The Greek version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient-reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Greek language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographics, clinical data, and the JAMAR from 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability, and construct validity (convergent and discriminant validity). The Greek JAMAR was fully cross-culturally adapted with two forward and three backward translations. A total of 272 JIA patients (5.9% systemic, 57.7% oligoarticular, 21.3% RF negative poly-arthritis, 15.1% other categories), and 100 healthy children were enrolled in all centres. The JAMAR components discriminated well-healthy subjects from JIA patients; notably, there was no significant difference between healthy subjects and their affected peers in psychosocial quality of life and school-related items. All JAMAR components revealed good psychometric performances. In conclusion, the Greek version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and in clinical research.

ROBO2 gene variants in children with primary nonsyndromic vesicoureteral reflux with or without renal hypoplasia/dysplasia.

BACKGROUND: Primary nonsyndromic vesicoureteral reflux (VUR) and VUR with renal hypoplasia/dysplasia (VUR-RHD) are common congenital anomalies of the kidney and urinary tract (CAKUT). Sequence variations of the ROBO2 gene were investigated in children with nonsyndromic VUR or VUR-RHD. METHODS: Single-strand conformation polymorphism (SSCP) electrophoresis or multiple restriction fragment SSCP (MRF-SSCP), followed occasionally by direct sequencing, was used to screen 103 patients and 200 controls for nucleotide changes. Gene polymorphisms and transposable elements were investigated using bioinformatics. RESULTS: Two single-nucleotide polymorphisms were detected: IVS1-53 and IVS5-31. The frequency of A allele of IVS1-53G>A did not differ significantly between patients and controls. IVS1-53 does not affect mRNA splicing according to in silico analysis. IVS5-31A>G substitution was found in one patient, reported here for the first time in VUR. In silico results demonstrated alteration in two serine/arginine-rich (SR) protein-binding sites and two additional acceptor sites. The ROBO2 gene sequence was found to contain 25.9% transposable elements. CONCLUSION: ROBO2 variants were not found to be associated with nonsyndromic VUR or VUR-RHD, providing further evidence for genetic heterogeneity. The role of transposable elements in ROBO2 gene expression in CAKUT needs further investigation since they are generally considered to be mutagens.

Arterial hypertension during treatment with triptorelin in a child with Williams-Beuren syndrome.

BACKGROUND: Arterial hypertension (AHT) is a common finding in children with Williams-Beuren syndrome (WBS). Although cardiovascular and renal abnormalities can explain the AHT in some patients with WBS, its etiology is not fully understood and most cases are considered idiopathic. CASE-DIAGNOSIS/TREATMENT: The case is reported of a 10-year-old girl with WBS who developed severe AHT during treatment with triptorelin, a long-lasting gonadotropin-releasing hormone (GnRH) analog, administered because of early normal puberty. Comprehensive diagnostic studies ruled out other known causes of AHT associated with WBS. After discontinuation of triptorelin, the blood pressure remained within the normal range for her age and height with no antihypertensive treatment on long-term follow-up. To the best of the authors' knowledge, this is the first report of AHT associated with triptorelin administration in a child with WBS. CONCLUSIONS: Clinicians should be aware of the possibility, although rare, of AHT developing during triptorelin administration in childhood, specifically in patients at increased risk of AHT, such as those with WBS.

Growth and function in childhood of a normal solitary kidney from birth or from early infancy.

BACKGROUND: Children with a solitary kidney (SK) have an increased long-term risk of hypertension, albuminuria and glomerulosclerosis. In this study, we assessed the early signs of impaired glomerular filtration in children with a SK from birth or from early infancy. METHODS: Renal growth and function at ages 4-15.5 years were studied in 38 children with SK and 40 matched control subjects in terms of accelerated growth. RESULTS: The systolic/diastolic blood pressure Z-scores (p = 0.01/<0.05) and the resistance index (RI) of the arcuate arteries (p = 0.05) were higher in the children with SK. Creatinine clearance and 24-h protein and albumin urinary excretion showed no difference. All but seven children with SK had 99mTc diethylene-triamine pentaacetic acid glomerular filtration rate values of >80 ml/min/1.73 m(2). An independent positive correlation was found between length of the follow-up time and 24-h albumin urinary excretion (ß = 0.54, p < 0.01). Accelerated postnatal growth was positively related with kidney volume (ß = 0.35, p < 0.05). CONCLUSIONS: Among our patient cohort, renal function was well preserved at ages 4-15.5 years in children who were born with a SK. However, both their higher blood pressure and RI and the correlation of 24-h albumin urinary excretion with length of follow-up time underline the need for monitoring to detect early signs of glomerular hyperfiltration and, if necessary, implement timely intervention. SK hypertrophy was found to be correlated with postnatal growth.

Changes in vascular function and structure in juvenile idiopathic arthritis.

OBJECTIVE: Chronic inflammatory diseases in adults have been associated with increased cardiovascular risk and impaired vascular function. We aimed to assess the presence of early vascular dysfunction in patients with juvenile idiopathic arthritis (JIA) and investigate the role of inherent inflammatory process of JIA in vascular health. METHODS: Thirty patients with JIA (age range 7-18 years) were compared to 33 age- and sex-matched controls. Endothelial function (brachial artery flow-mediated dilation [FMD]), carotid intima-media thickness (IMT), and arterial stiffness were examined. Endothelial inflammation was assessed by intercellular adhesion molecule 1 (ICAM-1) and P-selectin measurements. RESULTS: Patients with JIA showed decreased FMD compared to controls (P = 0.001), independent of age (P = 0.9 among age subgroups). Baseline differences in erythrocyte sedimentation rate, ICAM-1, and glucose between the 2 groups accounted for the difference in FMD. The presence of systemic JIA was associated with greater IMT compared to patients with oligoarticular disease, polyarticular disease, or controls (P = 0.014, P = 0.069, and P = 0.046, respectively). The difference in IMT between systemic versus oligoarticular/polyarticular JIA was attributed to the following risk factors: age, body mass index, blood pressure, disease activity, and corticosteroids use. There were no differences in arterial stiffness indices between JIA patients and controls or between patients with systemic versus nonsystemic disease. CONCLUSION: Endothelial function is impaired in patients with JIA at a very young age, while IMT is increased only in the presence of systemic JIA. Vascular dysfunction may be partly attributed to the effects of disease-related characteristics (inflammation, disease activity, and medications).

Implications of 99mTc-DMSA scintigraphy performed during urinary tract infection in neonates.

OBJECTIVE: To evaluate prospectively whether normal scintigraphic results during urinary tract infections (UTIs) in neonates were predictive of the absence of dilating vesicoureteral reflux (VUR) (grade > or =III) and permanent renal damage (PRD). METHODS: Term neonates with a first symptomatic, community-acquired UTI participated in the study. Urinary tract ultrasonography and technetium-99m-labeled dimercaptosuccinic acid ((99m)Tc-DMSA) scintigraphy were performed within 72 hours after diagnosis and voiding cystourethrography within 1 to 2 months. DMSA scintigraphy, to determine the development of PRD, was repeated 6 months after UTI. RESULTS: Seventy-two neonates (144 renal units) were enrolled. Acute pyelonephritis was diagnosed through early DMSA scintigraphy in 19% of renal units, VUR in 22%, and grade > or =III VUR in 13%. The majority (71%) of renal units with grade > or =III VUR had normal early DMSA scintigraphic results. The sensitivity and specificity of abnormal early DMSA scintigraphic results to predict grade > or =III VUR were 29% (95% confidence interval: 11%-55%) and 82% (95% confidence interval: 74%-88%), respectively. PRD was found in 7% of renal units, all of which had abnormal early DMSA scintigraphic results. PRD was significantly more frequent among renal units with grade > or =III VUR than among nonrefluxing renal units (P < .05). CONCLUSIONS: Normal early DMSA scintigraphic results for neonates with symptomatic UTIs were helpful in ruling out later development of PRD but were not predictive of the absence of dilating VUR. To rule out dilating VUR, voiding cystourethrography may be required.

Absence of mutations in the HOXA11 and HOXD11 genes in children with congenital renal malformations.

Experimental studies have shown that homeobox genes are essential for the development of the kidney and urinary tract. Hoxa11/Hoxd11 double mutant mice demonstrate renal agenesis or hypoplasia. Since, to our knowledge, these genes have never been examined for alterations in humans with congenital anomalies of the kidney and urinary tract (CAKUT), we investigated whether mutations of HOXA11/HOXD11 genes are associated with non-syndromal congenital renal parenchymal malformations. DNA samples from 26 unrelated children with unilateral renal agenesis (URA), 20 with renal hypodysplasia (RHD) and 13 with multicystic dysplastic kidney (MCDK) were included in the study. Exons 1 and 2 of the HOXA11/HOXD11 genes were amplified individually by polymerase chain reaction (PCR) using 12 unique oligonucleotide primers. Single-strand conformation polymorphism (SSCP) analysis of overlapping polymerase chain reaction products was performed. SSCP analysis revealed no variant band shifts in the samples of the amplified segments of the 59 patients, suggesting lack of either mutation or polymorphisms. Our findings do not support the hypothesis that mutations in the HOXA11/HOXD11 coding regions are involved in the pathogenesis of human non-syndromal congenital renal parenchymal malformations. Further studies are necessary, since other genes known to affect nephrogenesis, as well as genetic and environmental factors, may be involved.

Orbital cavernous hemangioma in an infant with intracranial lesions: a case report.

INTRODUCTION: Cavernous hemangiomas of the orbit are benign vascular malformations, commonly encountered in adults. Although they are infrequent in pediatric population their diagnosis and course are of a great significance, mainly because they can cause visual disturbances such as amblyopia that can ensue, and secondarily due to their cosmetic and psychological effect. Special attention is required in follow up and treatment. Additionally, a systemic evaluation is necessary in order to discover asymptomatic lesions elsewhere in the body carrying a risk of complications. CASE PRESENTATION: The authors describe the clinical course, diagnosis, therapeutic approach and prognosis of an infant with an orbital cavernous hemangioma accompanying intracranial lesions. A female infant 18 months of age, presented with a mass in the left upper eyelid, causing blepharoptosis. Preoperative magnetic resonance imaging and angiography of the brain and the orbits showed a hemangioma of the left upper eyelid and intracranial lesions to the left temporal fossa and the pons. At the age of 2 years and 8 months she was admitted again due to severe eyelid swelling, intense strong pain, exophthalmos and collateral ophthalmoplegia. Two operations were performed to remove the orbit mass. Histological examination, showed characteristics of cavernous hemangioma. CONCLUSION: The atypical presentation of cavernous orbital hemangioma with early infantile onset, merits attention.

Temporomandibular joint involvement in juvenile idiopathic arthritis: clinical predictors of magnetic resonance imaging signs.

The aim of the study was to define clinical predictors of magnetic resonance imaging (MRI) findings of temporomandibular joint (TMJ) involvement in juvenile idiopathic arthritis (JIA). Forty-six patients, aged 2.08-36.7 years, with JIA (oligoartitular 18, polyarticular 17, systemic type 11) were examined with standard plain and contrast-enhanced sequences. Of 88 TMJs examined, an abnormal condyle was observed in 32%, flattened articular eminence in 27%, flattened articular disk in 17%, intra-articular fluid in 10%, enhancing pannus in 45% and restricted condylar motion in 9%. Logistic regression analysis revealed that for abnormal condyle and flattened articular eminence, independent predictors were type of JIA (P < 0.015), age at onset (P < 0.038), and duration of disease activity (P < 0.001). Plots of the logistic regression models showed that TMJ involvement approached certainty for systemic sooner than for the other JIA types. Pannus was present with probability >0.5 when the disease started before 4 years of age. In conclusion, the systemic type of JIA, young age at onset and long duration of activity are risk factors for TMJ damage. MRI of the TMJ should be performed in patients who are less than 4 years of age at the onset of JIA, and in those with the systemic type, whatever the age of onset.

Masked severe stenosing ureteritis: a rare complication of Henoch-Schönlein purpura.

Henoch-Schönlein purpura (HSP)-associated stenosing ureteritis represents a rare complication of the disease, typically presenting with severe manifestations. This article reports on a 3.5-year-old boy with HSP and severe nephritis who developed a unilateral stenosing ureteritis with atypical manifestations, resulting in a nonfunctional kidney and consequent nephrectomy. The urinary tract ultrasound was normal in the first week of illness, and the diagnosis was made during follow-up 8 months after onset. The predominance of nephritic manifestations may have masked any signs of ureteritis, leading to the delay in diagnosis. To clarify the clinical spectrum of this complication, an extensive review of the literature was performed. We emphasize the necessity of repeated urinary tract ultrasound both early and later in the course of HSP, especially in cases with renal involvement, so that an early diagnosis of this complication can prevent a potentially serious renal outcome.

Rare combination of unilateral renal agenesis, congenital obstructive posterior urethral membrane, and enlarged prostatic utricle, with absence of hydroureteronephrosis.

The existence of congenital obstructive posterior urethral membrane (COPUM), extending proximally from the verumontanum toward the bladder neck, has been widely debated. Although COPUM often leads to chronic renal disease, a milder degree of obstruction and protective pressure pop-off mechanisms have been reported. We present a male infant with a rare combination of unilateral renal agenesis, COPUM proximally from the verumontanum to the bladder neck, and enlarged prostatic utricle. The posterior urethra was dilated, without bladder abnormalities or hydroureteronephrosis, indicating milder obstruction. Moreover, the enlarged prostatic utricle could contribute in the urinary tract protection, serving as an uncommon pressure pop-off mechanism.

Angiotensin II type 2 receptor gene polymorphism in Caucasian children with a wide spectrum of congenital anomalies of the kidney and urinary tract.

The A-1332G transition of the angiotensin II type 2 receptor (AT2R) gene was found to occur more often in males with ureteropelvic (UPJO) or ureterovesical junction obstruction (UVJO). However, other studies have shown controversial results. Tauhe frequency of this polymorphism was investigated in 275 Caucasian children (153 boys, 122 girls) with a wide spectrum of congenital anomalies both of upper (165) and lower (110) urinary tract system and in 200 controls (100 boys, 100 girls). Among the included malformations, renal agenesis and duplex collecting system (DCS) were studied for the first time. The frequency of the G allele did not differ among patients (193 of 397 total alleles, 48.6%) and controls (146 of 300, 48.7%). No significant difference was also found in the frequency of the G allele in subgroups of congenital uropathies compared with controls. When analysis was performed in males and females separately, no significant difference was found in the frequency of the G allele in male (45.1%) or female (50.8%) patients compared with male (57.0%) or female (44.5%) controls. Our data indicate that the AT2R gene A-1332G transition is not associated with the development of human congenital uropathies and further investigations should be carried out to unravel their etiology.

Provocation of neurocardiogenic syncope during head-up tilt testing in children: comparison between isoproterenol and nitroglycerin.

OBJECTIVE: Although nitroglycerin- and isoproterenol-augmented tilt tests are of equal value in the diagnosis of neurocardiogenic syncope in adults, no data exist in children. We compared the sensitivity and specificity of the 2 tests in a pediatric population. PATIENTS AND METHODS: We studied 85 patients (33 boys; mean age: 11.6 +/- 2.9 years). Of them, 56 had a diagnostic history of neurocardiogenic syncope, whereas 29 served as controls. After a negative passive phase, they were randomly assigned to either intravenous isoproterenol or sublingual nitroglycerin, and tilt was continued for 20 minutes. RESULTS: Sensitivity was 0.78 for the isoproterenol test and 0.79 for the nitroglycerin test, but specificity was significantly higher for isoproterenol test compared with nitroglycerin test. In patients with a positive test, the duration of the recovery period was significantly longer after nitroglycerin (8.4 +/- 2.7 minutes) than after isoproterenol (5.1 +/- 1.6 minutes). CONCLUSIONS: Nitroglycerin- and isoproterenol-augmented tilt tests are associated with equal sensitivity in the diagnosis of neurocardiogenic syncope in children and adolescents. However, nitroglycerin results in more false-positive tests and produces more prolonged vasovagal symptoms. Our data do not support the routine use of nitroglycerin in the evaluation of syncope in this age group.

Cyclic contrast-enhanced harmonic voiding urosonography for the evaluation of reflux. Can we keep the cost of the examination low?

The purpose of this study was to evaluate whether a second cycle of contrast-enhanced voiding urosonography (VUS) with no added contrast medium (CM) can increase the detection rate of vesicoureteral reflux (VUR). One hundred twelve consecutive children with a mean age of 2.9 years with 224 kidney-ureter units (KUU) underwent two cycles of contrast-enhanced harmonic VUS. The first cycle of VUS was performed with 3.5-12.5 ml of suspension 300 mg/ml SH U 508 A and was followed immediately by a second cycle with only saline without adding CM. VUR was detected in 57 KUU from 44 children (39%) at the first cycle of VUS. Eight of the remaining 68 non-refluxing children (12%) demonstrated VUR at the second cycle (P=0.045). Most cases of missed reflux at the first cycle were grade II (75%). However, in two KUU from two children missed reflux was grade III. In one child reflux (grade II) was missed on the second cycle. Comparing the second cycle of VUS with the first cycle, concordant findings regarding the presence or absence as well as the grade of reflux were found in 94% of KUU. A second cycle of contrast-enhanced harmonic VUS with no added CM discloses significantly more cases of VUR at no additional cost for the examination.

Duplex collecting system diagnosed during the first 6 years of life after a first urinary tract infection: a study of 63 children.

PURPOSE: We determined the prevalence, anatomical variants and coexisting complications of duplex collecting systems in children with a history of UTI. Additionally, we compared the prevalence and severity of the coexisting anomalies with those found in single systems. MATERIALS AND METHODS: We reviewed the records of children younger than 6 years who were evaluated following a first UTI during a 9-year period to identify those with duplex systems. Children without duplication anomalies comprised the control group. RESULTS: Of 774 evaluated children 63 (8%), more commonly females than males, had duplex systems. CDS were as common as IDS. VUR was the most commonly associated anomaly, with a higher prevalence in CDS (66%) and IDS (47%) compared to single systems (26%, p <0.0001 and p = 0.007, respectively). Ectopic ureterocele, which was the second most common associated anomaly, was found in 20% of the CDS but in none of the IDS or single systems. The occurrence of renal scarring was similar among CDS, IDS (13%) and single systems (10%). Poorly functioning pole moieties occurred more often in CDS (40%) compared to IDS (4%, p = 0.003), and were observed in none of the single systems. The resolution rate of reflux tended to be higher in IDS compared to CDS. CONCLUSIONS: CDS were a common finding among children with UTI who had duplication anomalies. Although CDS and IDS were accompanied by VUR more often than were single systems, CDS were associated more often with severe VUR, other serious complications and poor renal function.

Total hip arthroplasty in children with juvenile chronic arthritis: long-term results.

From 1984 to 2002, 20 total hip arthroplasties in children with juvenile chronic arthritis were performed in the authors' department. All patients had polyarticular disease. Average age of patients was 15.8 (range 13-24) years. Early onset of the disease occurred at an average age of 7.3 (4-10) years. In six patients the physes were open at the time of surgery. All patients had complete loss of joint space and various combinations of subchondral sclerosis, flattening of the femoral head, and anterior inclination of the neck. All patients used crutches for walking and joint function was very restricted. All patients were operated on under general anesthesia. One of them was supported additionally with laryngeal mask because of cervical spine involvement. No intra- or postoperative complications occurred. Mobilization of the patients started immediately after surgery, followed by a special rehabilitation program. Follow-up examination was based on the Merle d'Aubigne et Postel scale as modified by Charnley. Patients were followed at 6 weeks and 3 months after surgery and thereafter every 6 months with clinical and radiologic examination. Average follow-up was 9.2 (2-20) years. All patients had no pain and full functional ability. Although total hip arthroplasty is technically difficult in this age, it should be performed in specialized centers because pain relief, decreased deformity, and improved quality of life can be achieved in most patients. The only disadvantage is wear of the prosthesis.

Total hip and knee arthroplasty for juvenile rheumatoid arthritis.

We performed 23 total hip and knee arthroplasties (15 total hip and 8 total knee arthroplasties) in 18 children with juvenile rheumatoid arthritis between 1984 and 2001. The mean age at surgery was 17.8 years (range 13 to 24 years). The age of presentation of the disease was from 4 to 10 years with average 7.3 years. The average length of follow-up was 9.7 years (range 7 to 16 years). All patients conformed with the American Rheumatism Association criteria for juvenile rheumatoid arthritis. All patients had complete loss of joint space and various combination of subchondral sclerosis, flattening of the femoral head, anterior inclination of the neck. Three knees were diagnosed with bony ankylosis. Follow-up was based on the Merle d'Aubigne et Postel scale modified by Charnley. One acetabular component has been revised to date. No femoral or tibial components have been revised. No patient had pain post-operatively and function was very satisfactory. Total hip and knee arthroplasties are technically difficult to execute in this age and should be performed in specialized centers. With appropriate indications pain relief,decrease of deformity and improvement of quality of life can be achieved in most patients.

Genetic risk factors associated with thrombosis in children with congenital neurologic disorders.

Thromboembolic events during the perinatal period are responsible for irreversible brain damage owing to cerebral hypoxia and neuronal necrosis. We investigated the presence of thrombophilia risk factors in children with congenital neurologic disorders. Nineteen children (9 males and 10 females), aged 1 to 14 years (median 4.5 years), who had presented with symptoms and signs of congenital neurologic disorders were studied. Thirty-five age-matched healthy children recruited from the same geographic area served as controls. Three patients of 19 (15.8%) were carrying the factor V Leiden mutation compared with 2 children among the controls (5.7%). One patient was heterozygous for the prothrombin G20210A variant (5.2%) compared with one child who was heterozygous among the controls. Three patients were homozygous (15.8%) and 11 were heterozygous (57.9%) for the C677T 5,10-methylenetetrahydrofolate reductase gene mutation compared with 4 (11.5%) and 18 (51.4%), respectively, among the controls. Three patients of 19 (15.8%) were carrying more than one mutation. We found 18 mutations in 79% (15/19) of the patients and 25 mutations in 69% (24/35) of the healthy children. Among the individuals carrying the homozygous 677TT 5,10-methylenetetrahydrofolate reductase genotype, we found 7 mutations in 32% (6/19) of the patients and 7 mutations in 20% (7/35) of the healthy children (P > .05). In one patient, lupus anticoagulant and antiphospholipid antibodies of IgG isotype were detected. Reduced activities of protein C, protein S, or antithrombin III were not observed in either the patient or the control group. Although, among our cases, we found some well-known risk factors associated with thrombosis in adults, the pathogenesis of these clinical entities remains obscure.