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Damage to nonmotor dopamine (DA)-mediated frontostriatal circuits has been proposed as the main pathophysiological basis of cognitive dysfunction in Parkinson's disease (PD). In the present study, 18 early nondemented drug naive PD patients were investigated, by dual-tracer N-ω-fluoropropyl-2β-carbomethoxy-3β-4-[123I]iodophenyl-nortropane ([123I]FP-CIT) single-photon emission computed tomography (SPECT)/[18F] fluoro-deoxyglucose (FDG) positron emission tomography (PET) imaging, to test whether an early and not yet treatment-modulated relation exists between cognitive functions, caudate nucleus (CN) DA impairment and brain metabolism (CMRglc) in associative frontostriatal circuits. Verbal fluency performance correlated with DA impairment in CN, and with CMRglc in dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). Further, CMRglc in orbitofrontal cortex, DLPFC, and ACC was shown to be early modulated by the level of DA impairment in CN. The present study demonstrates in vivo the early functional disruption of nonmotor frontostriatal circuits in PD. The effect of CN DA impairment on DLPFC and ACC metabolism is proposed as a possible early pathophysiological and functional substrate for executive dysfunction in PD., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Although pediatricians are frequently confronted with patients presenting urolithiasis symptoms without obvious stones, the syndrome of occult urolithiasis may be still viewed with some skepticism. We have compared the clinical and metabolic features of 197 children with obvious calculi, 189 with microcalculi (diameter ≤ 3 mm based on renal sonography), and 114 with symptoms of urolithiasis and normal renal sonography findings. Only microcalculi and normal sonography subjects with a urinary abnormality potentially leading to urolithiasis were included in the study. Age at presentation increased significantly (p = 0.0001) in the groups in the order normal sonography to microcalculi to calculi groups. There was no significant difference among the three groups in terms of family history of urolithiasis, gender distribution, and degree of hypercalciuria, hyperuricosuria, hyperoxaluria, or hypocitraturia. The average frequency of pain attacks of patients with recurrent abdominal pain (RAP) ranged from 3.6 to 4.6 days of pain per month among the three groups, which is four to ninefold lower than that reported for children with functional or organic gastrointestinal RAP. The consistency of many clinical and urinary metabolic characteristics indicates a common underlying disorder in overt and occult urolithiasis. The increase of age at presentation from the normal sonography to microcalculi and calculi groups may reflect progressive crystal accretion leading ultimately to overt stone formation.

Courtship behaviours are common features of animal species that reproduce sexually. Typically, males are involved in courting females. Insects display an astonishing variety of courtship strategies primarily based on innate stereotyped responses to various external stimuli. In Drosophila melanogaster, male courtship requires proteins encoded by the fruitless (fru) gene that are produced in different sex-specific isoforms via alternative splicing. Drosophila mutant flies with loss-of-function alleles of the fru gene exhibit blocked male courtship behaviour. However, various individual steps in the courtship ritual are disrupted in fly strains carrying different fru alleles. These findings suggest that fru is required for specific steps in courtship. In distantly related insect species, various fru paralogues were isolated, which shows conservation of sex-specific alternative splicing and protein expression in neural tissues and suggests an evolutionary functional conservation of fru in the control of male-specific courtship behaviour. In this review, we report the seminal findings regarding the fru gene, its splicing regulation and evolution in insects.

Purpose: The aim of the present study was to evaluate the reciprocal relationships between motor impairment, dopaminergic dysfunction, and cerebral metabolism (rCMRglc) in de novo Parkinson's disease (PD) patients., Methods: Twenty-six de novo untreated PD patients were scanned with (123)I-FP-CIT SPECT and (18)F-FDG PET. The dopaminergic impairment was measured with putaminal (123)I-FP-CIT binding potential (BP), estimated with two different techniques: an iterative reconstruction algorithm (BP(OSEM)) and the least-squares (LS) method (BP(LS)). Statistical parametric mapping (SPM) multiple regression analyses were performed to determine the specific brain regions in which UPDRS III scores and putaminal BP values correlated with rCMRglc., Results: The SPM results showed a negative correlation between UPDRS III and rCMRglc in premotor cortex, and a positive correlation between BP(OSEM) and rCMRglc in premotor and dorsolateral prefrontal cortex, not surviving at multiple comparison correction. Instead, there was a positive significant correlation between putaminal BP(LS) and rCMRglc in premotor, dorsolateral prefrontal, anterior prefrontal, and orbitofrontal cortex (p < 0.05, corrected for multiple comparison)., Conclusions: Putaminal BP(LS) is an efficient parameter for exploring the correlations between PD severity and rCMRglc cortical changes. The correlation between dopaminergic degeneration and rCMRglc in several prefrontal regions likely represents the cortical functional correlate of the dysfunction in the motor basal ganglia-cortical circuit in PD. This finding suggests focusing on the metabolic course of these areas to follow PD progression and to analyze treatment effects.

The SLIT2 receptor ROBO2 plays a key role in the formation of the ureteric bud, and its inactivation in mice leads to supernumerary ureteric bud development, lack of ureter remodeling, and improper insertion of the ureters into the bladder. Recently, two heterozygous ROBO2 missense mutations were identified in two families with primary vesicoureteral reflux occurring in combination with congenital anomalies of the kidney and urinary tract (VUR/CAKUT). This study investigated a possible causal role of ROBO2 gene variants in 95 unrelated patients with primary VUR (n = 78) or VUR/CAKUT. Eighty-two percent of all patients had a family history of genitourinary anomalies. Twenty-four ROBO2 gene variants were identified by direct sequencing of all 26 exons and the exon-intron boundaries. Of these, four led to amino acid substitutions: Gly328Ser, Asn515Ile, Asp766Gly, and Arg797Gln. When the families were examined, the missense variants co-segregated with VUR (three families) or VUR/CAKUT (one family). These variants were not found in 190 control subjects, and the affected amino acids have been conserved through evolution. In conclusion, a relatively high frequency of ROBO2 variants (5.1%) was found in familial cases; however, functional studies and validation in other cohorts are warranted.

Objective: To estimate dietary protein intake in children with idiopathic hypercalciuria (HC) and/or hyperuricosuria (HU)., Patients and Methods: We compared the 24-h urinary excretion of urea, as a reflection of protein intake, in four age- and sex-matched groups, each comprising 56 consecutive children: (1) HC, (2) HU, (3) HC+HU and (4) control., Results: Urinary urea excretion was significantly higher in HC, HU and HC+HU than in controls. HC and HU children had similar urea excretion. HC+HU children had urinary urea significantly higher than HC and HU, but urinary calcium similar to HC and urinary uric acid excretion similar to HU subjects. Urinary calcium was significantly (R(2)=0.21) correlated with urea excretion in HC children only, whereas urinary uric acid was significantly (R(2)=0.21) correlated with urinary urea in HU children only. No significant correlation between urinary urea and calcium or uric acid excretion was found in HC+HU patients although they had the highest urinary urea. A significant (p=0.004) interaction between urinary urea and sodium in increasing urinary calcium excretion resulted only in the HC group., Conclusion: The association of dietary protein excess with HC and/or HU is conditioned by an individual (genetic?) predisposition and may be produced by different mechanisms.

In the tephritids Ceratitis capitata and Bactrocera oleae, the gene transformer acts as the memory device for sex determination, via an auto-regulatory function; and functional Tra protein is produced only in females. This paper investigates the evolution of the gene tra, which was characterised in twelve tephritid species belonging to the less extensively analysed genus Anastrepha. Our study provided the following major conclusions. Firstly, the memory device mechanism used by this gene in sex determination in tephritids likely existed in the common ancestor of the Ceratitis, Bactrocera and Anastrepha phylogenetic lineages. This mechanism would represent the ancestral state with respect to the extant cascade seen in the more evolved Drosophila lineage. Secondly, Transformer2-specific binding intronic splicing silencer sites were found in the splicing regulatory region of transformer but not in doublesex pre-mRNAs in these tephritids. Thus, these sites probably provide the discriminating feature for the putative dual splicing activity of the Tra-Tra2 complex in tephritids. It acts as a splicing activator in dsx pre-mRNA splicing (its binding to the female-specific exon promotes the inclusion of this exon into the mature mRNA), and as a splicing inhibitor in tra pre-mRNA splicing (its binding to the male-specific exons prevents the inclusion of these exons into the mature mRNA). Further, a highly conserved region was found in the specific amino-terminal region of the tephritid Tra protein that might be involved in Tra auto-regulatory function and hence in its repressive splicing behaviour. Finally, the Tra proteins conserved the SR dipeptides, which are essential for Tra functionality.

Purpose: We determined the long-term evolution of renal damage associated with vesicoureteral reflux., Materials and Methods: We retrospectively selected 74 consecutive children with unilateral primary vesicoureteral reflux, ipsilateral renal differential uptake less than 45% at dimercapto-succinic acid scintigraphy performed 4 to 6 months after urinary tract infection (60 patients) or shortly after diagnosis of vesicoureteral reflux investigated for prenatal hydronephrosis (14), and normal ultrasound and scintigraphic imaging of the contralateral nonrefluxing kidney. Average patient age at diagnosis was 3 years. The outcome was assessed via dimercapto-succinic acid scan at 5 to 24 years (mean 8.9)., Results: In 65 patients (88%) variations of less than 5% in differential uptake were recorded. Three patients (4%) showed an increase of greater than 5% in differential uptake of the refluxing kidney. Six patients (8%) demonstrated a decrease of greater than 5%, of whom 3 had 1 and 3 had no febrile urinary tract infection during followup. A total of 18 patients had a differential uptake of 35% to 45% at the first visit, of whom 3 exhibited a decrease of 5.2% to 27% in differential uptake and had no history of febrile urinary tract infection., Conclusions: In most cases differential uptake of the unilaterally refluxing affected kidney remains stable from early childhood to puberty despite the increase in body mass, which necessitates increasing renal work. In some patients a significant decrease in differential uptake may be observed even in the absence of recurrent febrile urinary tract infections. A mild decrease in differential uptake (35% to 45%) at diagnosis does not exclude the possibility of a subsequent significant decrease, even in the absence of febrile urinary tract infection.

Objective: In adults, it is well known that high protein intake may increase the risk of nephrolithiasis through increased urinary calcium excretion and other mechanisms. We aimed to assess the role of protein intake on urinary calcium excretion in children with idiopathic hypercalciuria (HC)., Patients and Methods: The 24-h urinary urea excretion as a reflection of protein intake was evaluated in 65 children with HC and in 76 normocalciuric control children. All of them were on a free diet and did not receive any specific drug., Results: Urinary urea excretion was 18.9+/-6.6 (SD) mmol/kg/day in the HC group and 14.2+/-4.9 in controls (P<0.0001). Urinary urea excretion significantly decreased with age, as well as with body weight and height gain in both groups. Calcium excretion significantly increased with increasing sodium and urea excretion in the HC but not the control group. There was a significant (P=0.005) interaction between urinary sodium and urea excretion in the rising calciuria of the HC group. Multiple regression analysis showed that, in the HC group, variations in urinary urea explained 11.4% of the entire variability of urinary calcium excretion, whereas adding the urinary sodium effect increased this relation only to 16%., Conclusion: Children with HC have a higher dietary protein intake than normocalciuric children. The decrease in urea excretion with increasing age and body mass may reflect the relatively higher protein intake of young growing individuals. Salt and protein have a cumulative effect on rising calcium excretion in HC children, but the role of protein intake is outstanding.

The finding of scintigraphic renal defects in children with febrile urinary tract infection (UTI) even in the absence of vesicoureteric reflux (VUR) has led to the conclusion that VUR is a weak predictor of renal defects in these patients. We used isotopic cystography (IC) for diagnosis of VUR in children with febrile UTI. Dimercaptosuccinic acid renal scintigraphy was performed 6 months after cure of the last UTI. Renal defects were defined by the finding of focal defects of radionuclide uptake and/or by a split renal function <43%. The study included 206 children with primary VUR and 77 without VUR. Among the subjects with and without VUR, respectively, renal defects were found in 40 and 6% (p=0.0001), focal uptake defects in 33 and 5% (p=0.0001) and split renal function <43% in 26 and 5% (p=0.0001). Permanent renal defects in children with febrile UTI are closely associated with VUR. The possibility that a child will have permanent renal defects can reasonably be ruled out on the basis of the absence of VUR by IC.

Aim: In children with recurrent abdominal pain (RAP), the location of pain to the flank may suggest the involvement of the urinary apparatus. We aimed to evaluate the location of pain in different age groups of children with idiopathic hypercalciuria (HC) and/or hyperuricosuria (HU) and RAP., Methods: Location of pain was assessed in 180 consecutive HC/HU children with RAP, aged 3-17.6 y, presenting to a single centre., Results: Considering four age groups, central/diffuse was more prevalent than lateral location of pain in youngsters, with a progressive and significant (p<0.0001, chi2 test for trend) decrease of the prevalence of central/diffuse location with rising age, and with the most relevant drop after age 8 y. Location of pain was central/diffuse in 81% of patients under and lateral in 79% of those over 8 y of age (p<0.0001). The location of pain changed from central/diffuse to lateral in 16/18 children followed at least 1 y, within 1 to 2 y by age 8., Conclusion: Only after 8 y of age did the lateral location of abdominal pain become the rule in children with HC/HU and RAP. This has to be kept in mind in order to avoid overlooking the urologic origin of pain.

Recurrent abdominal pains (RAPs) represent a common problem in children sometimes leading to unnecessary and invasive procedures. The rates of appendectomy were evaluated consecutively in 180 children with idiopathic hypercalciuria (HC) and/or hyperuricosuria (HU) and RAPs, and in 270 control subjects. Of the HC/HU patients 10% and of controls 1.5% underwent appendectomy (p<0.0001). In 15 out of 18 HC/HU patients appendectomized, RAPs persisted with the same frequency and severity after the operation; 10 out of 18 had dysuria and/or gross hematuria 2 days-12 months after appendectomy. At our first visit, urinalysis was negative for hematuria in 13 out of 18 patients and in eight out of the 10 with a previous history of dysuria or gross hematuria. Pain recurrences resolved or improved in nine out of the 11 patients followed at least 1 year after general or specific therapy for HC/HU. The inconstant association of dysuria and hematuria with RAPs in children with HC/HU may lead to the urological origin of pain being overlooked, and may explain the high rate of appendectomy among these children. The possibility of HC/HU therefore should be taken into account in children with RAPs even when dysuria and hematuria are not present.

Sports hematuria has been described in adult athletes. We report on two boys with gross hematuria after soccer matches. Urinalysis was negative for hematuria at the first visit. A simple test of effort provoked the phenomenon and allowed the detection of the post-renal origin of bleeding and the rapid resolution of hematuria. Such a test may be particularly helpful after the first episode, when it is problematic to postulate a cause-effect relationship between exercise and hematuria on the basis of the patients' history.

Background: Steatosis significantly contributes to an organ's transplantability. Livers with >30% fat content have a 25% chance of developing primary non-function (PNF). The current practice of evaluating a hematoxylin and eosin (H&E) stained donor biopsy by visual interpretation is subjective. We hypothesized that H&E staining of frozen sections fails to accurately estimate the degree of steatosis present within a given liver biopsy. To address this problem of evaluating steatosis in prospective donor organs, we developed a fast, user friendly computer methodology to objectively assess fat content based on the differential quantification of color pixels in Oil Red O (ORO) stained liver biopsies., Methods: The accuracy of human visual estimation of fat content by H&E and ORO stains was compared with computer-based measurements of the same slides from 25 frozen sections of donor biopsies., Results: Samples with a fat content >20% showed marked variation between human interpretation and computer analysis. There was also a significant difference in the human interpretation of fat based on the method of staining. This difference ranged from 3 to 37% with H&E., Discussion: Use of ORO resulted in a more consistent estimation of liver steatosis compared with H&E, but human interpretations failed to correlate with computer measurements. Such differences in fat content estimations might result in the rejection of a potentially transplantable organ or the acceptance of a marginal one. Ideally, our protocol can rapidly be applied to clinical practice for accurate and consistent measurement of fat in liver sections for the ultimate purpose of increasing the number of successful transplantable organs.

Steatotic mice are particularly susceptible to hepatic ischemia/reperfusion injury compared with their lean littermates. We have previously demonstrated that livers of mice having a spontaneous mutation in the leptin gene (ob/ob), resulting in global obesity and liver steatosis, are ATP depleted, are endotoxin sensitive, and do not survive (I/R) injury. We hypothesize that administration of an anti-LPS monoclonal antibody (mAb) prior to initiation of I/R would be protective from that insult. Steatotic mice (ob/ob) were subjected to 15 min of ischemia via complete porta-hepatis occlusion and varying lengths of reperfusion with or without pre-treatment with an anti-LPS mAb. There was 14-31% survival of isotype matched control mAb treated ob/ob mice after 15 min of ischemia and 24 h of reperfusion. In contrast, 75-83% of ob/ob mice pre-treated with an anti-LPS mAb prior to initiation of I/R survived both ischemia and 24 h of reperfusion. Furthermore, there was a decrease in ALT and circulating endotoxin levels when treated with an anti-LPS mAb compared with control antibodies. Attenuation of the endotoxin load with anti-LPS mAb, prior to initiation of I/R, was cytoprotective and improved survival. Consequently, these studies might offer a solution to the problems associated with using steatotic livers in clinical transplantation.

The number of patients requiring organ transplants still outpaces the number of available transplantable organs. During the process of orthotopic liver transplantation (OLTx), donor organs undergo significant stress resulting from ischemia and reperfusion. Healthy organs respond to this stressful environment with compensatory mechanisms that ideally allow for complete recovery. However, "marginal" organs do not compensate as well. Hepatic steatosis typically renders an organ nontransplantable; a liver with 30% or more fat has a 25% chance of primary nonfunction (PNF) or graft failure after a technically sound operation. In this study, we report on the significant markers of cellular ultrastructural change in steatotic livers. These include glycogen content, mitochondrial swelling, and hepatocellular blebbing. The data disclosed here argue that further investigation of these factors in marginal organs subjected to I/R may better facilitate our understanding of PNF.

Cerulenin has been shown to reduce body weight and hepatic steatosis in murine models of obesity by inhibiting fatty acid synthase (FAS). We have shown that attenuating intrahepatocyte lipid content diminished the sensitivity of ob/ob mice to ischemia/reperfusion injury and improved survival after liver transplantation. The mechanism of action is by inhibition of fatty acid metabolism by downregulating PPARalpha, as well as mitochondrial uncoupling protein 2 (UCP2), with a concomitant increase in ATP. A short treatment course of cerulenin prior to I/R injury is ideal for protection of steatotic livers. Cerulenin opens the potential for expanding the use of steatotic livers in transplantation., (Copyright 2004 Blackwell Munksgaard)

Growth retardation and osteopenia have been reported in some children with idiopathic hypercalciuria (IHC), particularly in those with nephrocalcinosis. The duration of hypercalciuria might be a risk factor for osteopenia. A retrospective longitudinal analysis of statural growth and a cross-sectional evaluation of bone mineral density (BMD) was carried out in 26 IHC children followed for 4-13 years. None of the patients had nephrocalcinosis. Growth, including pubertal growth spurt, was normal in all subjects. BMD Z score less than -1 was recorded in 3 subjects with hyperuricosuria. BMD Z score averaged -0.68+/-0.99 in the 9 subjects with associated hyperuricosuria and 0.21+/-0.64 in the 17 with occasional or no hyperuricosuria ( P=0.018). Our analysis shows that children with long-lasting IHC without nephrocalcinosis have normal growth, but those with associated hyperuricosuria may be at risk for osteopenia.

Background: Ultrasonic wave propagation in human tissues is not linear. As a consequence, harmonic waves, whose frequency is a multiple (harmonic) of the emitted frequency, are generated. Tissue Harmonic Imaging (THI) processes only the second harmonic frequency in order to improve the signal-to-noise ratio of the received signal. The study was aimed at investigating the impact of THI on the detection of the Left Ventricular (LV) endocardial border. Attention was paid to determine which LV walls were analysed more clearly with THI rather than with conventional Fundamental Frequency Imaging (FFI)., Methods: We compared the FFI and the THI visualization of the 16 LV segments and of the 6 LV walls in 30 consecutive patients by scoring the images as bad, sufficient or good. The equipment used was a GE Vingmed System Five (Orten, Norway)., Results: Images were good in 85% of segments explored with THI, whereas FFI provided good images in 47% of segments (p<0.001). From the apical window, visualization of the apex, lateral wall and anterior wall significantly improved with THI; using the parasternal approach, imaging of posterior wall was definitely better with THI than with FFI., Conclusions: THI enhances both endocardial visualization and global image quality. Tech-nical development, however, increases the diagnostic possibilities of echocardiography but does not substitute the operator's experience.

The medfly Ceratitis capitata contains a gene (Cctra) with structural and functional homology to the Drosophila melanogaster sex-determining gene transformer (tra). Similar to tra in Drosophila, Cctra is regulated by alternative splicing such that only females can encode a full-length protein. In contrast to Drosophila, however, where tra is a subordinate target of Sex-lethal (Sxl), Cctra seems to initiate an autoregulatory mechanism in XX embryos that provides continuous tra female-specific function and act as a cellular memory maintaining the female pathway. Indeed, a transient interference with Cctra expression in XX embryos by RNAi treatment can cause complete sexual transformation of both germline and soma in adult flies, resulting in a fertile male XX phenotype. The male pathway seems to result when Cctra autoregulation is prevented and instead splice variants with truncated open reading frames are produced. We propose that this repression is achieved by the Y-linked male-determining factor (M).

Background: An increased spot urine Na/K ratio (UNa/K) has been found to be related to urinary stone disease in adults with a history of nephrolithiasis and in children with idiopathic hypercalciuria (HC). However, the respective role played by Na and K excretion in the rise of the UNa/K in growing individuals is not well clarified., Methods: The urinary excretion of Na and K was evaluated in fasting morning and 24-hour urine samples of 37 consecutive children with HC and of 21 previously HC children who were normocalciuric at the time of the study (ExHC). None of them had received any dietary or specific drug prescription., Results: In the HC and in the ExHC group, respectively, the Na excretion was 4 +/- (SD) 2.4 and 2.9 +/- 1.3 mmol/kg/day (p = 0.009); the K excretion was 1.1 +/- 0.4 and 1.2 +/- 0.7 mmol/kg/day (p = 0.86); the fasting UNa/K was 3 +/- 1.6 and 2.1 +/- 1 mmol/mmol (p = 0.044), and the 24-hour UNa/K was 4.2 +/- 3.9 and 2.8 +/- 1.5 mmol/ mmol (p = 0.045). The 24-hour UNa/K was significantly higher than the fasting UNa/K in both HC (p = 0.002) and ExHC (p = 0.002) subjects. The 24-hour UNa/K significantly increased with age in both HC (p = 0.02) and ExHC (p = 0.015) children. The K excretion significantly decreased with age in HC (p = 0.0001) and ExHC (p = 0.005) subjects, as well as with body weight gain in HC (p = 0.005) and ExHC (p = 0.0001) children and with increasing body height in HC (p = 0.006) and ExHC (p = 0.001) subjects. In neither group was the K excretion significantly related to body mass index Z score nor to height Z score. No significant relation resulted between Na excretion and age, body weight and height, and body mass index Z score and height Z score., Conclusions: HC children have a higher Na excretion as well as a higher fasting and 24-hour UNa/K than ExHC children, but no different K excretion. Meals are accompanied by a significant rise in UNa/K. The rise in UNa/K with age is mostly due to a decrease in K excretion which possibly depends on childhood body growth., (Copyright 2002 S. Karger AG, Basel)

Objective: We assessed the risk for the occurrence of renal damage in children with vesicoureteric reflux (VUR)., Study Design: We reviewed the records of 187 consecutive children, aged 3.8 +/- (SD) 2.8 years, with unilateral primary VUR diagnosed after urinary tract infection (UTI). Dimercaptosuccinic acid renal scintigraphy was performed 4 to 6 months after the last UTI. Three patterns of renal damage were identified: global reduction (GR) of renal radionuclide uptake (20% to 40% of relative uptake), focal defects (FD) in uptake, and shrunken (relative uptake <20%) kidney (SK). We assumed that in these subjects FD indicated postpyelonephritic damage and that GR indicated congenital renal damage., Results: Scintigraphic renal damage of any type was present in 36.9% of the refluxing and in 3.2% of the nonrefluxing kidneys (odds ratio [OR], 17.6; 95% CI, 7.4 to 41.9). FD were present in 15.5% and 2.7% (OR, 6.7; CI, 2.5-17.6), GR in 19% and 0.5% (OR, 44.3; CI, 6.1 to 327.2), and SK in 6.9% and 0%, respectively. Patients with severe VUR showed a higher probability of renal damage than those with nonsevere VUR., Conclusions: In children with UTI and VUR, the refluxing kidney is most at risk of both congenital and acquired renal damage, and this risk increases with severity of reflux.

We compared the accuracy of isotope cystography (IC) and fluoroscopic cystourethrography (FC) in detecting vesicoureteric reflux (VUR) in children. FC and IC were performed in 124 children, 56 boys and 68 girls, aged 1 month to 9.2 years (mean 2.1 years), admitted consecutively for suspected VUR over a 10-month period. VUR was diagnosed by one or both studies in 51 of 124 (41%) patients. The two methods were concordant for the detection of VUR in 84% of kidney-ureter units and in 93% for the detection or exclusion of severe VUR. IC detected VUR more accurately than FC, both when all grades of VUR were considered together (P=0.00001) and when only severe reflux was considered (P=0.004). VUR was missed by FC in 23 of 51 (45%) subjects. Of those 23, 12 had severe VUR detected on one side at least by IC. VUR was missed by IC in 3 subjects. IC is significantly more accurate than FC in the initial diagnosis of VUR, even of severe grade. IC is the method of choice for the first diagnosis of VUR. Boys with VUR diagnosed by IC also need FC to investigate for posterior urethral valves.

Purpose: We distinguished the scintigraphy pattern of congenital reflux nephropathy from that of acquired scarring in children with primary vesicoureteral reflux., Materials and Methods: We retrospectively evaluated the frequency and pattern of renal scintigraphy abnormalities in 41 patients with prenatally detected primary vesicoureteral reflux and in 322 with a mean age plus or minus standard deviation of 3.6 + or - 1 years in whom primary reflux was detected after urinary tract infection. Dimercapto-succinic acid scintigraphy was performed 4 to 6 and 1 to 4 months after reflux was diagnosed and/or the infection was cured in patients with urinary tract infection and prenatal detection, respectively., Results: We identified 3 patterns of renal damage, including overall decreased uptake of renal radionuclide that was 20% to 40% of relative uptake, focal defects in uptake and shrunken kidney with relative uptake less than 20%. Scintigraphy revealed renal damage in 12 prenatally detected cases of vesicoureteral reflux, including overall decreased uptake in 58% and shrunken kidney in 42%, and in 111 cases of reflux detected at urinary tract infection, including overall decreased uptake in 50%, uptake focal defects in 37% and shrunken kidney in 13%. In the urinary tract infection group overall decreased uptake was present in 25 of 90 boys and in 40 of 232 girls (p = 0.05). Of these children 15% of the girls had uptake focal defects and 17% had overall decreased uptake. Overall decreased uptake and uptake focal defects were significantly more common in kidney-ureter units with reflux grade 4 or greater than in those with grade 3 or less (p = 0. 00001 and 0.027, respectively)., Conclusions: When assuming that overall decreased radionuclide uptake indicates congenital reflux nephropathy and uptake focal defects indicate postnatal acquired scarring, congenital reflux nephropathy appears to be an important cause of renal damage in children with primary vesicoureteral reflux even beyond the neonatal age and even in girls. This finding is of interest because postnatally acquired scarring may but congenital reflux nephropathy may not be prevented.

Body growth was studied in 32 subjects with vesicoureteric reflux (VUR), diagnosed following the prenatal finding of urinary tract dilatation, who had normal renal filtration function and who received antibacterial prophylaxis by the first few days of life. They were followed for 1-5 years (mean 2.3 years). Most had persistent VUR during the 1st year of life. Body growth performance was compared with that of 94 subjects with VUR diagnosed and treated by us after the neonatal period. During the follow-up period, none of the patients with prenatally detected VUR had a height Z score below -2, nor a weight-for-height index below 90%, and 1 had variations in height Z score >/=1. The difference in the percentage of patients with prenatally detected VUR (1/32) and those with VUR diagnosed and treated after the neonatal period (20/94) who had variations in height Z score >/=1 was significant (P=0.035). Patients with prenatally detected VUR and normal renal filtration function, given antibacterial prophylaxis by the first few days of life, have normal body growth, although VUR still persists.

Calyceal microlithiasis (CM) is characterized by the sonographic finding of hyperechogenic spots less than 3 mm in diameter in renal calyces, and it may be the first step in calculus formation. From January 1992 to January 1998, we have observed 216 children with CM. The present report deals with 34 of them in whom renal sonography was negative at first observation and the diagnosis of CM was made only on repeated sonographic examinations. The presenting symptoms were recurrent abdominal pain, dysuria, and hematuria occurring alone or in combination. Half of the patients had hypercalciuria. A history of urolithiasis in at least one first- or second-degree relative was present in 85% of patients. Renal sonography was repeated after 6-22 months (mean 11) and showed unilateral CM in 16 subjects and bilateral in 18. The finding of CM may be preceded by a period of time when symptoms and/or signs are present while microcalculi are not yet detectable. Repeated ultrasound examinations may be needed not only in patients with hypercalciuria but also in those with recurrent abdominal pain, dysuria, and/or hematuria not associated with hypercalciuria.

Statural growth to age > or = 20 years was studied in 10 boys with glomerulonephritis who received alternate-day prednisone (mean 1.2 mg/kg) for at least 2 consecutive years during pubertal age. Peak growth velocity was delayed after age 15 years in six patients and it was less than 7 cm/year in five. However, after age 16, growth velocity was significantly (p = 0.02) higher than expected and allowed patients to ultimately reach their genetic height potential.

Recognition of children at greatest risk for urolithiasis may allow early detection or prevention of stone formation. We report clinical data from 196 children aged 0.9-15.9 years in whom renal ultrasound examination revealed hyperechogenic spots in renal calyces less than 3 mm in diameter. We called this finding "calyceal microlithiasis" (CM). There was a history of urolithiasis in 70.4% of patients in at least one first- or second-degree relative. Presenting symptoms were recurrent abdominal pain, dysuria, and hematuria, occurring alone or in combination. Hematuria was the presenting symptom in 41% of patients and was the only urinary finding in more than one-third. Hypercalciuria was present in about one-third and hyperuricuria in one-fifth of the patients. Of 29 patients who were followed for at least 2 years, 9 developed calculi 4-7 mm in diameter. CM possibly represents the first step in calculus formation. The finding of CM might explain a number of symptoms and signs that are often mild and non-specific, thus reducing invasive diagnostic procedures.

An 8-year-old girl with systemic lupus erythematosus (SLE) and diffuse proliferative glomerulonephritis had chronic interstitial cystitis (CIC) early in the course of SLE. The early occurrence of CIC, the lack of intestinal symptoms, the association with vesicoureteric reflux, and the improvement of CIC during therapy with cyclosporin A were the prominent features of the patient reported here.

A longitudinal retrospective study of height Z score (HZ score) and weight-for-height index (WHI) was performed on 94 pre-pubertal children with vesico-ureteric reflux (VUR) and normal creatinine clearance followed for 1-6.8 years (mean 3.1 years). Thirty patients had bilateral VUR with scintigraphic signs of renal scarring (B+), 17 had bilateral VUR without renal scarring (B-), 27 had unilateral VUR with (U+) and 20 unilateral VUR without (U-) renal scarring. Thirty-three patients received only antimicrobial medication and 61 underwent successful antireflux operation. The increase in HZ score and WHI during the 1st year of follow-up was significantly (P = 0.001 and 0.00003, respectively) higher than during the 2nd year. At first visit, B+ subjects had an average WHI and HZ score that were significantly (P = 0.02 and 0.04, respectively) lower than the other groups of patients together. At last visit this difference was not significant. In B+ subjects, the WHI and HZ score at last visit were significantly (P = 0.04 for both) higher than at the first visit. B+ patients fully recover their body growth deficit compared with other groups of VUR subjects after medical and/or surgical therapy.

Height standard deviation scores (HSDS) and weight-for-height index (WHI) at diagnosis were evaluated in 156 children aged 2 months to 10.8 years (mean 3.7 years) with vesicoureteric reflux (VUR) and normal creatinine clearance, and in 156 age- and sex-matched healthy controls. Forty-three patients had bilateral VUR with scintigraphic signs of renal scarring (B SCAR+), 25 had bilateral VUR without renal scarring (B SCAR-); 40 had unilateral VUR with (U SCAR+) and 48 unilateral VUR without (U SCAR-) renal scarring. B SCAR+ patients had an average HSDS of -0.5 +/- 1.4 (SD) which was significantly (P = 0.02) below that of controls (0.05 +/- 1 HSDS) and an average WHI of 100.6% +/- 16% which was significantly (P = 0.007) below that of controls (108% +/- 12%); 14% of B SCAR+ patients had a height below -2 HSDS. B SCAR-, U SCAR+, and U SCAR- patients had heights near to O HSDS which was not different from that of controls, as well as WHI between 104% and 107.9%, which was not different from that of controls. HSDS and WHI were significantly (P = 0.00001) correlated in patients but not in controls. B SCAR-, U SCAR+, and U SCAR- patients are similar to healthy controls in weight and in height growth and have, on average, some excess weight as do the latter. In contrast, B SCAR+ subjects have a significant decrease of the relative height and normal WHI.

The pubertal growth spurt was followed for at least 3 years in 5 boys and 6 girls with chronic renal failure on conservative treatment. The peak height velocity averaged 8.6 cm/year (range 5.8-10.1 cm/year) in males and 8.2 cm/year (range 6.4-11.5 cm/year) in females. In none was the pubertal growth spurt below the 3rd percentile for chronological age. At the end of the follow-up period, all patients but 2 had stature within the normal limits of parental target. The relative variation of height averaged - 0.013 standard deviation scores per year. On the whole, the pubertal growth spurt was normal in subjects with chronic renal failure on conservative treatment.

Methods: Skeletal maturation was evaluated in 60 prepubertal children aged 7.7 +/- 0.27 years (range 2.7-12.6). The radius, ulna and short bones (RUS) and the carpal (CARP) bone age were assessed. Height corresponded to 1 +/- 0.1 Z scores., Results: RUS bone age was 1.04 +/- 0.2 years more advanced than chronological age (P = 0.0001). CARP bone age was only 0.2 +/- 0.2 years more advanced than chronological age and the difference was not significant. However, the degree of advancement of CARP bone age in respect of chronological age was significantly (P = 0.0001) correlated with height Z scores., Conclusions: CARP bone age is less sensitive than RUS bone age to the factors promoting the early skeletal maturation in obese children. Nevertheless, the degree of CARP bone age advancement, although minimal, is correlated with overheight.

Bone mineral content (BMC) was measured by single-photon absorptiometry in 24 children with steroid-dependent, minimal-lesion nephrotic syndrome after 1 to 6.3 years of alternate-day prednisone therapy and in a sex- and age-matched control group. Bone mineral content was -0.002 +/- 1.2 standard deviation scores in patients and 0.3 +/- 1.4 in controls (t = 1.17; P = 0.25). No significant relation was found between BMC in patients and the amount of prednisone taken or the duration of therapy. Alternate-day prednisone therapy at doses usually needed to keep children with steroid-dependent nephrotic syndrome under control does not significantly affect BMC.

Objectives: To distinguish the effects of juvenile rheumatoid arthritis (JRA) on bone mineralisation from those possibly caused by steroid therapy., Methods: Bone mineral status was evaluated in 20 children (five boys and 15 girls) with active JRA who never received steroids. Seven had oligoarticular, nine had polyarticular, and four had systemic JRA. Bone mineral content (BMC) was assessed by single beam photon absorptiometry and expressed as a Z score relative to normal values in healthy children. Serum calcium, phosphate, and alkaline phosphatase were measured by colorimetric methods. Whole parathyroid hormone was assayed by Immuno Radiometric Assay. Serum osteocalcin was measured by specific radioimmunoassay. Nutrient intake was assessed by a 24 hours dietary recall. BMC and nutrient intake were also assessed in an age and sex matched control group., Results: BMC was -1.5 (SEM 0.8) Z scores in patients and 0.4 (0.3) in the control group (p = 0.02). BMC averaged -4.9 (2) Z scores in the systemic JRA group, -1 (0.6) in the polyarticular group and 0.3 (0.7) in oligoarticular JRA patients. Serum calcium, phosphate and osteocalcin values were normal in all patients. No significant difference was found between JRA patients and controls in calcium, phosphate, energy, and protein intake., Conclusion: JRA subjects have significantly reduced BMC even in the absence of any steroid therapy. Bone demineralisation appears to depend more on disease activity and on reduced motility than on reduced nutrient intake.

Radius, ulna, short bones (RUS) and carpal (CARP) bone age were assessed in 26 steroid-dependent nephrotic boys after at least 1 year of alternate-day prednisone therapy, and in 26 age- and sex-matched control subjects. No significant difference in RUS bone age was found between patients and controls. CARP bone age of patients was significantly (P = 0.01) more retarded than in controls. In patients, CARP bone age delay was related to their relative height at the time of study (P = 0.01). We conclude that CARP bones are more prone to effects of steroids than are RUS bones. Therefore, CARP bone age may be a more sensitive tool in monitoring the effects of steroids on skeletal growth and maturation.

Vaccination against hepatitis B virus (HBV) was performed in 18 boys (aged 5.7 +/- 2.4 years) suffering from steroid-sensitive nephrotic syndrome (SSNS) and in a control group of 21 healthy boys (aged 5.6 +/- 3.8 years). The percentage of patients who responded to vaccination was significantly lower than the control group 1, 6, 8, 12, 18 and 24 months after the start of vaccination. The titre of antibodies to HBV surface antigen produced by responders at 6 and 24 months was significantly lower in patients than in the control group. Boys with SSNS have an impaired response to HBV vaccination.

Despite its potential advantages HDF has not gained large clinical acceptance among nephrologist due to its technical complexity and to the large quantity of pharmaceutical substitution fluid needed. HDF with on-line production of substitution fluid from dialysate simplifies the procedure and reduces the cost of treatment session. We treated regularly 13 high risk and/or non-compliant patients (9 males, 4 females) with HDF for 46 +/- 17 months. HDF program consisted of 3 sessions weekly lasting 210 +/- 10 mn with blood flow rate 350 +/- 20 ml/mn and fluid volume exchange of 20 liters/session. High flux dialyzers (HF80, Filtral 16) were reused 6 to 13 times automatically on a Renatron machine with peroxyacetic acid solution as sole cleaning and disinfecting agent. Microbiologic quality of infusate was assessed by membrane filtration culturing method and LAL endotoxin determination. 3937 HDF sessions were performed. 57.140 I of substitution fluid were infused IV to patients. Eight pyrogenic reactions were observed: 2 due to septicemia related to catheter infection and 6 from unknown origin. Adequacy of program was achieved in all patients. Blood pressure control was satisfactorily obtained without antihypertensive medication in 12/13 patients. Effective weekly integrated urea clearances was 150 +/- 15 l/wk, KT/V index was 1.50 +/- 0.10, urea TAC 20 +/- 2 mM/l and protein catabolic rate 1.40 +/- 0.10 g/kg/24 h. We conclude that HDF with on-line production of bicarbonate substitution fluid is a safe and highly efficient method cost-competitive with bicarbonate HD, which offers an interesting alternative for renal replacement therapy.

Statural growth was studied in 16 glomerulopathic children, 12 boys and 4 girls, treated with alternate-day prednisone for more than 2 years. Five patients were older than 12 years when started on therapy. Growth velocity was significantly slower in boys who received therapy during peripubertal age than in younger boys taking similar amounts of prednisone. In boys, pubertal growth spurt was delayed and shorter than normal, but growth continued with a velocity greater than normal for some years and kept on after 19 years of age. The ultimate height of the patients followed up after 19 years of age ranged within the normal limits of genetic height potential.

Anti-HBV vaccination was performed in 17 children with chronic renal insufficiency on conservative treatment and in 29 control children. The response to vaccination was satisfactory in patients as well as in the control group and no significant difference was found between the two groups as to percentage of responders and to the titre of HBsAb produced. It appears reasonable to vaccinate all patients with chronic renal insufficiency before they reach end-stage renal disease in areas with high prevalence of HBV infection.

The deterioration rate of creatinine clearance (CCr) was studied in 40 children with chronic renal failure (CRF) on conservative treatment followed up for at least 1 year (range 1-12). The deterioration rate of CCr was significantly (p less than 0.01) higher in glomerulopathies (G) than in hypoplasias (H) and in vascular nephropathies (VN) and significantly (p less than 0.01) higher in hereditary nephropathies (HN) than in VN. The differences in the deterioration rate of CCr between H and HN and between H and VN were not explainable on the basis of the different age at diagnosis or of the different prevalence of hypertension. These data indicate that the primary renal disease is important in determining the progression of CRF.

Twenty men and 23 women aged from 18 to 65 years, who had been under maintenance haemodialysis for 2 to 16 years and whose haematocrit had been below 30 percent for at least 3 months received recombinant human erythropoietin intravenously at the end of each session for one year. Anaemia was corrected in all patients, the delay in response to each dosage variation being about 4 weeks. The necessary maintenance dosage ranged from 96 to 240 u/kg/week. The number of leucocytes increased significantly until the 4th month, from 5880 +/- 1760 to 6600 +/- 1920 per cubic mm (P less than 0.01). During treatment, pre-dialysis blood creatinine concentrations and potassium and phosphate levels rose, while blood calcium levels fell significantly from 2.45 +/- 0.16 to 2.36 +/- 0.19 mmol/l (P less than 0.01). A nonsignificant increase in systolic and diastolic pressures was also observed, from 129 +/- 16 to 134 +/- 18 mmHg (P = 0.06) and from 75 +/- 9 to 78 +/- 10 mmHg (P = 0.07) respectively. Eight patients (18 percent) required antihypertensive drugs or a higher dose of those previously prescribed. There were 7 cases of vascular thrombosis on pre-existing stenosis, and the dosage of heparin during dialysis had to be increased in most patients. This study confirms that erythropoietin plays a major role in the genesis of the anaemia associated with renal failure. The absence of severe complications in this series was probably due to the criteria of inclusion in the study.

We report the first practical application of a genetic scheme devised for the purpose of obtaining large quantities of embryos of a specific sex. The scheme, which is based on the meiotic drive system Segregation Distorter, results in the production of populations of zygotes that are almost exclusively of one sex. We have used this scheme to determine that the steady-state levels of transcripts of X-linked genes are the same in early male and female embryos, establishing that these genes are dosage compensated.

To reduce the cost of hemodiafiltration (HDF), a standard hemodialysis machine was modified to permit in-line production of substitution fluid from bicarbonate dialysate. The authors' present data showing that this procedure was made bacteriologically safe; was simple to use, and offered a cheap approach to perform high-flux HDF using a hemodifilter of relatively small membrane surface area.

The concentration of plasma acetate, glucose, and ketone bodies were determined for both venous and arterial blood before and at the end of dialysis with an acetate-containing dialysate. We also determined lactate and pyruvate levels in arterial plasma. The results obtained in the same patients were compared when dialysis were done with or without glucose and discussed in terms of hormonal changes (insulin, glucagon). Arterial plasma acetate (p less than 0.001) and ketone body levels (p less than 0.05) increased significantly during dialysis both with glucose and without glucose (p less than 0.001 in both cases). Higher end-dialysis arterial levels were found for the latter set of glucose-free dialysis (p less than 0.05 and p less than 0.001, respectively, for acetate and ketone bodies), and a correlation was established between end-dialysis arterial concentrations of acetate and ketone bodies. This suggests high consumption of both endogenous and exogenous acetate to feed ketogenesis. This is concurrent with decreased insulin and high glucagon levels. Under these conditions, plasma accumulation of ketone bodies would facilitate an indirect elimination of acetate by the dialyzer (about 10% of the acetate load). Our results suggest that hormone variations during glucose-free dialysis which promote fatty acid oxidation and ketogenesis from acetyl groups hinder acetate-dependent lipogenesis.