First urinary tract infections in children: the role of the risk factors proposed by the Italian recommendations.

AIM: In 2009, the Italian society for paediatric nephrology suggested the need for cystography, following a first febrile urinary tract infection (UTI), only in children at high risk for dilating vesicoureteral reflux or in the event of a second infection. The aim of this study was to evaluate the adequacy of the risk factors proposed by the Italian guidelines. METHODS: Children aged 2-36 months, managed by 10 Italian hospitals between 2009 and 2013, with a first febrile UTI were retrospectively evaluated. RESULTS: Four hundred and fourteen children were included: 51% female, mean age eight months. Escherichia coli was responsible of 84% UTIs. 269 children (65%) presented at least one risk factor, thus were further investigated: 44% had a reflux. The presence of a pathogen other than E. coli significantly predicted high-grade reflux, both in the univariate (Odd Ratio 2.52, 95% Confidence Interval 1.32-4.81, p < 0.005) and multivariate analysis (OR 2.74, 95% CI: 1.39-5.41, p: 0.003). 26/145 children (18%) with no risk factors experienced a second UTI, which prompted the execution of cystography, showing a dilating reflux in 11. CONCLUSION: Among the risk factors proposed by the Italian guidelines, only the presence of a pathogen other than E. coli significantly predicted reflux. Cystography can be postponed in children with no risk factors.

HLA-B35, a common genetic trait, in a familial case of Henoch-Schoenlein purpura and Berger's disease.

Nephritis characterized by IgA mesangial depositions has been described both in Henoch-Schoenlein purpura (HSP) and in Berger's disease (BD), but common genetic traits are still uncertain. We report here the case of two brothers, the first affected by HSP with persistent nephritis and the second by BD, accidentally discovered as silent microhematuria 1 year after HSP onset in the first brother. HLA genotyping demonstrated the presence of HLA-B35 in both patients. Our findings reinforce the need to screen for urinary abnormalities in family members of patients affected by HSP nephritis to identify a silent IgA nephropathy.

Kidney length and scarring in children with urinary tract infection: importance of ultrasound scans.

BACKGROUND: Many studies have demonstrated that dimercaptosuccinic acid (DMSA) scintigraphy is the most sensitive diagnostic method in the identification of irreversible renal lesions (scars) in children with previous episodes of acute pyelonephritis (APN). This study assessed the reliability of ultrasound in identifying reflux nephropathy in children with acute pyelonephritis with or without vesicoureteric reflux (VUR). METHODS: Eighty children (45 female and 35 male, age range 5 months to 10 years, average age 2 years 1 month) with a positive history for at least one episode of APN participated in this study. All children underwent voiding cystourethrography, DMSA scintigraphy 4 to 8 months after the most recent episode of APN, and an ultrasound test evaluation less than 2 months after DMSA scintigraphy. RESULTS: Voiding cystourethrograms showed VUR in 52 children (68%); 13 of these were bilateral, for a total of 65 refluxing kidney units of the 154 (42%) evaluated; DMSA scintigram was normal for 108 of 154 kidneys (70%). Of the 65 kidneys with VUR, DMSA scintigram displayed normal findings in 29 cases (45%) and pathologic findings in 36 (55%). In the 79 nonrefluxing kidneys, DMSA scintigram was normal in 69 cases (87%). The relative risk of scarring in VUR kidneys is 2.6. The ultrasound study recorded a maximum longitudinal diameter between the 5th and 95th percentiles in 80 of 89 (81%) kidneys without VUR and in 21 of 65 (32%) with VUR. A significant correlation was found between maximum longitudinal diameters and DMSA scintigraphic findings in kidneys with VUR and those without VUR, respectively. CONCLUSION: This study establishes that ultrasound scans, by means of a simple and reproducible measurement technique, maximum longitudinal diameter, have a predictive value with regard to the presence of scars, with few exceptions. This finding, in our opinion, could lead to a decrease in the number of invasive procedures, in particular DMSA scan, in patients with APN.

UV- and midwave-sensitive cone-driven retinal responses of the mouse: a possible phenotype for coexpression of cone photopigments.

Molecular biological, histological and flicker electroretinographic results have established that mice have two cone photopigments, one peaking near 350 nm (UV-cone pigment) and a second near 510 nm [midwave (M)-cone pigment]. The goal of this investigation was to measure the action spectra and absolute sensitivities of the UV-cone- and M-cone-driven b-wave responses of C57BL/6 mice. To achieve this goal, we suppressed rod-driven signals with steady or flashed backgrounds and obtained intensity-response relations for cone-driven b-waves elicited by narrowband flashes between 340 and 600 nm. The derived cone action spectra can be described as retinal1 pigments with peaks at 355 and 508 nm. The UV peak had an absolute sensitivity of approximately 8 nV/(photon microm2) at the cornea, approximately fourfold higher than the M peak. In an attempt to isolate UV-cone-driven responses, it was discovered that an orange conditioning flash (lambda > 530 nm) completely suppressed ERG signals driven by both M pigment- and UV pigment-containing cones. Analysis showed that the orange flash could not have produced a detectable response in the UV-cone pathway were their no linkage between M pigment- and UV pigment-generated signals. Because cones containing predominantly the UV and M pigments have been shown to be located largely in separate parts of the mouse retina (), the most probable linkage is coexpression of M pigment in cones primarily expressing UV pigment. New histological evidence supports this interpretation (). Our data are consistent with an upper bound of approximately 3% coexpression of M pigment in the cones that express mostly the UV pigment.

Extreme responsiveness of the pupil of the dark-adapted mouse to steady retinal illumination.

PURPOSE: To measure the dependence of the size of the pupils of mice on steady retinal illumination. METHODS: Anesthetized C57BL/6 mice aged 7 to 8 weeks were placed in a ganzfeld chamber in darkness, and in monochromatic (510 nm) and white light whose intensity was varied more than 6 log units. The pupils of the mice were photographed with an infrared video camera and recorded on videotape and the pupil areas determined by digital image analysis of the video recordings. RESULTS: Fully dark-adapted murine pupils had an area of 2.29 +/- 0.35 mm2. The minimum pupil size at saturating intensity was 0.10 +/- 0.05 mm2. The steady state pupil area declined to half its dark-adapted maximum when ganzfeld luminance was 10(-5) scotopic candela (scot. cd) per meter squared. Pupil area declined to 20% of the dark-adapted magnitude at approximately 10(-3) scot. cd/m2. CONCLUSIONS: The mouse pupil can regulate retinal illumination by a factor exceeding 20. The neural circuitry that determines steady state murine pupil size is extremely sensitive to retinal illumination and under these experimental conditions is controlled almost exclusively by rod signals. This follows, because the ganzfeld illuminance (10(-5) scot. cd/m2) that causes the pupil to constrict to half its dark-adapted value corresponds to only approximately 0.01 photoisomerization per rod per second, whereas 80% reduction in pupil area occurs at approximately 1 photoisomerization per rod per sec. Based on this extreme responsiveness to steady illumination, the hypothesis is proposed that the murine pupil functions to protect a retinal circuit that can become saturated at extremely low photon capture rates. General principles of dark-adapted retinal circuitry support the identification of the first three neurons in the circuit as the rod, the rod bipolar, and the AII-amacrine. The rod and rod bipolar neurons do not approach saturation at the intensities at which the pupil constricts, however, and it seems unlikely that the AII-amacrine does. Thus the retinal neurons protected from saturation by the mouse pupil constrictions are probably ganglion cells with large receptive fields that have sustained responses.

Prevalence of celiac disease in patients with juvenile chronic arthritis.

We estimated the prevalence of celiac disease in children with juvenile chronic arthritis (JCA), using antiendomysium antibodies as the screening test to select patients for intestinal biopsy. We studied 119 children with JCA and found four patients with antiendomysium antibodies. In three of these patients (2.5%), intestinal biopsy revealed villous atrophy; in the fourth the intestinal mucosa was normal. We conclude that the prevalence of celiac disease is increased in patients with JCA.

[Vascular hyperfragility in systemic lupus erythematosus treated with low doses of cortisone]. / Iperfragilità vascolare in corso di lupus eritematoso sistemico trattato con basse dosi di cortisone.

We report an unusual cutaneous manifestation of systemic lupus erythematosus (SLE) in a 15-year old female. The diagnosis was made on the basis of clinical symptoms, cutaneous hystology (positive "lupus band test") and on laboratory findings (hypocomplementemia, positive antinuclear antibodies and rheumatoid factor). Treatment with methylprednisolone (0.5 mg/kg/die) improved the clinical symptoms but, after 2 months, large ecchymotic lesions appeared on the lower legs below the knee extending as far as the ankles, likely triggered by minor local traumas. Coagulative function was normal, the lupic anti-coagulant factor (LAF) was negative, anticardiolipin antibodies were absent and there was no thrombocytopenia. There was only a slight increase in clotting times in vitro, in presence of ADP. The amount of cortisone was reduced and the type of treatment modified; satisfactory control of the disease was attained with deflazacort (0.3 mg/kg/die). The ecchymosis on the lower limbs never disappeared even though they became slightly smaller. Ecchymotic lesions are not usually included in the wide range of cutaneous manifestations associated with SLE. Moreover vascular fragility resulting from pressure and minor traumas is known to be a cutaneous complication of hypercorticism; nevertheless the doses of cortisone administered to this patient were rather low and other clinical signs of steroid hyper-dosing were absent although cortisolemia assay at base and after stimulus with ACTH was not performed. We would suggest that the negligible platelet binding defect (whether primary or SLE-associated) together with the low amounts of cortisone administered caused ecchymotic lesions to appear in this patient suffering from a disease (SLE), in which the small cutaneous vessels are favourite targets.

[Systemic lupus erythematosus: description of a pediatric series]. / Lupus eritematoso sistemico: descrizione di una casistica pediatrica.

We describe 11 cases of Systemic Lupus Erythematosus (SLE) with pediatric onset (10 females and 1 male). Mean age at onset was 10.9 years (range 3 to 16 years). Initial manifestations: cutaneous involvement in 7 cases, articular symptoms in 7 cases, renal involvement in 5 cases (proteinuria and/or microhematuria, or renal failure), pancytopenia in 3 cases. In 3 cases the onset of the disease was extremely sudden and severe: one patient had an intestinal infarct following mesenteric thrombosis associated with glomerulonephritis; another started with encephalopathy (deep coma, stage III); a third patient presented renal failure due to acute glomerulonephritis. At diagnosis all patients received systemic steroid therapy with the exception of one who had only a cutaneous involvement. The course of the disease is described. We underline that, in our series, it was rare for organs and systems, apart from the central nervous system, to be involved in exacerbations after initial onset of the disease. Six patients are presently asymptomatic or have only minor cutaneous and/or articular manifestations which are well controlled with low-dose cortisone therapy. Laboratory indices did not return to normal in any of the patients. In fact, in our series the disease doesn't appear to reach a complete remission, even many years after onset and no patient seems to be able to withdrawal the therapy at all. Our data confirm, according to other Authors, that the course of LES with paediatric onset is more severe than in adults.

Study of IL-2, IL-6, TNF alpha, IFN gamma and beta in the serum and synovial fluid of patients with juvenile chronic arthritis.

In the last few years the important role played by various cytokines in the pathogenesis of chronic inflammatory diseases has emerged. In the present study, serum and synovial fluid levels of IL-2, IL-6, TNF alpha, IFN beta and IFN gamma were evaluated in a group of 66 patients with juvenile chronic arthritis (JCA). At the same time the ESR, CRP, hemoglobin, immunoglobulins, platelet count and Ritchie index were measured. In the serum of pauciarticular patients, IL-6 and TNF alpha levels were only slightly elevated compared with controls, but there was no correlation between these cytokines and clinical and other laboratory parameters. Serum IL-2 and IFN gamma were undetectable. In contrast, in the synovial fluid IL-6 levels were very high in all of the patients examined and there was a significant correlation between synovial fluid IL-6 levels and Ritchie's articular index. TNF alpha tended to be elevated but to a lesser extent, while synovial fluid IL-2 and IFN gamma were undetectable or very low, as in the serum. In polyarticular and systemic patients, on the other hand, serum IL-6 was elevated and statistically correlated with the majority of the laboratory parameters and with the Ritchie articular index. TNF alpha levels were only slightly elevated; on the other hand, IL-2 and IFN gamma were undetectable. There was an inverse correlation between IFN beta levels and the Ritchie articular index and a significant correlation with hemoglobin levels. In conclusion, our study demonstrates that not only IL-1 (as shown in other studies), but also IL-6 and to a lesser extent TNF alpha play a central role in the pathogenesis of JCA. IFN beta on the other hand, would seem to play an anti-inflammatory role.

Localized scleroderma after infection with Epstein-Barr virus.

Over a period of three years (1989-1992) five children suffering from localized scleroderma were seen at the Department of Pediatrics of the University of Trieste. Evidence of a previous infectious mononucleosis (IM) was present in four out of five patients. The clinical history of these four children is reported. The association between the appearance of scleroderma and a previous viral infection is not surprising. However, in the pediatric literature there is only one case of progressive systemic sclerosis (PSS) developing in a 15-month-old girl less than one month after she contracted IM. The presence of shared epitopes between an Epstein-Barr virus protein, BOLF1, and the hypervariable region of HLA associated with the pauciarticular form of JCA, recently reported, could provide a key to the pathogenesis of other collagen diseases such as scleroderma.

Anti-alpha-gliadin antibodies are not predictive of celiac disease in juvenile chronic arthritis.

Some authors have recently reported an increased level of antigluten antibodies in rheumatoid arthritis, both in the adult and juvenile form. The real meaning of these antibodies is still unclear. We ascertained the levels of antigluten antibodies in a group of children with juvenile chronic arthritis to determine if these antibodies were linked with celiac disease and/or to increased intestinal permeability. In 18 of 53 patients (33.9%), the levels of antigluten antibodies (IgA or IgG) were higher than normal. No correlation was found between the increase in antigluten antibodies and the positive lactulose/mannitol test, used for determining increased intestinal permeability. In all eight patients undergoing intestinal biopsy due to abnormal levels of antigluten antibodies (IgA class), intestinal mucosa was normal. In conclusion, our study shows that in patients with juvenile chronic arthritis, immunological response to gluten is neither related to celiac disease nor to increased intestinal permeability.

[Treatment with low-dose methotrexate in intractable juvenile chronic arthritis]. / Trattamento con metotrexate a basse dosi nell'artrite cronica giovanile intrattabile.

14 patients suffering from Juvenile Chronic Arthritis unresponsive to NSAIDS were enrolled in this open study. There were two patients with a systemic form, nine patients with polyarticular form. All patients received methotrexate administered orally in one or two divided doses; the dose was 0.3-0.5 mg/kg/week. Clinical improvement occurred in most of the cases; remission was achieved in 5 out of 9 polyarticular form, in one out of the two systemic form and in two out of the three pauciarticular form. All patients showed a significant improvement in the clinical parameters except one with a pauciarticular form (duration of morning stiffness, number of swollen joints and number of painful joints). The effects on laboratory indexes were a decrease in ESR and CRP in about 50% of the cases, an increase up to the normal value of hemoglobin in about 30% of the cases. Two patients experienced a transient gastrointestinal discomfort and 3 had a mild elevation of serum aminotransferase levels which were restored after a reduction of the drug. In conclusion our data confirm that methotrexate at low dosage is more effective than other second-line agents and has fewer side effects. In our opinion methotrexate can today be considered the first choice for Juvenile Chronic Arthritis unresponsive to NSAIDS.

Treatment and prevention of osteoporosis in juvenile chronic arthritis with disodium clodronate.

Osteoporosis is one of the most difficult problems in the management of Chronic Juvenile Arthritis (JCA). The available data suggest that bone loss results from multifactorial processes which lead to bone degradation through the activation of osteoclasts. Biphosphonates are synthetic factors that, once localized on the surface of hydroxyapatite crystals, do not allow either the production or destruction of the crystals. This activity seems to be due to cytotoxicity against osteoclasts and to inhibition of prostaglandin E2 synthesis. There is some evidence that these drugs are effective in the treatment of osteoporosis in several diseases. In an attempt to reduce or prevent osteoporosis in children affected by JCA we started a trial with disodium clodronate, a type of biphosphonate. Thirteen patients were enrolled in the study: 7 received disodium clodronate and 6 acted as control subjects. Before starting the therapy and after one year we performed a CT scan to evaluate the mineral bone density in all patients. The mean bone density increased from a bone mineral content of 129 mg/cc before treatment to 134 mg/cc after treatment (8% increase); control patients passed from 123 mg/cc to 115 mg/cc (7% decrease) in the same period. Only one child stopped treatment because of gastrointestinal side effects. The small number of patients enrolled in the trial does not allow any definite conclusions to be drawn, but the data are interesting and worthy of further study.

[Long-term remission induced by measles infection and followed by immunosuppressive therapy in a case of refractory juvenile rheumatoid arthritis]. / Remissione a lungo termine in caso di artrite reumatoide giovanile intrattabile indotta da infezione morbillosa seguita da terapia immunosoppressiva.

A case of severe juvenile rheumatoid arthritis, polyarticular type, refractory to FANS and long acting therapy which showed a quick remission after measles is described. An immunosuppressive therapy to strengthen the immunosuppression induced by virus infection was performed for six months. The remission has been maintained for 4 years and appears up to now to be stable with no therapy. On the basis of this observation, the possibility of a vaccination therapy with measles virus, which equally gives immunosuppression, is discussed.