Inadequate leptin level negatively affects body fat loss during a weight reduction programme for childhood obesity.

UNLABELLED: Obesity is a typical example of a complex multifactorial disease arising from behavioural, environmental and genetic factors that may affect individual responses to dietary intake and physical activity. Observational, longitudinal dietary interventional studies in obese patients present contrasting reports on the predictive value of baseline leptin levels. We report on the effect of a weight reduction programme in three different groups of obese children (82 patients in all) assembled on the basis of their baseline leptin levels adjusted for body mass index (BMI), gender and pubertal development. The effectiveness of this programme was decreased in patients with relative hyperleptinaemia or hypoleptinaemia compared to children with baseline leptin levels appropriate to BMI gender and pubertal development. CONCLUSION: Information gained from leptin assays could provide predictive insight into an individual's ability to lose body fat and may therefore have important implications for our approach to the treatment and prevention of childhood obesity.

Agonist-induced internalization and desensitization of the human nociceptin receptor expressed in CHO cells.

In this study, we examined agonist-induced internalization, recycling and signalling (measure of cAMP levels) of the cloned human nociceptin receptor (hNOP) expressed in CHO-K1 cells. Internalization was proven by a receptor-binding assay on viable cells. The agonist nociceptin/orphanin FQ (NC) promoted rapid internalization of the hNOP receptor (approximately 78% of cell surface receptors were lost after 2 min exposure to 1 microM NC) in a clathrin- and ATP-dependent manner. Internalization was more rapid and marked in CHO-K1 cells than, as we previously reported, in SK-N-BE cells. This difference may be related to higher levels of beta-arrestin isoforms detected in CHO-K1 than in SK-N-BE cells. hNOP receptor internalization was partially reversible and recycling occurred in the presence of the agonist; receptor recycling was dependent on okadaic acid-sensitive phosphatases and was blocked by monensin. Confocal microscopy analysis confirmed the internalization and the recycling back to the plasma membrane of an epitope-tagged hNOP receptor expressed in CHO-K1 cells. These receptors underwent rapid desensitization upon agonist challenge: NC efficacy in inhibiting forskolin-stimulated cAMP production was significantly reduced 10 min after exposure and correlated with the rate of receptor internalization. Moreover, we observed that blockade of hNOP receptor recycling by monensin would cause a more prolonged and relevant desensitization of this receptor. Thus, the dynamic cycle between hNOP receptor activation, internalization and recycling determines the activity of this receptor on the cell surface.

Nociceptin-induced internalization of the ORL1 receptor in human neuroblastoma cells.

Nociceptin/orphanin FQ (NC) has been proposed as endogenous ligand of the opioid receptor-like 1 (ORL1) receptor. We investigated NC-induced internalization and recycling of the ORL1 receptor in SK-N-BE human neuroblastoma cells. Internalization was proven by receptor binding assay on viable cells. NC promotes a time- and concentration-dependent internalization of the ORL1 receptor (57% of cell surface receptors are lost after 30 min exposure to 1 microM NC) in a clathrin- and ATP- dependent manner. After 30 min exposure to NC, ORL1 receptor internalization is partially reversible and recycling is dependent on acid phosphatases. Over-expression of beta-arrestin 2 increases NC-promoted internalization of the ORL1 receptor. These events contribute to NC signaling in neuronal cells through sequestration and recycling of the ORL1 receptor.

Mutational screening of the CART gene in obese children: identifying a mutation (Leu34Phe) associated with reduced resting energy expenditure and cosegregating with obesity phenotype in a large family.

Cocaine- and amphetamine-regulated transcript (CART) inhibits feeding and induces the expression of c-Fos in hypothalamic areas implicated in appetite regulation. Furthermore, the CART peptide is found in neurons regulating sympathetic outflow, which in turn play an integral role in regulating body temperature and energy expenditure. The CART gene was screened by single-strand conformation polymorphism and automatic sequencing in 130 (72 girls) unrelated obese Italian children and adolescents. Their Z-scores (mean +/- SD) of relative to BMI percentiles was 3.9 +/- 1.8, and the average age at obesity onset was 4.7 +/- 2.6 years. Two previously described silent polymorphisms were found in the 3' untranslated region: an adenine deletion at position 1457 in 9 patients (allele frequency 0.035) and an A/G substitution at position 1475 in 11 patients (allele frequency 0.042). We found no difference between the obese patients heterozygous for one of these polymorphisms and those patients homozygous for the wild allele with respect to their age of obesity onset, BMI Z-scores, and leptin levels. A missense mutation of G729C resulting in the substitution of Leu with Phe at codon 34, within the NH2-terminal CART region, has been detected in the heterozygous state in a 10-year-old obese boy who has been obese since the age of 2 years. The patient belongs to a large family of obese subjects. The mutation cosegregated with the severe obesity phenotype over three generations and was not found in the control population. Resting metabolic rates were lower than expected in the propositus (-14%) and his mother (-16%), who carried the mutation. Leucine at codon 34, conserved in this position in the human and in the rat sequences, immediately precedes a couple of lysine residues that may well represent a dibasic processing site. The Leu34Phe mutation might alter the susceptibility to proteolysis of this potential processing site, likely altering the CART effect on thermogenesis and energy expenditure.

Unilateral vesicoureteric reflux: Low prevalence of contralateral renal damage.

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.

Opioid peptides attenuate blood pressure increase in acute respiratory failure.

Plasma opioid peptides, norepinephrine, atrial natriuretic factor (ANF) and blood pressure (BP) were assessed in 24 chronic obstructive pulmonary disease patients with acute respiratory failure. Hypoxemic-hypercapnic patients had high BP, beta-endorphin, Met-enkephalin and dynorphin B, whereas hypoxemic-normocapnic and hypoxemic-hypocapnic patients showed normal BP, high beta-endorphin, and normal Met-enkephalin and dynorphin B. Norepinephrine and ANF were high in all patients, particularly in hypoxemic-hypercapnic patients. Infusion with the opioid antagonist naloxone hydrochloride significantly increased systolic blood pressure (SBP) in hypoxemic-hypercapnic (182.0 +/- 3.2 versus 205.1 +/- 3.0 mmHg; P < 0.01), hypoxemic-normocapnic (149.3 +/- 1.8 versus 169.1 +/- 2.2 mmHg; P < 0.01) and hypoxemic-hypocapnic (147.3 +/- 1.3 versus 166.8 +/- 2.2 mmHg; P < 0.01) patients, norepinephrine in hypoxemic-hypercapnic patients (3583.2 +/- 371.8 versus 5371.3 +/- 260.0 fmol/ml; P < 0.01), and reduced ANF in hypoxemic-normocapnic (18.3 +/- 0.8 versus 11.9 +/- 1.0 fmol/ml; P < 0.05) and hypoxemic-hypocapnic (18.1 +/- 1.2 versus 12.1 +/- 2.1 fmol/ml; P < 0.05) patients. These results indicate that the endogenous opioid system attenuates SBP responses in acute respiratory failure by affecting norepinephrine or ANF release.

Molecular screening of the proopiomelanocortin (POMC ) gene in Italian obese children: report of three new mutations.

BACKGROUND: Although linkage studies strongly suggest that proopiomelanocortin (POMC) alterations could play a role in the genetic predisposition to obesity, systematic POMC mutational analysis did not completely confirm this hypothesis. OBJECTIVES: To verify the presence of mutations of the POMC coding region in Italian children with very early onset obesity. SUBJECTS AND METHODS: Eighty seven unrelated Italian obese children and adolescents were studied. Mean age at obesity onset was 4.7+/-2.5 y. The POMC gene coding region was screened using single-strand conformation polymorphism (SSCP) analysis. Bi-directional automatic sequencing of PCR products was performed for all individuals who showed an aberrant SSCP pattern. RESULTS: Three new mutations have been identified in the heterozygous state in three patients: (a) G3834C, resulting in the substitution of Ser with Thr at codon 7 within the POMC signal peptide; (b) C3840T, resulting in the substitution of Ser with Leu at codon 9 of the pre-proopiomelanocortin signal peptide; and (c) C7406G, producing the substitution of Arg with Gly at codon 236 within the beta-endorphin peptide. A polymorphism consisting of a 9 bp insertion, AGC AGC CGC, between position 6997 and 6998 has been found at the heterozygous state in nine patients. They showed leptin levels adjusted for BMI, gender and pubertal stage significantly higher than obese subjects homozyous for the POMC wild-type allele. CONCLUSIONS: Mutations in codons 7 and 9 of the signal peptide may alter the translocation of the pre-proopiomelanocortin into the endoplasmic reticulum and, therefore, can be implicated in obesity. Although further studies are required, the polymorphism between position 6997 and 6998 may represent one of the genetic variations that explain the linkage between obesity and POMC. International Journal of Obesity (2001) 25, 61-67

Hyperuricosuria in children: clinical presentation and natural history.

OBJECTIVE: Idiopathic hyperuricosuria (HU) was previously reported in only a limited number of children with hematuria. We aimed to outline the clinical presentation and natural history of HU not only in children with hematuria, but also in those with dysuria and/or recurrent abdominal/flank pain and a family history of urolithiasis. STUDY DESIGN: Retrospective analysis of data at diagnosis from 102 consecutive children with HU and outcome analysis of 26 of them who were followed >/=1 years (mean: 3.1) with no specific therapy. RESULTS: Sixty-one participants had HU and 41 had HU + hypercalciuria. Fifty-two patients had no hematuria among the presenting symptoms, more than one third had normal urinalysis at our first examination, one half had microcalculi (<3 mm in diameter) at renal sonography, and 12% had stones (4-18 mm). Thirty participants of the 39 with no hematuria at our first examination (77%) showed microcalculi or calculi at renal sonography. The patients with microcalculi were significantly older than were those without microcalculi. During the follow-up, 4 of 26 children never had hematuria and 8 had no hematuria during most of the follow-up period. Two patients who had a calculus at first visit and 3 who formed calculi 4 to 12 mm in diameter, after 1 to 3.5 years subsequently passed them in the urine. CONCLUSIONS: The lack of hematuria is not predictive of absence of urolithiasis. Therefore, it may be misleading to judge on the efficacy of a given therapy only based on disappearance of hematuria. HU and hypercalciuria have to be suspected in children with dysuria and those with recurrent abdominal/flank pain and familial history of urolithiasis, although they have no hematuria.

Synthesis and binding affinity of cis-(-)- and cis-(+)-N-ethyleneamino-N-nordeoxymetazocine and cis-(-)-N-normetazocine analogues at sigma1, sigma2 and kappa opioid receptors.

The synthesis of cis-(+)- and cis-(-)-N-ethyleneamino-N-nordeoxymetazocine and cis-(-)-N-normetazocine analogues is described and their affinities to sigma1, sigma2 and kappa opioid receptors are evaluated. The cis-(+)-deoxy compounds displayed high sigma/kappa selectivity with nanomolar K(i) values for sigma1 receptors, whereas in the cis-(-)-N-normetazocine series the compound (-)-7b was found to bind with nanomolar affinity to the kappa opioid receptor (K(i)=21.5 nM). Compound (-)-7b showed good selectivity for the kappa opioid receptor in comparison to the sigma1 and sigma2 sites and to the mu and delta opioid receptors. A correlation of the binding affinities between cis-(-)- and cis-(+)-N-deoxynormetazocine derivatives show that both isomers of the deoxy analogs have similar sigma1 and sigma2 binding profiles as the cis-(+)-N-normetazocine derivatives.

Effects of specific bile acids on c-fos messenger RNA levels in human colon carcinoma Caco-2 cells.

Bile acids may play a role in the pathogenesis of intestinal inflammation by activating the signalling pathways that control cell proliferation, among other cell systems. We investigated the action of different bile acids, particularly chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), on steady-state and transcriptional regulation of the protooncogene c-fos, involved in the regulation of cell proliferation and differentiation, in colon carcinoma Caco-2 cells. Specific bile acids had a stimulatory effect of on the expression of c-fos mRNA. This proved to be concentration- and time-dependent and may be partly due to an increase in the rate of transcription of the corresponding gene rather than to any change in the stability of mRNA. In Caco-2 cells exposed to 250 microM CDCA for 1 h a maximal increase of c-fos mRNA ( approximately 2.5-fold induction over the control) was observed; deoxycholic acid (DCA; 250 microM) and lithocholic acid (LCA; 250 microM) were less effective (approximately 2-fold induction over the control). UDCA and cholic acid (CA) did not modify c-fos gene expression in this cell line. Finally, we investigated the role of protein kinase C (PKC) in transcriptional regulation of the c-fos gene by bile acids. Although induction of c-fos by 12-O-tetradecanoyl 13-acetate (10 nM), a potent PKC activator, was completely antagonised by bis-indolyl-maleimide I (1 microM); only about 40% of the bile acid-mediated rise in c-fos mRNA was blocked. Thus it appears that PKC, as well as other signalling pathways, is involved in CDCA-, DCA- and LCA-induced c-fos gene expression.

Idiopathic hypercalciuria and hyperuricosuria: family prevalence of nephrolithiasis.

We studied the prevalence of a history of nephrolithiasis in first- and second-degree relatives of 74 children with hypercalciuria (HC), 61 with hyperuricosuria (HU), and 41 with HC plus HU, and in a control population of 261 children with different diseases. Family history of nephrolithiasis was found in 69% of HC, 75% of HU, 78% of HC plus HU, and 22% of control patients. The prevalence was not different among HC, HU, and HC plus HU groups, but was significantly higher in each study group than the control group (P=0.0001). Body mass index >95th percentile was found in only 4.7% of the patients with HC or HC plus HU. Calculi (>3 mm in diameter) were present in 8.9% of the patients with a family history of nephrolithiasis and in 9.4% of those with no family history (P=0.85). Microcalculi (<3 mm in diameter) were found by sonography in 56.6% of the patients with and in 53.3% of those without a family history of nephrolithiasis (P=0.83). Children with HC and/or HU have a strong familial prevalence of nephrolithiasis. Obesity does not seem to affect the association of familial nephrolithiasis and hypercalciuria in children. The presence of nephrolithiasis in families of children with HC and/or HU is not associated with a higher rate of formation of calculi or microcalculi.

Enhanced detection of vesicoureteric reflux with isotopic cystography.

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.

Nonpeptide analogues of dynorphin A(1-8): design, synthesis, and pharmacological evaluation of kappa-selective agonists.

Two novel series of kappa opioid receptor agonist analogues of MPCB-GRRI and MPCB-RRI, hybrid ligands of MPCB ((-)-cis-N-(2-phenyl-2-carbomethoxy)cyclopropylmethyl-N-normetazocine ) and of the C-terminal fragments of dynorphin A(1-8), have been synthesized. The critical functional groups of the peptide fragments of hybrid compounds were maintained, and the binding affinities and selectivities for compounds 1-40 to mu, delta, and kappa opioid receptors were analyzed. Compounds 15 and 16, MPCB-Gly-Leu-NH-(CH(2))(n)()-NH-C(=NH)-C(4)H(9) (n = 5, 6), displayed high affinity and selectivity for kappa opioid receptors (K(i)(kappa) = 6.7 and 5.3 nM, K(i)(mu)/K(i)(kappa) = 375 and 408, and K(i)(delta)/K(i)(kappa) = 408 and 424, respectively). Since kappa agonists may also cause psychotomimetic effects by interaction with sigma sites, binding assays to sigma(1) sites were performed where compounds 15 and 16 showed negligible affinity (K(i) > 10 000). Compounds 15 and 16 were further characterized in vivo and showed potent antinociceptive activity in mouse abdominal constriction tests (ED(50) = 0.88 and 1.1 mg/kg, respectively), fully prevented by nor-BNI. Thus, these novel analogues open an exciting avenue for the design of peptidomimetics of dynorphin A(1-8).

High incidence of a generally small kidney and primary vesicoureteral reflux.

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.

Substituted 1-phenyl-2-cyclopropylmethylamines with high affinity and selectivity for sigma sites.

A series of 1-phenyl-2-cyclopropylmethylamines structurally related to (+)- and (-)-MPCB were synthesized and their binding affinities for sigma1, sigma2, opioid and dopamine (D2) receptors were evaluated. Substitution of the cis-N-normetazocine with different aminic moieties provided compounds with high affinity and selectivity for sigma binding sites with respect to opioid and dopamine (D2) receptors. The observed increase in sigma2 affinity as compared to the parent (+)-MPCB, supports the idea that the particular stereochemistry of (+)-cis-N-normetazocine affects sigma1 selectivity but does not affect sigma1 affinity. The (+/-)-cis isomers of methyl 2-[(1-adamantylamino)methyl]-1-phenylcyclopropane-1-carboxyl ate (18) displayed a higher affinity and selectivity for the sigma1 and sigma2 receptor subtypes compared to the (+/-)-trans 19. Interestingly, the enantiomer (-)-cis 18 displayed a preference for sigma1 receptor subtype whereas the (+)-cis 18 did for sigma2. These results prompt us to synthesize compounds with modification of nitrogen and carboxyl groups. The compounds obtained showed high affinities and selectivity for sigma sites. Moreover, modifications of carboxyl groups provided compounds with the highest affinities in the series. In particular, compound 25 with reverse-type ester showed a Ki of 0.6 and 4.05 nM for sigma1 and sigma2 binding sites, respectively.

Down-regulation of delta opioid receptor mRNA by an anabolic steroid in neuronal hybrid cells.

Nandrolone, an anabolic androgenic steroid, reduced delta opioid receptor (DOR) mRNA and the number of DOR binding sites in two neuronal hybrid cell lines: NG 108-15 and the GT1-1 cells. Both cell lines express DOR but only GT1-1 cells express androgen receptors (AR). DOR mRNA levels were maximally decreased by approximately 45% in NG 108-15 cells and by approximately 38% in GT1-1 cells exposed for 24 h to 10(-6) M nandrolone. This action was partly due to a decrease in the rate of transcription of DOR mRNA and was not blocked by the androgen antagonist flutamide. Flutamide antagonized the repression of AR mRNA induced by nandrolone. The synthetic glucocorticoid dexamethasone (10(-6) M) did not modify DOR steady-state transcripts in either cell line. These results suggest that nandrolone presumably regulate DOR mRNA levels through mechanisms independent of the androgen and glucocorticoid receptors.

Cyclic voiding cystourethrography in the diagnosis of occult vesicoureteric reflux.

Cyclic voiding cystourethrography (CVC) enhances the detection of vesicoureteric reflux (VUR). We investigated whether more-severe VUR may be overlooked, and whether older children are at risk of having their VUR missed with the conventional single-cycle study. Three hundred and seventy patients, 168 boys and 202 girls aged 1 month to 16 years, consecutively admitted over 1 year for suspicion of VUR, underwent two complete cycles of filling and voiding CVC. One hundred and four subjects, 33 boys and 71 girls, were older than 3 years (mean age 5.7 years, range 3.2-16 years). Sixty-six refluxing ureters from 51 patients were identified in the first cycle and 61 refluxing ureters from 45 patients were identified only with the second cycle. Four instances of grade IV VUR in 4 patients and three of grade V VUR in 3 patients were overlooked completely in the first cycle. Seven episodes of VUR < or = grade III from 5 patients diagnosed in the first cycle were upgraded to > or = grade IV at the second cycle. The presence of VUR was identified only in the second cycle in 35 of 74 subjects aged < or = 3 years and in 10 of 22 aged > 3 years (not significant). Of the 10 children aged > 3 years, 2, who had diagnosis only at the second cycle, had > or = grade IV VUR. More-severe VUR may be overlooked or down-graded in a single-cycle study. Two-cycle CVC is also useful in children older than 3 years.

Clinical presentation and natural course of idiopathic hypercalciuria in children.

Idiopathic hypercalciuria (IHC) has been reported mainly in children with hematuria in the 1980s and early 1990s, when renal sonography was just becoming routine. The presence of microcalculi, i.e., of hyperechogenic spots < 3 mm in diameter in renal calyces, was not taken into account in those studies. We attempted to outline clinical presentation and natural course of IHC not only in children with hematuria, but also in those with dysuria and/or recurrent abdominal/flank pain and a family history of nephrolithiasis, taking into account the finding of microcalculi. We analyzed retrospectively the data at diagnosis from 74 consecutive children aged 2.4-18 years (mean 8.6) with IHC (calciuria 4.1-15.1 mg kg-1 24 h-1, mean 6.1) and the outcome of 30 of them who were followed > or = 1 years (mean 3.2) with no specific therapy. At diagnosis, 38 patients (51%) had no hematuria, 42 (57%) had microcalculi and four (5%) had calculi. Of the patients with normal urinalysis, 71% had microcalculi or stones. The subjects with microcalculi and those with stones were significantly older than those without microcalculi and stones (P = 0.004 and 0.007). A normal urinalysis at our evaluation and a history of abdominal/flank pain were significantly more frequent in patients with microcalculi than in those without (P = 0.02 and 0.0001, respectively). During the follow-up, four of 30 patients formed stones 1-3 years after first diagnosis of IHC. More than half of children with IHC have microcalculi. The risk of formation of microcalculi or stones increases with age. The lack of hematuria does not exclude the presence of microcalculi or calculi. Hypercalciuria has to be suspected in children with dysuria and/or recurrent abdominal flank pain and a family history of nephrolithiasis, even when they have no hematuria.

Body growth in early diagnosed vesicoureteric reflux.

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.