The diagnostic terms hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are based on historical and overlapping clinical descriptions. Advances in understanding some of the causes of the syndrome now permit many patients to be classified according to etiology. The increased precision of a diagnosis based on causation is important for considering logical approaches to treatment and prognosis. It is also essential for research. We propose a classification that accommodates both a current understanding of causation (level 1) and clinical association in cases for whom cause of disease is unclear (level 2). We tested the classification in a pediatric disease registry of HUS. The revised classification is a stimulus to comprehensive investigation of all cases of HUS and TTP and is expected to increase the proportion of cases in whom a level 1 etiological diagnosis is confirmed.

This study identified an association between the use of plasma treatment and poor long-term outcome and confirms already known risk factors for poor prognosis. Follow-up investigations for at least 5 years are recommended to detect late-emerging sequelae.

In this functional magnetic resonance imaging study, 17 children were asked to make numerical and physical magnitude classifications while ignoring the other stimulus dimension (number-size interference task). Digit pairs were either incongruent (3 8) or neutral (3 8). Generally, numerical magnitude interferes with font size (congruity effect). Moreover, relative to numerically adjacent digits far ones yield quicker responses (distance effect). Behaviourally, robust distance and congruity effects were observed in both tasks. Imaging baseline contrasts revealed activations in frontal, parietal, occipital and cerebellar areas bilaterally. Different from results usually reported for adults, smaller distances activated frontal, but not (intra-)parietal areas in children. Congruity effects became significant only in physical comparisons. Thus, even with comparable behavioural performance, cerebral activation patterns may differ substantially between children and adults.

Summary:The aim of this prospective study was to assess glomerular and tubular renal function before, and 1 and 2 years after hematological stem cell therapy (HSCT) in children and adolescents. 137 consecutive patients undergoing HSCT, for malignant diseases, were included in a prospective trial. Forty-four patients were followed for up to 1 year after HSCT and 36 for up to 2 years, without relapse. Ninety healthy school children were used as a control group. The following parameters were investigated: inulin clearance (GFR), urinary excretion of albumin, ␣ 1 -microglobulin (␣ 1 -MG), calcium, ␤-Nacetylglucosaminidase (␤-NAG) and Tamm-Horsfall protein (THP), tubular phosphate reabsorption (TP/Cl cr ) and percent reabsorption of amino acids (TAA). Significantly lower GFR was found 1 and 2 years after HSCT but within the normal range in the period before HSCT. There was no correlation between GFR within the first month after HSCT and long-term outcome of GFR. Tubular dysfunction was found in 14-45% of patients 1 and 2 years after HSCT depending on the parameter investigated. Pathological values 1 and 2 years after HSCT were found for ␣ 1 -MG excretion in 40% and 39%, respectively, for TP/Cl cr in 44% and 45%, for ␤-NAG in 26% and 19%. Median TP/Cl cr was significantly lower 2 years after HSCT than before. TAA was mildly impaired in 7/14 patients before, in 5/29 one and in 9/29 2 years after HSCT, but median TAA was within normal range at all times. The median excretion of albumin, THP and calcium was within the normal range at all investigations. No influence of ifosfamide pre-treatment on the severity of tubulopathy was found. The investigation of tubular renal function should be part of a long-term follow-up in children after HSCT. Bone Marrow Transplantation (2001) 27, 319-327.

AIM The aim of this study was to determine the influence of chronic monotherapy with antiepileptic drugs (AEDs) on vitamin D levels, bone metabolism, and body composition.METHOD Eighty-five children (38 males, 47 females; mean age 12y 5mo, SD 3y 4mo) were treated with valproate and 40 children (28 males, 12 females; mean age 11y 10mo, SD 3y) were treated with other AEDs (lamotrigine, sulthiame, or oxcarbazepine), comprising the non-valproate group. Forty-one healthy children (29 males 12 females; mean age 12y 1mo, SD 3y 5mo) served as a comparison group. Height, weight, body impedance analysis, 25-hydroxyvitamin D, calcium, phosphate, two bone resorption markers (receptor activator of nuclear factor jB ligand [RANKL] and tartrate-resistant acid phosphatase 5b [TRAP5b]), osteoprotegerin, and leptin were measured. RESULTS No child was vitamin D deficient as defined by a 25-hydroxyvitamin D (25OHD) level ofless than 25nmol ⁄ l (<10ng ⁄ ml). Leptin, body fat, weight standard deviation score (SDS), and body mass index (BMI) SDS were all significantly higher (each p<0.001) in valproate-treated children than in the non-valproate group, as were calcium (p=0.027) and RANKL (p=0.007) concentrations. Similarly, leptin was significantly higher in the valproate group than in control participants (p<0.001), as were body fat (p=0.023), weight SDS (p=0.046), BMI SDS (p=0.047), calcium (p<0.001), and RANKL (p<0.001), whereas TRAP5b concentrations were significantly lower in the valproate-treated group (p=0.002). Furthermore, calcium and RANKL levels were significantly higher in the non-valproate group than in comparison participants (p<0.001 and p=0.016 respectively).INTERPRETATION Non-enzyme-inducing or minimal enzyme-inducing AED monotherapy does not cause vitamin D deficiency in otherwise healthy children with epilepsy. Valproate therapy is associated with increases in weight, body fat, and leptin concentration, as well as with a bone metabolic profile that resembles slightly increased parathyroid hormone action.Chronic antiepileptic drug (AED) therapy has been associated with vitamin D deficiency, low bone mass, increased fracture risk, and altered bone turnover.1 The underlying pathophysiological mechanisms are poorly understood but are probably multifactorial. Most older AEDs (e.g. phenobarbital, phenytoin, and carbamazepine) are strong cytochrome P450 (CYP450) enzyme inducers, thereby causing altered steroid and vitamin D metabolism, whereas valproic acid (valproate) and the newer AEDs such as lamotrigine and oxcarbazepine are non-enzyme inducers or minimal enzyme inducers. Some, but not all, studies in adults treated with new AEDs have observed vitamin D deficiency (as defined by a 25-hydroxyvitamin D [25OHD] level <25nmol ⁄ l [<10ng ⁄ ml]) and low bone mineral density (BMD).2-4 Studies on the effect of chronic AED therapy on bone metabolism in children have produced conflicting results. Valproate monotherapy was first reported to reduce BMD in children. 5 Since then, most studies have failed to demonstrate low bone ma...