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The issue of quality assurance (QA) and quality improvement (QI), being the quality of medical education intimately related to the quality of the health care, is becoming of paramount importance worldwide.To describe a model of implementing a system for internal QA and QI within a post-graduate paediatric training programme based on the ISO 9001:2000 standard.For the ISO 9001:2000 standard, the curriculum was managed as a series of interrelated processes and their level of function was monitored by ad hoc elaborated objective indicators.The training programme was fragmented in 19 interlinked processes, 15 related procedures and 24 working instructions. All these materials, along with the quality policy, the mission, the strategies and the values were made publicly available. Based on the measurable indicators developed to monitor some of the processes, areas of weakness of the system were objectively identified and consequently QI actions implemented. The appropriateness of all this allowed the programme to finally achieve an official ISO 9000:2001 certification.The application of the ISO 9001:2000 standard served to develop an internal QA and QI system and to meet most of the standards developed for QA in higher and medical education.

In our study we have developed an HPLC-ESI-MS/MS method for qualitative and quantitative analysis of underivatized amino acids on dry blood spots. The sensitive and specific instrumental performances permitted the chromatographic separation of 40 amino acids and their isomers within 10 min. The method has been set up for cases of suspected metabolic diseases revealed by newborn screening. What is new is that it is applied on the same blood spots used for newborn screening, instead of plasma, in order to avoid involvement of doctors, increased anxiety for parents, stress for patients for plasma collection, long time of waiting and further costs for analysis.

Background: Asthmatic patients have high exhaled nitric oxide (NO) levels. NO-mediated inflammatory actions are mainly due to NO conversion into reactive nitrogen species, which can lead to nitrotyrosine formation. The aim of this study was to assess 3-nitrotyrosine (3-NT) levels in exhaled breath condensate (EBC) of asthmatic and healthy children and to investigate whether there is any relationship with exhaled NO (FENO) and lung function. Methods: The study included 20 asthmatic children (10 steroid-naive with intermittent asthma, 10 steroid-treated with unstable persistent asthma) and 18 healthy controls. They underwent FENO measurement, EBC collection and spirometry. 3-NT was measured by a new liquid chromatography–tandem mass spectrometry (LC-MS/MS) method in isotopic dilution. Results: The median EBC concentration of 3-NT (expressed as nitrotyrosine/tyrosine ratio × 100) in asthmatic children was fivefold higher than in healthy subjects [0.23% (0.12–0.32) vs 0.04% (0.02–0.06), P

The Bispectral Index (BIS) is a system used to measure sedation levels. Some investigators recently analyzed changes in the BIS during natural sleep in adults and found that the BIS diminished considerably as sleep became deeper. No such studies have been undertaken to investigate changes in the BIS in sleeping children. The aim of this work was to assess the trend of the BIS in the various stages of sleep in a group of children, performing a descriptive analysis on a limited number of cases. We evaluated 15 children with negative clinical findings and a normal electroencephalogram (EEG) as part of their follow-up for prior episodes of epilepsy, recording the BIS and EEG in a waking state, in the various stages of sleep and on reawaking. For each stage, the mean value, the standard deviation, and the range of BIS values were calculated. The results showed that the BIS decreased progressively as sleep became deeper. The correlation between the stage of sleep and the BIS was significant. On reawaking, a slow increase was apparent in the BIS.

Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, may be associated with long-term airflow limitation. Survivors of BPD may develop asthma-like symptoms in childhood, with a variable response to beta(2)-agonists. However, the pathologic pathways underlying these respiratory manifestations are still unknown. The aim of this study was to measure exhaled nitric oxide (FE(NO)) and lung function in a group of 31 school-age survivors of BPD. They showed variable degrees of airflow obstruction (mean FEV(1) 77.8 +/- 2.3% predicted) unresponsive to beta(2)-agonists in 72% of the subjects. Their FE(NO) values (geometric mean [95% confidence interval]: 7.7 [+/- 1.1] ppb) were significantly lower than in a group of healthy matched control subjects born at term (10.7 [+/- 1.1] ppb, p0.05) and a group of preterm children without BPD (9.9 [+/- 1.1] ppb, p0.05). The children with BPD were also compared with a group of 31 patients with asthma with a comparable airflow limitation (FEV(1) 80.2 +/- 2.1% predicted) and showed FE(NO) values four times lower than in those with asthma (24.9 [+/- 1.2] ppb, p0.001). In conclusion, unlike children with asthma, school-age survivors of BPD have airflow limitation associated with low FE(NO) values and lack of reversibility to beta(2)-agonists, probably as a result of mechanisms related to early life structural changes in the airways.

Background Hunter syndrome, mucopolysaccharidosis type II (MPS II), is a X-linked inherited disorder caused by the deficiency of the enzyme iduronate-2-sulfatase (IDS), involved in the lysosomal catabolism of the glycosaminoglycans (GAG) dermatan and heparan sulfate. Such a deficiency leads to the intracellular accumulation of undegraded GAG and eventually to a progressive severe clinical pattern. Many attempts have been made in the last two to three decades to identify possible therapeutic strategies for the disorder, including gene therapy and somatic cell therapy. Methods In this study we evaluated the intraperitoneal implantation of allogeneic myoblasts over-expressing IDS, enclosed in alginate microcapsules, in the MPS II mouse model. Animals were monitored for 8 weeks post-implantation, during which plasma and tissue IDS levels, as well as tissue and urinary GAG contents, were measured. Results and conclusions Induced enzyme activity occurred both in the plasma and in the different tissues analyzed. A significant decrease in urinary undegraded GAG between the fourth and the sixth week of treatment was observed. Moreover, a biochemical reduction of GAG deposits was measured 8 weeks after treatment in the liver and kidney, on average 30 and 38%, respectively, while in the spleen GAG levels were almost normalized. Finally, the therapeutic effect was confirmed by histolochemical examination of the same tissues. Such effects were obtained following implantation of about 1.5 × 106 recombinant cells/animal. Taken together, these results represent a clear evidence of the therapeutic efficacy of this strategy in the MPS II mouse model, and encourage further evaluation of this approach for potential treatment of human beings. Copyright © 2005 John Wiley & Sons, Ltd.

Objective Pharmacokinetic studies have shown that the biological effect of triamcinolone acetonide (TA) is equivalent to that of triamcinolone hexacetonide (TH), if used at double the dosage. In this study we compared the efficacy of intra-articular TA at a dose twice that of TH in symmetrically involved joints, in children with juvenile idiopathic arthritis (JIA). Method Children with active arthritis and a similar degree of inflammation in two symmetrical joints were enrolled in the study. The symmetry was assessed by both clinical examination and synovial fluid analysis. The dose given was 1 mg/kg up to 40 mg of TH or 2.0 mg/kg up to 80 mg of TA. The identity of injected compound was blinded to the patient and to the physician. Results Thirty-seven patients, 30 female, seven male, with JIA, entered the study. A total of 86 joints were injected. Twenty-one (53.8%) of the joints injected with TA relapsed first compared with only six (15.4%) of the joints injected with TH. In three (7.7%) relapse occurred simultaneously. Nine (23%) were still in remission after 24-month follow-up. The percentage of joints with lasting remission was higher with TH than with TA (80 vs 47.5% after 12 months and 63.6 vs 32.4% after 24 months, respectively; log rank test P = 0.003). Conclusion Even when TA is given at higher doses, TH is more effective and should be considered the drug of choice for intra-articular treatment of JIA.

Objective. We analysed our experience with the use of iloprost for the treatment of critical ischaemic digits (ID) in children with connective tissue diseases (CTD) in order to assess its safety and efficacy. Methods. This was a retrospective analysis of paediatric patients with CTD who were treated with iloprost for critical ID resistant to conventional therapy. Information on demographics, clinical and laboratory features, the regimen of iloprost treatment and outcome were collected. Results. Fifteen patients (10 female, five male) treated one or more times with iloprost were included (total of 19 treatments). Six had juvenile systemic sclerosis, five had systemic lupus erythematosus, three had mixed connective tissue disease and one had cutaneous polyarteritis nodosa. Thirteen patients were already taking calcium channel blockers with no improvement; in two patients ID were the presenting signs of the disease without prior treatment. Eleven patients had more than two fingers involved; one child had involvement of all 10 fingers. Normal digital blood flow was achieved in 74% of treatments and significant improvement was noted in 26%. Fingertip necrosis was present in 11 patients (14 treatments). It healed completely in seven, improved in one and remained unchanged in six. Raynaud’s phenomenon (RP) was present in 14 patients (17 treatments): in two no RP attack occurred during the follow-up period, eight improved both in the number of attacks per week and in the duration of each attack. Complete pain relief was observed in 10/17 treatments (59%) and there was a significant decrease in pain in the remaining seven. No major side-effects or withdrawal symptoms were reported. Minor side-effects reported include reversible headache (seven patients), hypotension or irritability (three), nausea/vomiting (two) and injection site reaction (one). Conclusions. Iloprost appears to be a safe and effective treatment for ischaemic digits and digital ulcers in children with CTD. In conjunction with immunosuppressive drugs, it has a potential role in preventing irreversible complications, such as digital gangrene and amputation.

Background: Cysteinyl leukotrienes (Cys-LTs) and isoprostanes are inflammatory metabolites derived from arachidonic acid whose levels are increased in the airways of asthmatic patients. Isoprostanes are relatively stable and specific for lipid peroxidation, which makes them potentially reliable biomarkers for oxidative stress. A study was undertaken to evaluate the effect of a course of oral steroids on Cys-LT and 8-isoprostane levels in exhaled breath condensate of children with an asthma exacerbation. Methods: Exhaled breath condensate was collected and fractional exhaled nitric oxide (FENO) and spirometric parameters were measured before and after a 5 day course of oral prednisone (1 mg/kg/day) in 15 asthmatic children with an asthma exacerbation. Cys-LT and 8-isoprostane concentrations were measured using an enzyme immunoassay. FENO was measured using a chemiluminescence analyser. Exhaled breath condensate was also collected from 10 healthy children. Results: Before prednisone treatment both Cys-LT and 8-isoprostane concentrations were higher in asthmatic subjects (Cys-LTs, 12.7 pg/ml (IQR 5.4–15.6); 8-isoprostane, 12.0 pg/ml (9.4–29.5)) than in healthy children (Cys-LTs, 4.3 pg/ml (2.0–5.7), p=0.002; 8-isoprostane, 2.6 pg/ml (2.1–3.0), p

Fractional exhaled nitric oxide (FE(NO)) and exhaled carbon monoxide (ECO) have been proposed as markers of airway inflammation and oxidative stress.The aim of this study was to assess the effect of oral prednisone treatment on FE(NO) and ECO levels in a group of 30 asthmatic children with asthma exacerbation.Thirty asthmatic children with asthma exacerbation were treated with oral prednisone for 5 days (1 mg/kg/day). Before and after prednisone therapy, ECO was measured by means of a chemical analyzer and FE(NO) was measured by means of a chemiluminescence analyzer. ECO and FE(NO) were also measured in a group of healthy nonatopic children.Before therapy, both ECO values and FE(NO) values were higher in asthmatic children (ECO, 3.2 +/- 0.2 ppm; FE(NO) online, 74.9 +/- 6.2 ppb; FE(NO) offline, 20.2 +/- 1.4 ppb) than in healthy controls (ECO, 2.0 +/- 0.2 ppm [P.01]; FE(NO) online, 10.1 +/- 0.8 [P.0001]; FE(NO) offline, 5.9 +/- 0.4 ppb [P.0001]). An overlap in ECO values was found between healthy controls and asthmatic children. After prednisone therapy, there was a significant reduction in FE(NO) values (FE(NO) online, 40.6 +/- 4.6 ppb [P.0001]; FE(NO) offline, 11.1 +/- 0.8 ppb [P0.0001]) and a slight but nonsignificant decrease in ECO values (2.7 +/- 0.2 ppm [P = not significant]) in the asthmatic group. No significant correlation between ECO values and FE(NO) values was found in either the asthmatic children or the controls.After a course of prednisone therapy, in children with asthma exacerbation there is a significant decrease in FE(NO) but no significant change in ECO levels. This possibly suggests that ECO is less sensitive than FE(NO) to inhibition by corticosteroids.

The objective of this investigation was to determine the prevalence of Cx26 mutations in familial and sporadic cases of non-syndromic preverbal hearing impairment (HI). Molecular analysis of the Co...

NO is increased in exhaled air of asthmatic patients, and may be used as a marker of airway inflammation. The online method is a standardized technique for measuring exhaled nitric oxide (ENO). However, this method has proven difficult for some children, who may have trouble maintaining a constant expiratory flow. The aim of this study was to validate a modified technique for online ENO measurement that utilizes a flow regulator to overcome the patient problem of having to actively maintain a constant expiratory flow. We measured ENO levels with two methods in 105 asthmatic and 10 healthy subjects, comparing the standardized (ST) single-breath method with a modified single-breath, flow-driven (FD) method. With the ST method and visual monitoring, the subjects inhaled NO-free air to TLC, and exhaled with a target flow of 50 ml/s. With the FD method, the subjects exhaled from TLC and flow was kept constant (50 ml/s) by the operator, using a flow regulator. The subjects were divided into two groups, one consisting of children aged 4 to 8 yr (n = 74) and the other of children aged 9 to 16 yr (n = 41). In the group aged 4 to 8 yr, 38 children (51%) were unable to perform the ST method, whereas only five children (7%) failed to perform the FD technique. In the group aged 9 to 16 yr, only four children (10%) were unable to perform the ST maneuver, and all successfully performed the FD maneuver. The mean concentrations of ENO in the 73 children who performed both types of maneuver were similar (36.1 +/- 3.4 [mean +/- SEM] ppb with the ST method and 33.8 +/- 3.3 ppb with the FD technique, p = NS) and were highly correlated with one another (r = 0.99, p0.0001). ENO values were significantly higher in steroid-naive than in steroid-treated asthmatic children. In conclusion, we describe a modified online method for measuring ENO that is simple, does not require active cooperation to maintain a constant expiratory flow, and can be easily performed by children from 4 to 5 yr of age onward.

Human parvovirus B19 is considered an etiologic agent of aplastic anemia in immunosuppressed patients. Microscopic vasculitis, with or without renal involvement, has recently been attributed to this viral infection in immunocompetent patients. This study describes four cases of thrombotic renal graft microangiopathy presumably secondary to B19 infection. Twelve to 50 days after transplantation, four patients presented a renal graft dysfunction with creatinine rising to 360 to 1088 micromol/L and requiring hemodialysis in three cases. Renal involvement appeared after a systemic illness characterized by fever, fatigue and arthralgia, aplastic anemia (hemoglobin ranged from 5.3 to 7.8 g/dl), and thrombocytopenia. A thrombotic microangiopathy was observed in the renal biopsies, and the parvovirus B19 genome was isolated by PCR from the specimens. All four patients also became IgM-positive for parvovirus. Three of the four renal biopsies taken at the time of transplantation (T0) from the same patients were found positive for the B19 genome. Graft function recovered, with resolution of the aplastic anemia, within 22 to 110 d. Twenty biopsies performed as routine controls or for suspected acute rejection and nine T0 biopsies of patients with no signs of B19 infection were used. The B19 genome was found in two of 20 posttransplant biopsies and in one of nine T0 biopsies. The temporal association between aplastic anemia and the onset of thrombotic graft microangiopathy, isolation of the viral genome in renal specimens, seroconversion, and endothelial tropism of the virus suggests that B19 could be the etiologic agent of thrombotic microangiopathy in these cases. The development of the disease after infection could depend on other detrimental cofactors, which make the patient more susceptible to microthrombi formation in the renal microvasculature. The renal graft could represent the route of B19 transmission.

Recently many studies have focused on long-term follow-up of phenylketonuria (PKU McKusick 261600) patients, especially regarding discontinuation of diet in adulthood and subsequent possible neurological involvement. Neurological symptoms have been observed in some patients after discontinuation of diet, with improvements after reintroduction of a phenylalanine-restricted diet (Pietz et al 1998). Brain magnetic resonance imaging (MRI) revealed white-matter abnormalities in patients with neurological impairment but also in many patients without neurological symptoms (Burgard et al 1999). Myelin changes observed by brain MRI are similar in early-treated, late-treated and untreated patients, differing only in extension. Neurological investigations of treated adult PKU patients revealed minor neurological signs (tremor, brisk deep tendon reflexes, clumsy motor coordination) indicating the possibility of a specific neurological syndrome in adult PKU patients off diet. Even early-treated phenylketonuric patients show subtle symptoms of CNS damage, in addition to neuropsychological, neurophysiological and brain imaging abnormalities (Pietz et al 1998). Therefore, further investigations are necessary to evaluate the presence of biochemical changes, even in early-treated patients, that could be implicated in the neurological alterations. The aim of our study was to investigate dopamine and serotonin metabolism (homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA), respectively) in early-treated PKU patients with white-matter abnormalities on magnetic resonance imaging.

Background. The aims of our study were twofold. First, we sought to evaluate in symptomatic children the influence of the Helicobacter pylori genotype on gastritis, abdominal pain, and circulating anti–H. pylori IgG antibodies (anti–H. pylori IgG) or pepsinogen A (PGA) and C (PGC). Additionally, we sought to assess anti–H. pylori IgG, PGA, and PGC patterns in a large cohort (N = 921) of asymptomatic children. Materials and Methods. In 183 symptomatic children, H. pylori infection and the presence of gastritis were evaluated by histology. In a subgroup of 20 H. pylori–positive children, the H. pylori genotype was evaluated also by polymerase chain reaction. Nine hundred and twenty-one asymptomatic children, aged 11 to 14 years, were studied by anti–H. pylori IgG, PGA, and PGC serum determination. Results. The infection was found in 33 of 183 symptomatic children; among the 20 H. pylori–positive children for which the H. pylori genotype was available, cagA was present or absent in equal percentages. H. pylori infection was associated with more severe gastritis and higher serum levels of anti–H. pylori IgG and PGC but not with abdominal pain. In infected children, higher levels of anti–H. pylori IgG and the presence of abdominal pain were associated with infections caused by cagA-positive strains. In the cohort of 921 asymptomatic children, raised levels of anti–H. pylori IgG, PGA, and PGC were found in approximately 5% of the cases. Conclusions. Infection with cagA-positive H. pylori strains can be associated with increased frequency of reported abdominal pain and higher circulating levels of anti–H. pylori IgG. The serological assessment of H. pylori IgG using H. pylori antigens containing significant amounts of cagA protein may, therefore, underestimate the true prevalence of infection.

Before being considered for a cystic fibrosis (CF) gene therapy trial, any gene delivery agent must be able to show that it produces low levels of toxicity as well as being able to protect the DNA from nuclease degradation. Here we show that complexes of linear polyethylenimine (L-PEI) and DNA can repeatedly be administered to animals (up to 21 consecutive days) without eliciting an immune response against PEI/DNA particles or inducing toxic side effects due to accumulation of PEI in the lungs. However, the host response to the exogenous protein resulted in some decrease of expression. PEI-mediated transfection was unaffected by treatment of the complexes with DNase (frequently used to reduce the viscosity of lung secretions in CF patients). Taken together, these properties make L-PEI a valuable vector for gene therapy of CF.

Nitric oxide (NO) can be detected in human exhaled air, and its endogenous production is increased in patients with asthma. It may provide a noninvasive means for measuring airway inflammation. The aim of this study was to establish reference values for exhaled NO concentrations in a large number of healthy school-age children. We measured exhaled NO levels in 159 white healthy children (88 girls, 71 boys, age range 6-15 years) recruited from two public schools of Padua, Italy. Exhaled NO levels in exhaled gas were measured by a tidal breathing method with a chemiluminescence analyzer, and NO steady-state levels were recorded. Nasal NO levels were measured by direct sampling from the nose during mouth breathing. The mean concentration of endogenous NO in orally exhaled gas was 8.7 parts per billion (ppb) (95% confidence interval (C.I.), 8.1-9.2 ppb) and sampled data followed a log-normal distribution (Kolmogorov-Smirnov d = 0.77, P > 0.2). No difference was found between boys (mean value, 8.4 ppb; 95% C.I., 7.3-9.4 ppb) and girls (mean value, 8.9 ppb; 95% C.I., 7.9-9.9 ppb). No significant correlation was found between age, height, or spirometric data and exhaled NO levels (r < 0.2). The mean value of nasal NO concentrations was 216 ppb (95% C.I., 204-228 ppb). There was no correlation between exhaled and nasal NO values (r = 0.16, P = ns). In conclusion, this study establishes a reference range for exhaled NO values measured by a tidal breathing method in children between age 6-15 years. The observed levels are independent of age, gender, and lung function, and can be used to monitor airway inflammation in asthmatic children.

Exhaled nitiric oxide (NO) is increased in exhaled breath of asthmatic patients. The aim of this study was to investigate the longitudinal changes of exhaled NO outside and during the pollen season in pollen-allergic asthmatic children. Twenty-one children (age 6 to 16 yr), with a seasonal allergic asthma sensitive to grass pollen, underwent measurements of exhaled NO and pulmonary function before (March), during (May), and after (November) the pollen season. Exhaled NO was measured by a tidal breathing method with a chemiluminescence analyzer and NO steady-state levels were recorded. The timing of the measurements during the pollen season was based on the atmospheric pollen count. Exhaled NO values of asthmatic children were compared with those of 21 sex- and age-matched healthy children. Pulmonary function and symptoms of asthma were also evaluated at each visit. The mean value of exhaled NO before the grass season was 12.7 ± 5.1 ppb (mean ± SD), significantly higher when compared with controls (7.8 ± 2...

It has been hypothesized that concentrations of exhaled nitric oxide (NO) may be related to the extent of cytokine-mediated airway inflammation. Recent findings indicate the nasal airways as an important site of NO production. Our objective was to evaluate whether children with allergic rhinitis show different nasal NO levels when compared with normal healthy subjects and the effect of topical steroids and anti-histamine therapy. We have measured the concentration of NO drawn from the nose of 21 children (5-17 years old) affected by perennial allergic rhinitis (house dust mite) out of therapy for at least 3 weeks. Thirteen children were then treated with nasal beclomethasone dipropionate (BDP) (400 micrograms daily) and eight subjects with nasal anti-histamine levocabastine (200 micrograms daily). Measurements were performed before and after 10 days of treatment. As a control group we evaluated 21 healthy children aged 5-15 years. To measure NO we used a chemiluminescence analyser. Before treatment the whole group of children with allergic rhinitis showed a mean (+/- SEM) nasal NO concentration of 267 +/- 18 ppb, significantly higher (P < 0.01) than the control group (186 +/- 15 ppb). The group of children treated with BDP showed, after 10 days of therapy, a significant (P < 0.05) decrease of nasal NO concentration (271 +/- 21 ppb vs. 212 +/- 20 ppb). Indeed, in the group treated with levocabastine, nasal NO concentrations did not present a significant difference (P not significant) compared with baseline (261 +/- 33 ppb and 252 +/- 31 ppb, respectively). These data suggest that (1) children with allergic rhinitis have higher levels of nasal NO than non-atopic controls and (2) intranasal steroid therapy significantly reduces nasal NO production in children with allergic rhinitis. We speculate that the allergic inflammatory response may influence the nasal NO levels and that NO measurements may be a useful marker of nasal inflammation.

We followed the clinical course of 21 infants with bronchopulmonary dysplasia enrolled in a prospective home O2 therapy programme during a 4-year-period. Mean gestational age was 28.5 weeks (range, 25–36 weeks) and mean birth weight 1093 g (range 630–2750 g). Infants were regularly monitored to maintain pulse oximeter O2 saturation over 94%–95%. The source of O2 was liquid oxygen and was delivered by nasal cannula. During the follow up oxygenation was assessed by SatO2 measurement, cardiac function by Doppler echocardiography and respiratory function by the occlusion technique. All patients had an ophthalmological follow up. The mean age of the infants at discharge was 3.7 months (range 1.7–8.6) and mean weight 2830 g (range 2150–3780 g). At discharge 8 infants had right ventricular hypertrophy (RVH) and four of them had pulmonary hypertension. Mean duration of home O2 therapy was 97 days (range 15–320 days) and the mean age of discontinuation of O2 was 6.9 months (range 3–14.7 months). The cardiological follow up was benign: the ECG signs of RVH disappeared by 12 months of age in six out of eight infants and the right ventricular pulmonary pressure, as measured by the Doppler method, normalised in the four patients in whom it was detected. No relationship was found between respiratory mechanics and the duration of O2 therapy. Weight gain was poor with mean growth at the 3rd percentile for females and just below the 3rd percentile for males. Twelve of the 21 infants required 25 rehospitalizations. No one presented deterioration of retinopathy of prematurity that was present in 16 infants at discharge; at 12 months retinopathy was resolved in 14 infants. A total of 2025 hospital days were saved, representing a significant financial saving. Conclusion Home O2 therapy permits the safe early discharge of O2-dependent BPD infants and it reduces significantly the length of time spent in hospital which represents a considerable financial saving.

Recently, it has been demonstrated that paranasal sinuses are an important site of nitric oxide (NO) production in the upper airways. The aim of this study was to evaluate the NO nasal concentration in children with acute maxillary sinusitis before and after treatment with antibiotic therapy. We performed NO nasal measurements in 16 children 4 to 13 yr of age with acute maxillary sinusitis and compared values with 16 age- and sex-matched healthy control subjects. The diagnosis of acute sinusitis was done by clinical signs and symptoms in addition to radiographic examination. NO nasal concentrations were measured by a chemiluminescence analyzer. Nasal NO steady state during oral breathing was recorded. The mean +/- SEM NO nasal concentration in children with sinusitis was 70 +/- 8.7 parts per billion (ppb) and increased significantly to 220 +/- 15 ppb (p0.001) after antibiotic therapy (amoxicillin/clavulanate). NO values after recovery from sinusitis were similar to those of healthy control subjects (245 +/- 15 ppb, p = NS). NO nasal measurements were also performed before and after antibiotic treatment in nine children 4 to 12 yr of age with symptoms of upper respiratory tract infection but no symptoms of sinusitis. In these children NO nasal levels were 249 +/- 32 ppb and did not change (p = NS) after antibiotic therapy. We conclude that during acute maxillary sinusitis the concentration of nasal NO is largely decreased, probably because of an impaired flow of NO from the paranasal sinuses, and that NO returns to normal levels after antibiotic therapy.

In the present era of resource management, there is increasing emphasis on the need to make the best possible use of available resources. We therefore measured the productive factors directly involved in performance of 59 evoked potential examinations (brainstem auditory evoked potentials, BAEPs; flash visual evoked potentials, F-VEPs; and electroretinograms, ERGs) in different pediatric age groups. In order to ascertain the gap between the costs of instrumental examinations performed in our service on children and the fees reimbursed by the Italian national health service (NHS) a breakdown was made of the costs of tests and their scheduling in relation to the different age variables involved. It was found that the fees reimbursed do not cover the real costs, because they underestimate the actual consumption of resources. The findings recorded indicate that for pediatric tests the economic audit should be graded according to the ages of the children examined and should include an analysis of different test phases. The economic audit should also be considered a preliminary step in clinical audit. It is concluded that it is financially punitive to reimburse a pediatric service with a fee based on the examination of adults, because in pediatrics the variable ``age'' influences the duration and complexity of tests and also their interpretation.

Lipolysis has been measured in humans by means of stable isotope techniques using labeled palmitic acid (PA) or glycerol as tracers. If other fatty acids (FA) such as linoleic acid (LLA) have the same rate of appearance (R(a)) as PA and therefore contribute equally to oxidative and nonoxidative metabolism is unknown. We infused albumin-bound [U-C-13]PA and [U-C-13]LLA in seven critically ill infants (weight 3.6 +/- 1.3 kg, age 57 +/- 64 d) receiving 20.9 +/- 5.4 kcal . kg(-1). d(-1) of i.v. glucose only, and measured simultaneously the R(a) of PA and LLA from the isotopic enrichment of plasma FFA by mass spectrometry. A needle biopsy of the s.c. adipose tissue was obtained for FA composition. PA in adipose tissue was higher than LLA (40 +/- 6.7 versus 5.4 +/- 3.2 mol %, p

To evaluate the physiologic course of pulmonary function in infants with bronchopulmonary dysplasia (BPD) weighing less than 1,250 g at birth, 24 infants with BPD underwent serial pulmonary function evaluations from birth until 2 yr of age. All infants were intubated at birth and the mean duration of mechanical ventilation was 38 +/- 4 d. Passive respiratory system compliance (Crs) and resistance (Rrs) were measured between 10 and 20 d of life during mechanical ventilation. Thereafter pulmonary mechanics and functional residual capacity (FRC) were evaluated at 3, 6, 9, 12, and 24 mo of postnatal age. Forced expiratory flow (Vmax,FRC) was measured at 2 yr of age. A severe alteration on Crs (50% of predicted) was found during the acute phase of BPD, associated with abnormal values of Rrs. A progressive improvement (ANOVA, p < 0.0001) occurred in the first year of life and, at 24 mo of age, Crs and Rrs reached the range of normalcy. FRC value was 86 +/- 7.5% of predicted at 3 mo and gradually increased to a mean value of 115 +/- 5% of predicted at 2 yr of age. In spite of the good resistance time course over the 2-yr evaluation, less favorable data of Vmax,FRC were found with individual values reduced more than 40% of predicted values in 70% of the children. In conclusion, although pulmonary mechanics of BPD survivors improves during the first years of life, reaching the range of normal values, at 2 yr of age they still present a substantial airway function impairment as revealed by the low forced expiratory flows.

We report on a new case of FRAXE mutation identified through the screening of a population of FRAXA-negative mentally retarded individuals. The index case, a 4-year-old boy with distinct minor anomalies and mental retardation with severe verbal impairment, his older brother, referred to as normal, and the mother have undergone careful clinical and molecular evaluation. The molecular defect, characterized by standard Southern blot analysis, is represented by a hypermethylated {open_quotes}full mutation{close_quotes} in the 2 boys and by a unique, altered, presumably unmethylated, band in the mother, which is interpreted as a {open_quotes}premutation.{close_quotes} The cytogenetic analysis failed to detect a folate-sensitive Xq27-28 fragile site in either {open_quotes}fully mutated{close_quotes} individual. The phenotype and intellectual performance of the 15-year-old brother of the propositus appeared completely normal. Our propositus shares some traits with previously described FRAXE-mutated subjects, suggesting an association with the Xq28 molecular defect; nevertheless, we find it difficult to reconcile the molecular identity and phenotypic difference in these mutated members of the same family. This could be a case of extreme phenotypic variability or a result of a more complicated molecular mechanism. 11 refs., 4 figs.

Nasal nitric oxide levels are low in patients with primary ciliary dyskinesia, but it is not known whether this defect is already present in the first months of life. The current authors measured nasal nitric oxide in two infants with situs inversus and primary ciliary dyskinesia, diagnosed by electron microscopy at 4 and 6 months of age, and in five healthy control infants. Nasal nitric oxide values in the primary ciliary dyskinesia infants (85 and 115 parts per billion (ppb)) were markedly lower than in the healthy controls (mean: 295 ppb, range: 225-379 ppb). This is the first report to show that nasal nitric oxide values are already low in early life in primary ciliary dyskinesia children, supporting the hypothesis that a reduced production of nasal nitric oxide is an intrinsic feature of this disease. The current authors suggest that the nasal nitric oxide test may be a useful, noninvasive method for screening young children for primary ciliary dyskinesia in clinical practice.

Background: Exhaled breath condensate (EBC) is a rapidly expanding area of research to study airway inflammation through the detection of volatile and non-volatile substances in the airways. Aims: To determine the safety and feasibility of EBC procedure in a group of children with asthma of varying severity. Methods: In a cross sectional study of children aged 4‐17 years, 18 healthy and 91 asthmatic children (69 in stable condition and 22 with asthma exacerbation) underwent the EBC procedure. Outcomes assessed included completion of the procedure, decrease in FEV1, change in fractional exhaled nitric oxide (FENO), and adverse effects. No pretreatment with β2 agonists was given. All children were able to successfully complete the EBC procedure. Results: Median fall in FEV1 after the procedure was -1% (IQR -3.5, 1.8) in asthmatics and was comparable to that observed in healthy children. In only one asthmatic child did the drop in FEV1 exceed 12%. No significant changes in FENO were observed after EBC. Conclusion: This study suggests that EBC is a simple and well tolerated method for evaluating biological samples from the lower airway. The procedure was safe in children with asthma exacerbation, and the success rate was 100% in children aged 4 years and above.

The replication defective retrovirus, pXM5(N2), was used for an easy, safe and reproducible test for the screening of furocoumarins with antiretroviral activity. High titer viral supernatants have been photomodified by UVA light (20 kJ m −2 ) in the presence of different concentrations of two psolarens (8-methoxypsoralen, 8-MOP and 4,5′,8-trimethylpsoralen, TMP) and one angelicin (4,6,4′-trimethylangelicin, TMA). At low concentrations (100–250 ng ml −1 ) 8-MOP and TMA did not show any significant antiviral activity, while TMP demonstrated a reduction of virus infectivity by one log at 250 ng ml −1 . At the highest concentration (5 μg ml −1 ), TMA and TMP reduced the virus titer by one and more than two logs, respectively, being, therefore, two and four times more active than 8-MOP. The most active compound, TMP, was further tested on HIV-1 viral supernatants. Total inactivation of the HIV-1 (200 SFU) was obtained in the presence of 1 μg ml −1 of TMP and 20 kJ m −2 of UVA light. Our results support the validity of the N2 system to detect the antiretroviral activity of furocoumarins and suggest the potential of TMP in combination with UVA light against HIV-1.

There is little information on bone turnover in asthmatic children taking long-term treatment with inhaled steroids (ICS). The aim of this longitudinal study was to determine the effects of inhaled beclomethasone dipropionate (BDP) on bone mineral density (BMD), in asthmatic children treated over a period of six months. BMD and growth were studied in two age- and sex-matched groups of asthmatic children. These comprised: 14 asthmatic children (Group 1) who had taken BDP in a dosage of 300-400 micrograms daily through a 145 ml spacer device for at least 6 months (mean age 9.1 yrs); and a control group of 16 age- and sex-matched asthmatic patients (Group 2) not treated with ICS (mean age 9.5 yrs). Mean duration of asthma was 5.7 yrs in Group 1 and 5.5 yrs in Group 2. Vertebral BMD (L2-L4) was measured by dual energy X-ray absorptiometry (DEXA) at the beginning (baseline) of the study and 6 months later. There were no significant differences in the baseline bone mass (mean +/- SEM) between the two groups (0.63 +/- 0.03 and 0.64 +/- 0.02 g.cm-2 in Group 1 and 2, respectively). During the observation period, bone density increased, by 4% (95% confidence interval (95% CI) 2-6) in the control group and by 2.3% (95% CI 0.4-4.2) in the group under BDP treatment, showing no significant influence of the treatment. No difference was found in height velocity evaluated before starting BDP and after 6 months of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

A large number of very-low-birth weight infants are fed formulas containing medium-chain triglycerides (MCT) to enhance fat and calcium absorption. Studies are available on the intestinal absorption of MCT, which is nearly complete, but uncertainties exist on the metabolic fate of octanoic acid, the major component of MCT. Oxidation accounts for approximately 50% of the dietary intake, and losses as dicarboxylic acids in the urine are negligible. Since storage in adipose tissue is limited, conversion into long-chain fatty acids (LCFA) is likely to be an important route. To study the nonoxidative metabolism of MCT, six preterm infants fed a standard premature formula containing 38 weight% (wt%) MCT (54 mol% medium-chain fatty acids (MCFA), of which 35 mol% is octanoic acid) were studied at 4 weeks of age, when on full oral intake and receiving on average 130 kcal/kg/d. The study consisted of an oral primed constant-rate infusion of [13C]-octanoate and the measurement of the 13C enrichment of individual fatty acids in plasma triglycerides (TG) by a highly sensitive on-line combustion method using gas chromatography-isotope ratio mass spectrometry (GC-IRMS). We observed a significant incorporation of the dietary [13C]-octanoic acid in plasma TG (10.0% +/- 4.5% of the enrichment of the diet). A noticeable incorporation of the label was detected in myristic and palmitic acids (4.6% +/- 2.5% and 7.8% +/- 4.1% of the octanoic enrichment of the diet). The absolute amount of the fatty acids was studied with conventional GC, and the plasma TG fatty acid profile differed markedly from the diet.(ABSTRACT TRUNCATED AT 250 WORDS)

We have developed a simple rapid DNA screening test that allows us simultaneously to analyze seven CF mutations (delta F508, R347P, S549N, G551D, R553X, R334W, 444delA) that together account for about 60% of all CF mutations in the Italian population. It consists of three steps: multiplex polymerase chain reaction (PCR) amplification of exons 4, 7, 10 and 11; restriction endonuclease digestion of the PCR products; and vertical polyacrylamide gel electrophoresis analysis. We have used our multiplex assay for analyzing 15 CF chromosomes (non delta F508) and have found 3 cases of the R553X mutation; the latter have been confirmed by amplification and digestion of exon 11.

A sensitive and accurate assay was developed for the measurement of 8-methoxypsoralen in plasma using electron-impact positive-ion mass fragmentography. 4,5,8-Trimethylpsoralen was used as an internal standard. Sample preparation consisted of a two-step liquid phase extraction using acetonitrile and methylene chloride. The calibration curve showed a linear relationship between the peak areas of 8-methoxypsoralen and 4,5,8-trimethylpsoralen over a wide range of 8-methoxypsoralen concentrations (1–500 ng/ml). Within- and between-run precisions, measured at five different drug concentrations, varied from 0.82 to 1.41% and from 0.82 to 1.86%, respectively.

Background Lysosomal storage disorders (LSDs) are pathologies caused by the deficit of lysosomal enzymes; late diagnosis may render therapeutic programs less effective. As early, pre-symptomatic detection could change the natural history of the disease, we are setting up rapid microassays using dried blood spots (DBS) on filter paper. Here we report α-glucosidase and β-galactosidase assays. Methods Enzymatic activities were evaluated on DBS from five different groups of subjects including healthy controls and patients affected with an LSD. A 260-day monitoring of DBS preservation at five different temperatures and a comparison of the enzymatic activities measured in DBS obtained from a single (sDBS) or a double (dDBS) blood drop were performed as well. Results Both assays could clearly distinguish the affected patients from the other subjects analyzed. Storage of DBS at 4 °C and below allowed a longer preservation of the enzymatic activities. No significant differences were detected between sDBS and dDBS. Conclusions DBS can be used for non-invasive, easy, inexpensive lysosomal enzyme assays. Reliability of assays on DBS needs to be checked using a control enzyme such as β-galactosidase. DBS can be still reliably analyzed even if generated incidentally by two overlapped drops.

In many fields of medicine there is a growing interest in characterizing diseases at molecular level with a view to developing an individually tailored therapeutic approach. Metabolomics is a novel area that promises to contribute significantly to the characterization of various disease phenotypes and to the identification of personal metabolic features that can predict response to therapies. Based on analytical platforms such as mass spectrometry or NMR-based spectroscopy, the metabolomic approach enables a comprehensive overview of the metabolites, leading to the characterization of the metabolic fingerprint of a given sample. These metabolic fingerprints can then be used to distinguish between different disease phenotypes and to predict a drug's effectiveness and/or toxicity. Several studies published in the last few years applied the metabolomic approach in the field of pediatric medicine. Being a highly informative technique that can be used on samples collected noninvasively (e.g. urine or exhaled breath condensate), metabolomics has appeal for the study of pediatric diseases. Here we present and discuss the pediatric clinical studies that have taken the metabolomic approach., JRC.DDG.I.6-Systems toxicology

Thirty-six children (age range, 18-30 months) born to HIV-1-infected mothers were studied for speech development by matching 18 infected with 18 non-infected subjects for age, sex and socioeconomic status. All the children were in good health. Each child was given three comprehension and three production tasks. In addition, each child's mean length of utterance (MLU) was obtained by observation of natural child-parent interactions. The development quotients (DQ) were assessed by Brunet-Lézine's tests. Infection significantly affected children's MLU, the infected children being less advanced than those non-infected. Both infected and non-infected children progressed in language acquisition from the second to the third year of age, but infected children had significantly greater production difficulty than non-infected children in the second year of life. The matched subjects design adopted gives some strength to the conclusion that HIV-1 infection impairs the genesis rather than the later development of language in infected but not ill children.

Objective The aims of the study were: (a) to propose focal refinements to the cold pressor test (CPT) for the pediatric population, contributing to the development of subjective and behavioral norms; (b) to analyze the influence of personal (gender, age, and skin-fold thickness), and psychological (anxiety, depression, internalization, and externalization) variables on pain perception and its correlation with room temperature. Methods After a phase of adaptation in a water bath (24–27 � C), the child immersed one arm in cold water (10 � C) and reported pain threshold and tolerance. Results The test was conducted on 141 healthy children. Pain tolerance was reached within the first minute by 50% of the children. Pain intensity affected the children’s emotional status. Older children tolerated pain for longer. Gender, psychological, and environmental variables did not influence pain perception. Conclusion This study provides methodological refinements to the CPT contributing to the development of norms for children.

Summary Background: There is limited evidence on the analgesic efficacy of opioids during percutaneous intravenous central catheter (PICC) insertion in preterm infants. Aim: To assess the analgesic and procedural efficacy of low-dose remifentanil infusion during PICC in preterm infants. Methods: Fifty-four neonates [mean gestational age (±sd) 28 ± 2 weeks; birth weight 1126 ± 337 g] were randomly assigned to remifentanil infusion at 0.03 mcg·kg−1·min−1 (R) or placebo (C) in addition to 0.3 ml of 12% sucrose per os and non-nutritive sucking. Results: Validated pain scales [Neonatal Infants Pain Scale (NIPS) and Premature Infants Pain Profile (PIPP)] administered at the baseline T0, skin preparation T1, needle insertion T2, and recovery T3, revealed differences in mean NIPS scores (C 5.3 ± 1.3 vs R 4.2 ± 1.4 at T1 and C 5.0 ± 1.3 vs R 3.4 ± 1.3 at T2) and PIPP scores (C 9.3 ± 1.6 vs R 7.1 ± 1.5 at T1 and C 8.6 ± 1.7 vs R 6.1 ± 1.4 at T2); P

Mucopolysaccharidosis type II (MPSII) is an inherited disorder due to a deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS). The disease is characterized by a considerable deposition of heparan- and dermatan-sulfate, causing a general impairment of physiological functions. Most of the therapeutic protocols proposed so far are mainly based upon enzyme replacement therapy which is very expensive. There is a requirement for an alternative approach, and to this aim, we evaluated the feasibility of muscle electro gene transfer (EGT) performed in the IDS-knockout (IDS-ko) mouse model. EGT is a highly efficient method of delivering exogenous molecules into different tissues. More recently, pre-treatment with bovine hyaluronidase has shown to further improve transfection efficiency of muscle EGT. We here show that, by applying such procedure, IDS was very efficiently produced inside the muscle. However, no induced IDS activity was measured in the IDS-ko mice plasma, in contrast to matched healthy controls. In the same samples, an anticipated and rapidly increasing immune response against the recombinant protein was observed in the IDS-ko vs control mice, although reaching the same levels at 5 weeks post-injection. Additional experiments performed on healthy mice showed a significant contribution of hyaluronidase pre-treatment in increasing the immune response.

Objective. The aim of this study was to investigate the validity of office spirometry in primary care pediatric practices. Methods. Ten primary care pediatricians undertook a spirometry training program that was led by 2 pediatric pulmonologists from the Pediatric Department of the University of Padova. After the pediatricians' training, children with asthma or persistent cough underwent a spirometric test in the pediatrician's office and at a pulmonary function (PF) laboratory, in the same day in random order. Both spirometric tests were performed with a portable turbine flow sensor spirometer. We assessed the quality of the spirometric tests and compared a range of PF parameters obtained in the pediatricians' offices and in the PF laboratory according to the Bland and Altman method. Results. A total of 109 children (mean age: 10.4 years; range: 6–15) were included in the study. Eighty-five (78%) of the spirometric tests that were performed in the pediatricians' offices met all of the acceptability and reproducibility criteria. The 24 unacceptable test results were attributable largely to a slow start and failure to satisfy end-of-test criteria. Only the 85 acceptable spirometric tests were considered for analysis. The agreement between the spirometric tests that were performed in the pediatrician's office and in the PF laboratory was good for the key parameters (forced vital capacity, forced expiratory volume in 1 second, and forced expiratory flow between 25% and 75%). The repeatability coefficient was 0.26 L for forced expiratory volume in 1 second (83 of 85 values fall within this range), 0.30 L for forced vital capacity (81 values fall within this range), and 0.58 L/s for forced expiratory flow between 25% and 75% (82 values fall within this range). In 79% of cases, the primary care pediatricians interpreted the spirometric tests correctly. Conclusions. It seems justifiable to perform spirometry in pediatric primary care, but an integrated approach involving both the primary care pediatrician and certified pediatric respiratory medicine centers is recommended because effective training and quality assurance are vital prerequisites for successful spirometry.

Following cystic fibrosis (CF) neonatal screening implementation, a high frequency of heterozygotes has been reported among neonates with elevated immunoreactive trypsinogen (IRT) and normal sweat chloride levels. We studied the relationship between normal IRT values and CF heterozygosity: 10,000 neonates were screened for CF by IRT measurement and tested for 40 CF mutations; the 294 carriers detected were coupled with newborns negative to the same genetic testing, and the two groups' IRT levels compared. Heterozygotes had higher IRT levels than their controls (mean 35.32 vs. 27.58 μg/L, P

Summary Background: The efficacy of the Neonatal Resuscitation Program (NRP) courses was previously evaluated, demonstrating good retention of knowledge in the participants. However, there is a lack of information regarding the participants’ performance in relation to the different steps of neonatal resuscitation. We aimed to assess the knowledge gained and retained by pediatric residents who participated in a NRP course in relation to the different steps. Methods: An 80-item questionnaire derived from the standard test contained in the American Heart Association and American Academy of Pediatrics Neonatal Resuscitation Manual was given to 25 pediatric residents before, immediately after and 6 months after the course. Results: The percentages of correct answers significantly improved from before (37.6 ± 3.1%) to immediately after the course (94.1 ± 0.9%) (P

Human infertility in relation to mutations affecting the cystic fibrosis transmembrane regulator (CFTR) gene has been investigated by different authors. The role of additional variants, such as the possible forms of the thymidine allele (5T, 7T and 9T) of the acceptor splice site of intron 8, has in some instances been considered. However, a large-scale analysis of the CFTR gene and number of thymidine residues, alone and in combination, in the two sexes had not yet been addressed. This was the aim of this study. Two groups were compared, a control group of 20,532 subjects being screened for perspective reproduction, and the patient group represented by 1854 idiopathically infertile cases. Analyses involved PCR-based CFTR mutations assessment, reverse dot-blot IVS8-T polymorphism analyses, denaturing gradient gel electrophoresis (DGGE) and DNA sequencing. The expected 5T increase in infertile men was predominantly owing to the 5/9 genotypic class. The intrinsic rate of 5T fluctuated only slightly among groups, but some gender-related differences arose when comparing their association. Infertile men showed a significantly enriched 5T + CFTR mutation co-presence, distributed in the 5/9 and 5/7 classes. In contrast, females, from both the control and the infertile groups, showed a trend towards a pronounced reduction of such association. The statistical significance of the difference between expected and observed double occurrence of 5T + CFTR traits in women suggests, in line with other reports in the literature, a possible survival-hampering effect. Moreover, regardless of the 5T status, CFTR mutations appear not to be involved in female infertility. These results underline the importance of (i) assessing large sample populations and (ii) considering separately the two genders, whose genotypically opposite correlations with these phenomena may otherwise tend to mask each other.

This report presents the long-term (36 months) neurologic outcome in 12 neonates and 9 children who survived after extracorporeal membrane oxygenation and attempts to identify its prognostic indicators through a prospective study in the pediatric intensive care unit of a university hospital. Outcome assessment, neurodevelopmental tests, electroencephalogram, auditory evoked potentials, visual evoked potentials, and somatosensory evoked potentials, cerebral sonography, or cerebral tomography were evaluated at the end of bypass and at 6, 12, 24, and 36 months after extracorporeal membrane oxygenation. "Before extracorporeal membrane oxygenation" variables (oxygenation index, pH, oxygen arterial partial pressure) and "during extracorporeal membrane oxygenation" variables (pH, oxygen arterial partial pressure, duration of bypass, clotting activated time, electroencephalogram) were also analyzed. A negative neurologic outcome (Glasgow Outcome Score different from "good recovery" or neurodevelopmental score less than 70) 12 months after extracorporeal membrane oxygenation was documented in 8.3% of neonates and in 30% of children who survived. There was no further change in subsequent evaluations (24 and 36 months follow-up). The most abnormal electroencephalogram during extracorporeal membrane oxygenation, the first electroencephalogram, neuroimaging score, and somatosensory evoked potentials after extracorporeal membrane oxygenation treatment were associated with negative neurologic outcome. The study documented that neonates and children treated with extracorporeal membrane oxygenation require long-term follow-up; electroencephalogram, neuroimaging score, and somatosensory evoked potentials have prognostic value for abnormal neurologic outcome.

Objectives Little attention has been paid to the assessment of pain in children with developmental delay. The aim of this study was to explore several methods for assessing pain during venipuncture in this population of children, using classic and modified scales to evaluate the children's response to simplified tools. Methods Sixteen children with mild or moderate developmental delay were evaluated using three standard self-rating scales (Visual Analog Scale [VAS], Eland Scale, and Faces Scale) and three modified methods (Cube Test, Modified Eland Scale, and Modified Faces Scale), recording subjective self-ratings and behavioral expressions of pain during a venipuncture procedure, apart from the initial fear. The children's pain and reaction time were assessed by an outside observer, while their pain and fear were also evaluated by the parents. Results The VAS was used without difficulty by all the children and revealed a good consistency with the Cube Test. The parents' and neutral observer's indirect pain assessment was also consistent with the child's evaluations. The Eland Scale proved difficult to use, especially for Down's syndrome children, while its modified version was easier. Results emerging from the original and modified Faces Scales were inconsistent. Frightened children attributed higher pain scores, demonstrating that negative emotions exacerbate the experience of pain in developmentally delayed children. The patients showed a limited capacity for verbal and behavioral expression in reaction to the painful stimulus (especially the Down's cases). Discussion These findings support the conviction that even developmentally delayed children can use self-rating methods effectively. This sector demands further, more extensive study, including the development of simplified tools, to ensure an adequate pain assessment and optimal antalgic approach to this particular pediatric population.

Cysteinyl-leukotrienes (cys-LTs) and 8-isoprostane are biomarkers of airway inflammation and oxidative stress.The aim of this study was to evaluate cys-LT and 8-isoprostane levels in exhaled breath condensate (EBC) of children with different degrees of asthma severity.EBC was collected from 14 steroid-naive children with mild persistent asthma, 13 children with stable mild- to-moderate persistent asthma treated with inhaled corticosteroids (ICS), 9 ICS-treated children with unstable asthma, and 19 healthy children.In the three groups of asthmatic children, EBC concentrations of cys-LTs and 8-isoprostane were significantly higher than in control children (steroid-naive asthmatic children: cys-LTs median, 10.8 pg/mL, P.001, 8-isoprostane, 16.2 pg/mL, P.001; ICS-treated stable asthmatic children: cys-LTs, 12.7 pg/mL, P.001, 8-isoprostane, 18.1 pg/mL, P.001; children with unstable asthma: cys-LTs, 106.0 pg/mL, P.01, 8-isoprostane, 29.7 pg/mL, P.01; control children: cys-LTs, 4.3 pg/mL, 8-isoprostane, 3.5 pg/mL). Cys-LT levels were higher in children with unstable asthma than in the other two asthmatic groups (P.05). FE(NO) levels were significantly higher in steroid-naive and in children with unstable asthma compared with ICS-treated children with stable asthma (P.01).Our study shows that EBC cys-LTs and 8-isoprostane concentrations are higher in asthmatic children than in healthy control children, with scattered values in patients with unstable asthma. These findings suggest that EBC eicosanoid measurement may have useful clinical implications for investigating phenotype differences among asthmatic patients.

Ten children (4.6%) among a cohort of 219 with Kawasaki disease (KD) had their onset with severe abdominal complaints. Incomplete KD presentation at the time of acute abdomen was present in nine of 10 patients. Acute abdominal pain and distension, vomiting, hepatomegaly, and jaundice were the most common symptoms at onset. Hematemesis was present in one; toxic shock syndrome requiring care in the intensive care unit occurred in four. Five patients had laparotomy, three had percutaneous transhepatic biliary drainage, and one had a gastrointestinal endoscopy. Postoperative diagnosis was gallbladder hydrops with cholestasis in five, paralytic ileus in three, appendicular vasculitis in one, and hemorrhagic duodenitis in one. All patients completely recovered, but 50% developed coronary aneurysms despite early intravenous gammaglobulin treatment. Acute surgical abdomen can be the presenting manifestation of KD. In older children with fever, rash, and acute abdominal pain or hematemesis, KD should be considered in the differential diagnosis. J Pediatr 2003;142:731-5)