growth plate cartilage. In contrast, serum IGFBP-5 is not elevated in CRF serum and circulates mainly as proteolysed fragments. The positive correlation of serum IGFBP-5 with growth and its increase during GH therapy indicate that IGFBP-5 is a stimulatory IGFBP in patients with CRF, either by enhancing IGF activity through better presentation of TGF to its receptor or by an IGF-independent effect through activation of a specific, recently described putative IGFBP-5-receptor.

[Quality of life following renal transplantation in childhood]. / Lebensqualität nach Nierentransplantation im Kindesalter.

The goal of renal transplantation is to achieve the best possible quality of life in patients with terminal renal failure. To evaluate some aspects of quality of life in patients with renal grafts during childhood of our center, data on medical, educational and professional rehabilitation were collected retrospectively. Between 1972 and 1997 135 renal transplantations had been performed in 123 patients below the age of 18 years. 12-year graft survival of patients transplanted before 1983 figured at 21% and rose to 62% during the following years, after introduction of cyclosporine A into the immunosuppressive regimen. The proportion of patients in the respective age group attending a secondary school (16%) was lower and of those attending elementary school (71%) or a school for disabled and handicapped children (11%) was higher than usual in the German population. But, 83% of all patients reached a school degree. After school 78% proceeded with a vocational training or university. 89% of patients completing professional training were employed at last observation as compared to only 60% of those who never finished a professional training. Renal replacement therapy starting already during the early phase of education is difficult to coordinate with normal schooling. Considering these health- and time-related obstacles, the degree of educational and professional rehabilitation of the patients is good. But, there is a need for special support accompanying educational and professional training.

Growth and weight gain in children with vesicoureteral reflux receiving medical versus surgical treatment: 10-year results of a prospective, randomized study. International Reflux Study in Children (European Branch).

In children with vesicoureteral reflux (VUR) and urinary tract infection, retardation of growth and weight gain at the time of diagnosis and catch-up growth during follow-up, mostly after operating for VUR, have been reported. A controlled trial comparing the effect on growth of surgical treatment and long-term prophylactic antibiotic treatment has not been reported previously. Between 1980 and 1985, 306 children younger than 11 y with non-obstructive grade III or IV VUR, with a history of symptomatic urinary tract infection, were randomly allocated to surgical or medical treatment. Of these, 236 were followed for 10 y, 118 randomized to surgical treatment (mean age at entry 3.5 +/- 2.3 y) and 118 to medical treatment (mean age at entry 3.8 +/- 2.5 y). All children had renal function and blood pressure in the normal range. Body height, measured at start and after 1, 5 and 10 y, was transformed to standard deviation score of height for chronological age (SDSH-CA) and body weight to percentage of ideal body weight for height (%IBW). The evolution of SDSH-CA and %IBW was similar in both treatment groups (SDSH-CA: surgical: start, 0.23 +/- 1.4; 10 y, 0.40 +/- 1.0; medical: start, 0.14 +/- 1.2; 10 y, 0.44 +/- 1.2; %IBW: surgical: start, 99 +/- 9%; 10 y, 107 +/- 14%; medical: start, 98 +/- 10%; 10 y, 105 +/- 16%). While children starting the study below the age of 3 y (SDSH-CA 0.55 +/- 1.34) started significantly taller than those older than 3 y (SDSH-CA -0.1 +/- 1.39), the young ones demonstrated a significant drop in SDSH-CA during the 1st year (SDSH-CA 0.19 +/- 1.23), which was regained up to the 10th year (SDSH-CA 0.6 +/- 1.13), and the older ones steadily gained height up to an SDSH-CA of 0.28 +/- 1.05 at 10 y. During all of the study period, treatment protocol, grade of VUR, renal parenchymal scars at entrance and urinary tract infections did not influence growth and weight gain. Age at entry and gender were the only significant correlates with growth and weight gain.

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.

Insulin-like growth factor-binding protein-6 levels are elevated in serum of children with chronic renal failure: a report of the Southwest Pediatric Nephrology Study Group.

Previous studies suggest that growth retardation in children with chronic renal failure (CRF) results in part from inhibition of insulin-like growth factor (IGF) action by excess serum IGF-binding proteins (IGFBPs). Excess IGFBPs in CRF serum include IGFBP-1, -2, and -3 and a diffuse approximately 24- to 28-kDa IGFBP band identified by [125I]IGF ligand blot. The present studies characterized this diffuse approximately 24- to 28-kDa band. Initial studies identified this band as IGFBP-6, because it was immunoprecipitated by antiserum raised against a synthetic peptide of human IGFBP-6 (hIGFBP-6). Additional [125I]IGF ligand blots found that the immunoprecipitated band was 1) recognized by [125I]IGF-II but not [125I]IGF-1, 2) more abundant in CRF than in normal serum, and 3) more abundant in serum from dialyzed than nondialyzed prepubertal CRF children. Using the hIGFBP-6 antiserum in a specific and sensitive RIA, we found that serum IGFBP-6 levels were 4.7 +/- 1.7 nmol/L in 10 normal prepubertal children, 21.4 +/- 6.1 nmol/L in 44 nondialyzed prepubertal CRF children, 73.5 +/- 14.4 nmol/L in 7 dialyzed prepubertal CRF children, and 94.6 +/- 26.2 nmol/L in 14 dialyzed pubertal CRF children. IGFBP-6 levels were also elevated in 71 nondialyzed European children with CRF. In nondialyzed CRF children, serum IGFBP-6 levels 1) correlated inversely with the glomerular filtration rate, 2) did not correlate with height SD score, and 3) were not altered by 12 months of daily recombinant hGH treatment. In summary, a specific antiserum and RIA were used to demonstrate elevated levels of intact IGF-II-binding IGFBP-6 in serum of CRF children. We postulate that the excess IGFBP-6 may modulate the action of IGF-II on target tissues.

Reduced concentration of serum growth hormone (GH)-binding protein in children with chronic renal failure: correlation with GH insensitivity. The European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood. The German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

Growth retardation in children with chronic renal failure (CRF) despite normal or elevated GH levels indicates a peripheral insensitivity to the action of GH. One possible molecular mechanism is a reduced density of GH receptors in GH target organs. In humans, the circulating high affinity GH binding protein (GHBP) is thought to reflect GH receptor expression, because it is derived from the extra-cellular domain of the GH receptor by proteolytic cleavage. We, therefore, analyzed serum GHBP levels by ligand-mediated immunofunctional assay in 126 children with CRF compared to reference values obtained by analysis of 773 healthy children. In 77% of CRF patients, serum GHBP concentrations were below the mean for age- and gender-matched controls. The decrease in serum GHBP levels was related to the degree of renal dysfunction. In advanced CRF (glomerular filtration rate, < 35 mL/min.1.73 m2), mean age- and gender-adjusted GHBP levels were -1.40 +/- 0.18 SD score; 36% of patients had GHBP levels below the normal range (< -2 SD score). Children with end-stage renal disease (n = 26) had the lowest GHBP levels (-2.25 +/- 0.22 SD score). Multiple linear regression analysis revealed that body mass index, rather than glomerular filtration rate, is the prevailing determinant of serum GHBP levels in CRF. GHBP levels correlated with both the spontaneous growth rate ( r = 0.44; P < 0.0001) and the growth response to GH therapy (r = 0.48; P < 0.005), indicating decreased sensitivity to both endogenous and exogenous GH. Subcutaneous GH therapy did not consistently affect serum GHBP levels after 3 months of treatment. It is suggested that low GHBP levels in children with CRF represent a quantitative tissue GH receptor deficiency as one of the molecular mechanisms of GH insensitivity.