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Objective This study aimed to determine whether neonatal hyperbilirubinemia is associated with a risk of autism spectrum disorder (ASD) using a large population-based cohort.Study Design This retrospective cohort study used data from the children's database (2000–2012) of the National Health Insurance Research Database (1996–2012) in Taiwan. We included neonates who were born between 2000 and 2004 and aged Results A total of 67,017 neonates were included. The neonates with hyperbilirubinemia were associated with 1.28-fold increased risk of ASD (HR = 1.28, 95% confidence interval [CI]: 1.05–1.57) compared with those without hyperbilirubinemia. In subanalysis to determine how phototherapy and exchange transfusion treatment for hyperbilirubinemia were associated with ASD showed no association between treatment and ASD, suggesting the lack of a dose-response effect of hyperbilirubinemia on the risk of ASD. Boys had a nearly six-fold higher risk of ASD than girls (HR = 5.89, 95% CI: 4.41–7.86). Additionally, neonates born with preterm birth and low birth weight were associated with a risk of ASD (HR = 1.46, 95% CI: 1.00–2.13).Conclusion We did not observe a dose-response effect of hyperbilirubinemia on ASD, but neonatal hyperbilirubinemia may be an independent risk factor for ASD if there is a residual confounding by other perinatal complications. Therefore, this study does not support a causal link between neonatal hyperbilirubinemia exposure and the risk of ASD.

Tuberous sclerosis complex (TSC) is a rare disease that causes multisystem benign neoplasm, induced by dysregulation of the mammalian target of the rapamycin pathway (mTOR). This study aimed to examine the effects of continuous low-dose everolimus, a potent and selective inhibitor of mTOR, on the treatment of TSC-associated renal angiomyolipoma (AML). Between July 2013 and August 2017, 11 patients with TSC-AML were enrolled for an everolimus therapy protocol. An oral everolimus dose starting at 2.5 mg daily was gradually increased to 5.0 mg daily. All patients were evaluated using MRI or CT scanning at baseline, 12, 24, 36 and 48 months after the start of treatment for measuring changes of renal AML mass volume. Everolimus therapy resulted in significant shrinkage of TSC-AML volume after 48 months follow-up. Serum levels of everolimus were subdivided into group I (8 ng/mL, n=5). The volume reduction rates were 10.6%–65.2% in group I and 42.5%–70.6% in group II. To evaluate the response to treatment, three of six (50%) were responders in group I, and all the patients in group II (5/5, 100%) were responders. The differences in AML volume reduction between the groups were statistically significant at 12 months (p=0.011), 24 months (p=0006), 36 months (p=0.014) and 48 months (p=0.05). These results suggest that continuous low-dose everolimus therapy (2.5–5 mg daily) might be effective in shrinking TSC-AML volume and minimizes adverse effects and subsequent reducing medical costs.

Objective: The main objective of this study was to evaluate the efficacy and safety of Lactobacillus rhamnosus in children aged 4–48 months with atopic dermatitis. Methods: The design of this study was a two-center, double-blind, randomized, and placebo-controlled study with two parallel groups to evaluate the efficacy and safety profile of L. rhamnosus in children aged 4–48 months with atopic dermatitis diagnosed using Hanifin and Rajka criteria and with a Scoring of Atopic Dermatitis (SCORAD) ≥ 15 at enrollment. The duration of this study was 8 weeks with a total of five visits. The enrolled patients were allocated into either a treatment group (one ComProbi capsule containing L. rhamnosus a day) or a control group (one capsule of placebo a day) at a ratio of 1:1. The primary endpoint was to compare the mean change from baseline in SCORAD after 8 weeks of treatment. The other secondary end points were to compare the following: the mean changes from baseline in SCORAD at postbaseline visits, the frequency and total amount of the use of corticosteroids during the 8-week treatment, the frequency of atopic dermatitis and the symptom-free duration, the mean changes from baseline in Infant Dermatitis Quality of Life Questionnaire at Week 4 and Week 8, and the mean changes from baseline in the Dermatitis Family Impact Questionnaire at Week 4 and Week 8. Results: The mean changes in SCORAD from baseline at Week 8 was −21.69 ± 16.56 in the L. rhamnosus group and −12.35 ± 12.82 in the placebo group for the intent-to-treat population (p = 0.014). For the per-protocol population, the mean change of SCORAD from baseline was −23.20 ± 15.24 in the L. rhamnosus group and −12.35 ± 12.82 in the placebo group (p = 0.003). Significant differences were demonstrated between groups at Week 8 in intensity in the intent-to-treat population and per-protocol population. Throughout the period, the amount of topical corticosteroids used showed no difference between groups. No significant difference was noted in the overall symptom-free durations compared with the placebo group. Infant Dermatitis Quality of Life Questionnaires and Dermatitis Family Impact Questionnaires scores improved significantly at Week 4 and Week 8 but did not reach statistical significance. Adverse events were documented in 14/33 patients in the L. rhamnosus group (42.42%, 35 events) and in 15/33 placebo patients (45.45%, 37 events). Conclusions: The results of this study indicated that L. rhamnosus was effective in decreasing symptoms of atopic dermatitis after an 8-week treatment by comparing the mean change of SCORAD from baseline with a placebo (p

Attention-deficit/hyperactivity disorder (ADHD) and nocturnal enuresis are common disorders with extensive psychosocial suffering in affected children, and healthcare burden on parents. Whether the childhood psychological disorders and nocturnal enuresis are factors contributing to ADHD have not been clearly established. This study conducted a population-based case–control study using data sets from the National Health Research Insurance database, and identified 14 900 children diagnosed with ADHD. Risk factors that have been associated with or possibly related to ADHD development were included in this study. Performance of in groups of ADHD with enuresis was compared with controls. With adjustment for potential covariates, participants with enuresis exhibited a 2.24-fold greater risk of subsequent ADHD development compared with controls (95% CI 1.84 to 2.73). Participants with enuresis and comorbidity had a significantly greater risk of ADHD than those with no enuresis and no comorbidity (adjusted OR=8.43, 95% CI 4.38 to 16.2). Children who are assessed for ADHD should be evaluated for the presence of enuresis or other neurobehavioral comorbidities. Multidisciplinary treatment may benefit children with ADHD and minimize psychological burden on parents.

We appreciate the comments by Jogender and Jaivinder regarding our article on the association between neonatal hyperbilirubinaemia and type 1 diabetes (T1D) [1]. They highlight bilirubin as an anti...

Little is known about whether allergic disease is associated with a subsequent increased risk of childhood-onset epilepsy. We used a large, population-based cohort study to examine whether children with antecedent allergic rhinitis (AR) were associated with a subsequent increased risk of epilepsy.This retrospective population-based cohort study was conducted by using data from the 2000-2012 Taiwan's National Health Insurance Research Database. We enrolled 67,537 children aged 0-18 years diagnosed with AR and 67,537 age- and gender-matched children without the diagnosis of AR. The incidence rate (per 10,000 person-years) of epilepsy was calculated. We used Cox proportional hazards regression analysis to estimate hazard ratios (HRs) and 95 % confident interval (CI).Of the 135,074 children included in the analyses, those with AR had a higher incidence rate of epilepsy (6.84 versus 3.95 per 10,000 person-years, p0.001) and an earlier age at diagnosis of epilepsy than those without AR [8.54 (4.90) versus 9.33 (5.40) years, p = 0.03)]. The Kaplan-Meier survival analysis demonstrated that the children with AR had a higher likelihood of developing epilepsy than those without AR (p 0.001). After adjusting for confounding factors in multivariate model, children with AR had a 76 % increased risk of epilepsy (HR 1.76, 95 % CI 1.51-2.04) than those without AR. Boys had a 21 % increased risk of epilepsy (HR 1.21, 95 % CI 1.05-1.40) than girls.These results suggest that children with AR were associated with an increased subsequent risk of epilepsy.

Background: Type 1 diabetes (T1D) is one of the most common chronic diseases of childhood. Whether neonatal hyperbilirubinaemia increases the risk of T1D remains unclear.Aim: To estimate the associ...

Streptococcus pneumoniae is a common cause of infectious diseases in children that may lead to life-threatening complications. Acute purulent pericarditis is an uncommon complication of S. pneumoniae in the antibiotic era. A healthy 4-year-old girl was admitted with pneumonia and pleural effusion. She had received one catch-up dose of 13-valent pneumococcal conjugate vaccine at 2 years of age. She rapidly developed necrotizing pneumonia, complicated by bronchopleural fistula presenting as subcutaneous emphysema and pneumothorax and acute purulent pericarditis. S. pneumoniae serotype 19A was subsequently identified from blood, empyema and pericardial fluid cultures. After appropriate antibiotic therapy and a right lower lobectomy, her condition stabilized and she promptly recovered. This case highlights two rare potential clinical complications of pneumococcal disease in a child: necrotizing pneumonia and acute purulent pericarditis. This is the first report of a child who received just one catch-up dose of 13-valent pneumococcal conjugate vaccine at 2 years of age, as per the United States' Advisory Committee on Immunization Practice's recommendations, but who still developed severe invasive pneumococcal disease with life-threatening complications caused by S. pneumoniae serotype 19A.

Background This study was designed to examine the capability of renal ultrasonography (US) for predicting vesicoureteral reflux (VUR) and renal scarring (RS), and to assess, using initial US, the significant urologic abnormalities that impact on management of children hospitalized with a first febrile urinary tract infection (UTI). Methods Hospitalized children aged ≤ 2 years with a first febrile UTI were prospectively evaluated using imaging studies, including (99m)Tc dimercaptosuccinic acid (DMSA) scan, US, and voiding cystourethrography. Results Of the 310 children analyzed (195 boys and 115 girls), 105 (33.9%) had abnormal US. Acute DMSA scans were abnormal in 194 children (62.6%), including 89 (45.9%) with concomitant abnormal US. There was VUR in 107 children (34.5%), including 79 (25.5%) with Grades III-V VUR. The sensitivity and negative predictive values of US were 52.3% and 75.1%, respectively, for Grades I-V VUR and 68.4% and 87.8%, respectively, for Grades III-V VUR. Eighty-five children (27.4%) had RS, including 55 (64.7%) with abnormal US. Of the 105 children with abnormal US, 33 (31.4%) needed subsequent management (surgical intervention, parental counseling, or follow up of renal function). Nephromegaly on initial US and Grades III-V VUR were risk factors of RS. Conclusion Abnormal US may carry a higher probability of Grades III-V VUR and RS, and can affect subsequent management in a significant number of children. Nephromegaly on initial US and Grades III-V VUR are strongly associated with an increased risk for RS. Thus, US should be performed on children after a first febrile UTI and children with normal US may not require voiding cystourethrography.

Steroid-insensitive asthma-related airway inflammation is associated with the expression of epidermal growth factor receptor (EGFR) tyrosine kinase in asthmatic bronchial epithelium. Proinflammatory cytokines IL-6 and IL-8 are related to steroid-insensitive asthma. It is currently unknown how EGFR-tyrosine kinase inhibitors (EGFR-TKIs) affects house dust mite (HDM)-induced asthma in terms of inflammatory cytokines related to steroid-resistant asthma and further signaling pathway. Cytokine expressions and EGFR signaling pathway were performed by ELISA, reverse transcriptase PCR, real-time PCR, and Western blot in cell-line models. AMP-activated protein kinase (AMPK) pathway-related inhibitors were applied to confirm the association between EGFR-TKI and AMPK pathway. HDM induced IL-6 and IL-8 in a dose-dependent manner. Both Erlotinib (Tarceva) and Osimertinib (AZD-9291) reduced the levels of HDM-stimulated IL-6 and IL-8 levels in BEAS-2B cells. AZD-9291 was more effective than Erlotinib in inhibiting phospho-EGFR, and downstream phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and phopho-signal transducer and activator of transcription 3 (p-STAT3) pathway signaling. In addition, AMPK pathway-related inhibitor, Calcium-/calmodulin-dependent protein kinase kinase β (CaMKKβ) inhibitor, down-regulated IL-8, but EGFR-TKI had no effect on AMPK pathway. Our findings highlight EGFR-TKIs, Tarceva, and AZD-9291, attenuate HDM-induced inflammatory IL-6 and IL-8 cytokines via EGFR signaling axis pathway, but not AMPK signaling pathway.

Background: The clinical manifestations of Leigh Syndrome (LS) are heterogeneous and its diagnosis is often based on information acquired from multiple levels of inquiry. To identify LS, Oral Glucose Lactate Stimulation Test (OGLST) and Magnetic Resonance Spectroscopy (MRS) have been used as additional tools for evaluation of this metabolic disorder. The objective of the study was to report the clinical manifestations, neuroimaging assessments, and multidisciplinary approaches of lactate in pediatric patients with LS. Methods: We performed a retrospective charts review of pediatric patients with LS, which underwent the investigations using laboratory tests and Magnetic Resonance Images (MRI)/MRS of the brain. Results: The distributions of the lesions on the MRI of the brain studies were as the following: basal ganglia (7/8), brainstem (7/8), and cortex (3/8). Despite all of the patients showed disorient neurological manifestations and symmetrical lesions over the basal ganglion and brainstem on MRI, elevated levels of serum lactate were detected in 6 of 8 patients by either random serum sample obtained for lactate or OGLST. Subsequently, the remaining 2 cases were demonstrated with lactate peak over the affected areas by MRS. Cranial MRS showed lactate duplex and decreased N-acetylaspartate/creatine ratio over the affected areas in the 5 of 6 patients. Conclusions: The study shows the importance of multidisciplinary approaches in the diagnosis of LS. Approach of LS may not only depend on the elevation of the value of random serum lactate but also can be further aided by OGLST or MRS to evaluate metabolic disorder in such patients.

Little is known about the associations between allergic disease, sleep-disordered breathing (SDB), and childhood nocturnal enuresis (NE). We examined whether allergic disease and SDB were associated with childhood NE. Data were assessed from the 2007–2012 Taiwan National Health Insurance Research Database. We enrolled 4308 children aged 5–18 years having NE diagnosis and age- and sex-matched 4308 children as the control group. The odds ratios of NE were calculated to determine an association with preexisting allergic disease and SDB. A total of 8616 children were included in the analysis. Prevalence of allergic diseases and SDB was significantly higher for the NE group than the control group (all p

We report 2 cases of neonatal Legionella infection associated with aspiration of contaminated water used in hospitals to make infant formula. The molecular profiles of Legionella strains isolated from samples from the infants and from water dispensers were indistinguishable. Our report highlights the need to consider nosocomial legionellosis among neonates who have respiratory symptoms.

Deficiency of hypoxanthine phosphoribosyltransferase activity is a rare inborn error of purine metabolism with subsequent uric acid overproduction and neurologic presentations. The diagnosis of Lesch–Nyhan syndrome (LNS) is frequently delayed until self-mutilation becomes evident. We report the case of a boy aged 1 year and 10 months who was diagnosed with profound global developmental delay, persistent chorea, and compulsive self-mutilation since the age of 1 year. Serial serum uric acid levels showed normal uric acid level, and the spot urine uric acid/creatinine ratio was >2. The hypoxanthine phosphoribosyltransferase cDNA showed the deletion of exon 6, and the boy was subsequently diagnosed to have LNS. He also had respiratory distress due to pulmonary embolism documented by chest computed tomography scan. This report highlights the need to determine the uric acid/creatinine ratio caused by increased renal clearance in LNS in young children. The presence of pulmonary embolism is unusual and may be the consequence of prolonged immobilization.

BackgroundRotavirus and norovirus are the most common known causes of viral gastroenteritis in children. This study examined the association between serum interleukin 6 (IL-6) and interleukin 8 (IL-8) levels and disease severity in the acute phase of rotavirus and norovirus gastroenteritis in children, and it also explored the role of fecal cytokine levels in children with viral and bacterial gastroenteritis.MethodsThis prospective study enrolled patients aged 4 months to 14 years admitted with acute gastroenteritis in a tertiary care center. Peripheral blood samples were collected for IL-6 and IL-8 assays within the first 3 days of diarrhea. Stool samples were obtained from the patients in the first 24 hours after admission.ResultsSerum IL-6 and IL-8 were measured in children with viral (n = 66) and bacterial (n = 23) infections, and in healthy controls (n = 10). In the acute phase of gastroenteritis, a moderately positive correlation was found between serum IL-6 levels and disease severity (rs = 0.41, p

Renal manifestations of tuberous sclerosis complex (TSC) occur with a high frequency and a wide range of severity. The onset and complications of each affected organ depend on the age. This study aimed to investigate the associations between comorbidities, frequency, and size of cysts/angiomyolipomas of TSC and the patients in the different ages.We performed a systematic evaluation of patients with TSC at integrated clinics for TSC. The patients were diagnosed with TSC according to Roach's clinical diagnostic criteria. All the patients underwent a systematic evaluation with a medical history review, recording of cutaneous manifestations, magnetic resonance imaging of the brain, chest computed tomography scan, and cardiac echography. Each patient was routinely evaluated with renal magnetic resonance imaging.Of the 57 patients with TSC, renal lesions or manifestations were observed in 38.5 % at preschool-age group (6 years) that increased to 75.0, 85.7, and 100 % in school-age group (6-18 years), young adulthood group (18-30 years), and middle-aged group30 years, respectively. Renal complications or interventions were found in 72.7 % of patients30 years. There was a strongly positive association between the size of renal lesions and age (p0.001). Comorbidities of TSC were significantly correlated with pulmonary lymphangiomyomatosis (p0.001) and seizure remission (p = 0.018).The results indicate a positive association of progressively growing renal lesions in patients with TSC with increasing age. It is mandatory for clinicians that monitor the high-risk patients to minimize and prevent renal complications in the future.

Since 1998 in Taiwan, enterovirus (EV) 71 epidemics have caused encephalomyelitis and placed a significant burden on parents and physicians. In this study, we present clinical manifestations, magnetic resonance (MR) imaging findings, and neurological sequelae on epidemic EV-infected patients with encephalomyelitis. Of the 46 patients, 14 patients presented with neurological sequelae; of them, 3 patients suffered from complications of mental regression. Predictors of unfavorable neurological sequelae were myoclonic jerks (> 4 times/night) and pleocytosis (167/μL) of the cerebrospinal fluid (CSF). Results from viral culture and MR imaging indicated that positive identification of EV71 infection was associated significantly with lesions on MR imaging. Our results show that hand-foot-mouth disease carries a higher risk of encephalomyelitis and that frequent myoclonic jerks and pleocytosis of the CSF are risk factors for subsequent neurological sequelae. Positive identification of EV71 might be useful as a predictor of lesions in MR imaging.

This study aimed to examine the ability of acute (99m)Tc DMSA scan for predicting dilating (grades III-V) vesicoureteral reflux (VUR) after a first febrile urinary tract infection in children aged 2 years or younger.All children underwent ultrasonography (US), (99m)Tc DMSA scan, and voiding cystourethrography. Sensitivity, specificity, positive and negative predictive values, likelihood ratios, and receiver operating characteristic curves were performed to assess the diagnostic accuracy for predicting dilating VUR. Follow-up scan was performed at least 6 months after the acute infection to evaluate the presence of renal scarring (RS) or new scars.Of the 473 children analyzed (289 boys and 184 girls; median age, 5 months), 282 (59.6%) had abnormal acute (99m)Tc DMSA scan findings. There was VUR in 153 children (32.3%), whereas 95 (20.1%) had dilating VUR. The sensitivity and negative predictive value in predicting dilating VUR were 95.8% and 97.9%, respectively, for (99m)Tc DMSA and 97.9% and 98.6%, respectively, for combined US and (99m)Tc DMSA, whereas the positive and negative likelihood ratios were 1.90 and 0.08, respectively, for (99m)Tc DMSA and 1.57 and 0.06, respectively, for combined studies. On multivariate analysis, dilating VUR was a predictor for developing RS and new scars.Our results reveal the usefulness of acute (99m)Tc DMSA scan for predicting dilating VUR in children with a first febrile urinary tract infection. A voiding cystourethrography is indicated in only children with abnormalities found on a (99m)Tc DMSA and/or a US. The presence of dilating VUR predisposes to developing RS and new scars.

Background Data on urinary tract infection (UTI) in infants ≤2 months of age are limited. We examined clinical characteristics, antimicrobial resistance, imaging findings and clinical outcomes in infants ≤2 months of age and children 2-24 months of age hospitalized with the first febrile UTI. Methods Children ≤24 months of age hospitalized with their first-diagnosed febrile UTI were prospectively studied. Renal ultrasonography, Tc-dimercaptosuccinic acid scanning and voiding cystourethrography were performed in all children. Results Of the 388 children analyzed (255 boys and 133 girls), 61 patients were ≤2 months of age, representing 15.7% of the whole population, whereas 327 patients were 2-24 months of age. Escherichia coli was the predominant bacterium, with similar antimicrobial resistance in the 2 groups, and associated E. coli bacteremia occurred in 9 patients (2.3%). Renal ultrasonography showed abnormal findings in 130 patients (33.5%), but there was no difference in the rate of abnormal findings between the groups. Vesicoureteral reflux (VUR) was present in 130 children (33.5%), including 93 (24%) with grades III-V VUR. VUR was more prevalent in the infants ≤2 months of age (P = 0.007), but there was no difference in the prevalence of grades III-V VUR between the groups. The incidence of renal scarring was 28.6% (111/388), and it did not differ between the groups. Conclusions There are similarities in clinical characteristics, antimicrobial resistance, imaging findings and clinical outcomes after a first UTI between the young infants ≤2 months and children 2-24 months of age. The same guidelines for the diagnosis and management after the first febrile UTI can be applied to children who are ≤24 months of age.

Background: The association between neonatal jaundice and childhood asthma is a new finding of two reports. The purpose of the study was to verify their results. Methods: Data from 11,321 children were collected from the National Health Insurance Research Database. Their claims data were evaluated from birth to 10 yr old. Children were analyzed as case (those with neonatal jaundice) and controls (those without neonatal jaundice). The diagnostic criteria for asthma were as follows: at least four asthma diagnoses at outpatient services and emergency department (ED), or one asthma diagnosis during an admission. In children fitting the asthma criteria, those with no asthma diagnosis after 1 yr of age were excluded. Mantel–Haenszel’s odds ratios were calculated after adjustment for the following confounders: preterm/low birth weight, neonatal infection, other respiratory conditions, other birth conditions, and gender. Asthma rate, onset time, the use of drugs, upper respiratory infection and lower respiratory infection (LRI) rates, hospital admission/ED visit rates, and the effect of phototherapy were evaluated. Results: After adjustment for the confounding factors, the rate of asthma was higher in icteric children (OR: 1.64, 95% CI 1.36–1.98, p

Objectives Urinary tract infection (UTI) is a common bacterial infection in children that can result in permanent renal damage. This study prospectively assessed the diagnostic performance of procalcitonin (PCT) for predicting acute pyelonephritis (APN) among children with febrile UTI presenting to the paediatric emergency department (ED). Methods Children aged ≤10 years with febrile UTI admitted to hospital from the paediatric ED were prospectively studied. Blood PCT, C reactive protein (CRP) and white blood cell (WBC) count were measured in the ED. Sensitivity, specificity, predictive values, multilevel likelihood ratios, receiver operating characteristic (ROC) curve analysis and multivariate logistic regression were used to assess quantitative variables for diagnosing APN. Results The 136 enrolled patients (56 boys and 80 girls; age range 1 month to 10 years) were divided into APN (n=87) and lower UTI (n=49) groups according to 99mTc-dimercaptosuccinic acid scan results. The cut-off value for maximum diagnostic performance of PCT was 1.3 ng/ml (sensitivity 86.2%, specificity 89.8%). By multivariate regression analysis, only PCT and CRP were retained as significant predictors of APN. Comparing ROC curves, PCT had a significantly greater area under the curve than CRP, WBC count and fever for differentiating between APN and lower UTI. Conclusions PCT has better sensitivity and specificity than CRP and WBC count for distinguishing between APN and lower UTI. PCT is a valuable marker for predicting APN in children with febrile UTI. It may be considered in the initial investigation and therapeutic strategies for children presenting to the ED.

Complete agenesis of the bladder and urethra is an extremely rare congenital anomaly and most of these patients are stillborn or die during infancy. We report the case of a 1-month-old female infant with bladder and urethral agenesis who presented with bilateral dilated and tortuous ectopic ureters draining into the vagina diagnosed using MR imaging. Our patient was maintained on antibiotic prophylaxis and she remained well during the 3-year follow-up. MR imaging can be used as a valuable modality for genitourinary abnormalities, particularly in cases of inconclusive ultrasound or retrograde pyelography findings.

Leflunomide, an immunosuppressant with antiviral activity, was used to treat 5 children with severe BK virus-associated hemorrhagic cystitis after hematopoietic stem cell transplantation. Without severe side effects, BK viral loads in blood and urine decreased significantly after leflunomide treatment. Compared with 7 historical controls, duration of BK virus-associated hemorrhagic cystitis was significantly shorter in patients receiving leflunomide therapy (P < 0.01).

Background There is growing evidence of positive correlations between asthma (AS) and obesity in adults and children. Leptin is an obesity gene product secreted by white adipose tissue; elevated serum levels are found in obese adults and children. Recently, leptin has also been found to be associated with allergic rhinitis (AR). However, the links between serum leptin, atopic AS, and AR remained undetermined. Because AS and AR share common allergic inflammatory mechanisms, our aim was to determine if there were any differences in serum leptin levels between asthmatic children and nonasthmatic children with AR. Methods We studied 114 children (67 boys and 47 girls): 68 with mild intermittent-to-moderate persistent atopic AS (AS children) and 46 with mild-to-moderate persistent AR without AS (AR children; overall mean age, 8.51 years; range, 5–18 years). Body mass index (BMI), serum leptin, pulmonary function, and atopy parameters (serum IgE and eosinophil levels) were measured. Results Compared with AR children, AS children had higher body weights (kg), body mass indices (kg/cm2), and serum leptin levels (ng/mL). Multiple linear regression analyses showed that serum leptin concentrations differed significantly for girls, being overweight and between disease groups (AS and AR children). Conclusion Our results indicate that a higher serum leptin level has stronger association with mild-to-moderate persistent AS compared with AR. Hence, serum leptin may be a stronger predictor for childhood AS compared with AR. Among the asthmatic children, higher serum leptin levels also showed stronger associations with female gender and being overweight.

Spinal abscess is rare in children, especially in young infants. The most common etiology is bacteria, Staphylococcus aureus in particular. Mycobacterium tuberculosis is another cause. We report an unusual cervical spinal abscess with spinal cord compression in a 13-month-old child. The presenting symptoms were weakness in the right arm and, predominantly, the right leg for 1 month. Magnetic resonance imaging showed an abscess of the cervical spine, extension with bony destruction, and spinal cord compression. The patient underwent an emergency neurosurgical decompression and laminectomy. Pathology and culture results confirmed Mycobacterium tuberculosis. After 12 months of antituberculosis treatment, the child could walk with a walker. At 37 months, he was able to walk without assistance. We conclude that spinal tuberculosis should be considered in cases of children with spinal cord-compression symptoms and an image showing an extraspinal abscess. Early diagnosis and prompt treatment are critical for maximizing a functional recovery.

The most common neurological complications associated with tuberous sclerosis complex (TSC) include intractable seizures that begin in infancy and subependymal giant cell astrocytoma (SEGA) complicated by hydrocephalus with increasing age. Information on SEGA growth of TSC patients is limited. This study aimed to examine the TSC-SEGA growth rates by periodic neuroimaging. This study evaluated the TSC-SEGA growth rates by serial neuroimaging. Fifty-eight patients with TSC underwent systematic evaluation, including a review of medical history and serial brain neuroimaging. While magnetic resonance imaging was more sensitive in detecting cortical tubers than computed tomography (73.1 vs. 0 %, p

That both infiltrating macrophages and resident mesangial cells express inducible nitric oxide synthase (iNOS) and produce nitric oxide (NO) excessively is crucial to the progress of glomerulonephritis. Although several reports have mentioned the protective impacts of conjugated linoleic acid (CLA) in stimulated macrophages, the role of CLA in glomerular mesangial cells is unknown. The aim of the present study was to explore the ability of CLA to regulate iNOS expression and NO production in stimulated glomerular mesangial cells. Additionally, we evaluated the effect of CLA on activation of transcription factors which mediate iNOS expression. Exogenous CLA dose-dependently diminished iNOS mRNA and protein expression as well as NO production in lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma)-stimulated SV-40-transformed mouse mesangial cells. Electrophoretic mobility shift assay experiments demonstrated that CLA (100 microM) dramatically reduced activation of nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1) and cAMP response element binding protein (CREB) induced by LPS/IFN-gamma. Moreover, addition of 100 microM CLA significantly diminished LPS-IFN-gamma-induced protein degradation of inhibitor kappaB-alpha (IkappaB-alpha) and the protein expression of phosphorylated IkappaB-alpha in the cytosolic fraction as well as nuclear p65 expression (P < 0.05). In summary, inhibition of NF-kappaB, AP-1 and CREB activation by CLA may be associated with the molecular basis for which CLA suppresses iNOS expression and NO production in stimulated mesangial cells.

Streptococcus bovis infection is an uncommon disease during infancy and childhood. Rhabdomyolysis is frequently a complication of a viral infection in children and typically has a benign course. It has rarely been reported as a complication in cases of bacterial infection, especially those caused by S. bovis. We describe a case of life-threatening rhabdomyolysis after a bacterial infection caused by S. bovis sepsis in a previously healthy 6-year-old girl who presented to our pediatric emergency department. She had an unusually high serum creatine kinase value (peak value, 436,449 IU/L), and she was successfully treated with adequate antibiotic treatment and effective renal replacement therapy. This case illustrates that, although uncommon, S. bovis can cause serious infections during childhood. Pediatric emergency physicians should be aware that uncommon organisms may be able to cause severe infections in susceptible children associated with life-threatening rhabdomyolysis.

Extraadrenal paragangliomas are rare pediatric tumors with variable symptoms that cause difficultly in diagnosis and delayed treatment. We report the case of a 10-year-old boy who presented to the pediatric emergency department with acute chest pain and dyspnea mimicking a non-ST-segment elevation acute myocardial infarction. He was subsequently found to have an extraadrenal paraganglioma after a series of imaging and laboratory examinations. The mass was subsequently removed, and the diagnosis of extraadrenal paraganglioma was confirmed histologically. Acute coronary syndrome as the presenting feature of extraadrenal paragangliomas in pediatric population is an even rarer clinical entity.

To examine differences in clinical characteristics among children with norovirus, rotavirus, and bacterial gastroenteritis and investigate the outcomes in children with sporadic norovirus gastroenteritis. The study included patients aged 4 mo to 14 y who had acute gastroenteritis and were admitted to a tertiary care center between April 2008 and July 2009. The clinical features and laboratory findings of acute gastroenteritis were recorded. Fecal specimens were collected and tested for viruses, bacteria, and parasites. A total of 198 children (median age, 2.1 y) with acute gastroenteritis were studied. The pathogens identified included norovirus (n = 38), rotavirus (n = 47), adenovirus (n = 5), astrovirus (n = 1), bacteria (n = 43), and mixed infections (n = 7). No causative organisms were identified in 57 patients. The norovirus-infected group had a significantly higher proportion of those still vomiting 1 d after the onset of vomiting (p

OBJECTIVE: The aim of this article was to assess the usefulness of procalcitonin (PCT) as a marker for predicting dilating (grades III-V) vesicoureteral reflux (VUR) in young children with a first febrile urinary tract infection. METHODS: Children ≤2 years of age with a first febrile urinary tract infection were prospectively evaluated. Serum samples were tested for PCT at the time of admission to a tertiary hospital. All children underwent renal ultrasonography (US), Tc-dimercaptosuccinic acid renal scan, and voiding cystourethrography. The diagnostic characteristics of PCT test for acute pyelonephritis and dilating VUR were calculated. RESULTS: Of 272 children analyzed (168 boys and 104 girls; median age, 5 months), 169 (62.1%) had acute pyelonephritis. There was VUR demonstrated in 97 (35.7%), including 70 (25.7%) with dilating VUR. The median PCT value was significantly higher in children with VUR than in those without (P < 0.001). Using a PCT cutoff value of ≥1.0 ng/mL, the sensitivity and negative predictive value for predicting dilating VUR were 94.3% and 95.4%, respectively, for PCT, and 97.1% and 97.8%, respectively, for the combined PCT and US studies, whereas the positive and negative likelihood ratios were 2.03 and 0.107, respectively, for PCT, and 1.72 and 0.067, respectively, for the combined studies. By multivariate analysis, high PCT values and abnormalities on US were independent predictors of dilating VUR. CONCLUSIONS: PCT is useful for diagnosing acute pyelonephritis and predicting dilating VUR in young children with a first febrile urinary tract infection. A voiding cystourethrography is indicated only in children with high PCT values (≥1.0 ng/mL) and/or abnormalities found on a US.

BACKGROUND Delayed hematopoietic reconstitution after cord blood transplantation (CBT) may lead to increased risk of complications and longer hospitalization. Bone marrow-derived mesenchymal stem cells (MSCs) have been found to promote engraftment after hematopoietic stem cell transplantation. However, harvesting MSCs from bone marrow involves an invasive procedure. Then again, MSCs can be easily obtained from umbilical cords without harm to the donors. METHODS Umbilical cord-derived MSCs (UCMSCs) were isolated from Wharton's jelly and then ex vivo cultured. After showing normal karyotype and negative for infectious contamination, culture-expanded UCMSCs were intravenously infused into the recipients on the day of CBT. The control patients were those receiving CBT alone. Adverse effects and efficacy of intravenous UCMSCs were evaluated. RESULTS A total of five patients received cotransplantation of UCMSCs at the time of CBT. No serious adverse events were observed. The time to achieve neutrophil engraftment ranged from 7 to 13 days (median, 11 days) and platelet engraftment ranged from 22 to 41 days (median, 32 days). Compared with the nine patients receiving CBT alone, patients receiving cotransplantation of UCMSCs had significantly faster hematopoietic recovery of neutrophils and platelets (P=0.02 and 0.01, respectively). CONCLUSIONS This pilot study is the first report of cotransplantation of UCMSCs in CBT. Intravenous infusion of UCMSCs appeared to be a feasible and safe modality to enhance hematopoietic engraftment in patients receiving CBT. Further studies were warranted.

Ectopic kidney is a rare condition. Giant hydronephrosis is also an uncommon lesion in children and is usually due to ureteropelvic junction obstruction. We report a case of 7-year-old girl presenting with abdominal fullness. The imaging characteristics of magnetic resonance urography of the lesions are reported. The findings from the radiologic investigations were suggestive of a dysplastic ectopic pelvic kidney with giant hydronephrosis. Subsequent surgery confirmed the diagnosis. An ectopic kidney with giant hydronehrosis is an extremely rare condition in children and can present as an asymptomatic abdominal mass. A careful survey for other structural anomalies is mandatory in such cases.

The association between neonatal jaundice and childhood asthma is a new finding of two reports. The purpose of the study was to verify their results.Data from 11,321 children were collected from the National Health Insurance Research Database. Their claims data were evaluated from birth to 10 yr old. Children were analyzed as case (those with neonatal jaundice) and controls (those without neonatal jaundice). The diagnostic criteria for asthma were as follows: at least four asthma diagnoses at outpatient services and emergency department (ED), or one asthma diagnosis during an admission. In children fitting the asthma criteria, those with no asthma diagnosis after 1 yr of age were excluded. Mantel-Haenszel's odds ratios were calculated after adjustment for the following confounders: preterm/low birth weight, neonatal infection, other respiratory conditions, other birth conditions, and gender. Asthma rate, onset time, the use of drugs, upper respiratory infection and lower respiratory infection (LRI) rates, hospital admission/ED visit rates, and the effect of phototherapy were evaluated.After adjustment for the confounding factors, the rate of asthma was higher in icteric children (OR: 1.64, 95% CI 1.36-1.98, p0.001), and the influence in females was stronger. There still was an association between neonatal jaundice and late onset asthma (asthma onset after 3 yr of age). In asthmatic children, those with neonatal jaundice have increased asthma onset rate before age 6, increased use of inhalant steroids, LRI rates, and ED visits for respiratory disease.Neonatal jaundice increased the rate and severity of childhood asthma in subjects aged up to 10 yr and may be a risk factor for childhood asthma.

Acute bacterial meningitis (ABM) is a serious disease with severe neurological sequelae. The intense calcium-mediated microglial activation and subsequently pro-inflammatory cytokine release plays an important role in eliciting ABM-related oxidative damage. Considering resveratrol possesses significant anti-inflammatory and anti-oxidative properties, the present study aims to determine whether resveratrol would exert beneficial effects on hippocampal neurons following ABM. ABM was induced by inoculating Klebsiella pneumoniae into adult rats intraventricularly. The time-of-flight secondary ion mass spectrometry (TOF-SIMS), Griffonia simplicifolia isolectin-B4 (GSA-IB4) and ionized calcium binding adaptor molecule 1 (Iba1) immunohistochemistry, enzyme-linked immunosorbent assay as well as malondialdehyde (MDA) measurement were used to examine the calcium expression, microglial activation, pro-inflammatory cytokine level, and extent of oxidative stress, respectively. In ABM rats, strong calcium signaling associated with enhanced microglial activation was observed in hippocampus. Increased microglial expression was coincided with intense production of pro-inflammatory cytokines and oxidative damage. However, in rats receiving resveratrol after ABM, the calcium intensity, microglial activation, pro-inflammatory cytokine and MDA levels were all significantly decreased. Quantitative data showed that much more hippocampal neurons were survived in resveratrol-treated rats following ABM. As resveratrol successfully rescues hippocampal neurons from ABM by suppressing the calcium-mediated microglial activation, therapeutic use of resveratrol may act as a promising strategy to counteract the ABM-induced neurological damage.

An ectopic ureter draining into the seminal vesicle or vas deferens in males is a very rare anomaly and is usually associated with renal dysplasia or agenesis. An ectopic ureter associated with a dysplastic kidney is not usually a suspected cause during clinical evaluation of children with abdominal pain. This report presents a rare case of an ectopic ureter associated with a dysplastic kidney with an acute infection in a previously healthy 12-year-old boy, demonstrated by magnetic resonance imaging. He presented with abdominal pain that mimicked acute appendicitis-like symptoms which was subsequently complicated by epididymitis manifesting as an acute scrotum. Clinicians should consider including an ectopic ureter in the differential diagnosis of children presenting with acute abdomen.

Supplementary consumption of probiotics may temporarily alter the intestinal microflora of infants and children, thereby preventing and treating allergic disorders.To compare the clinical efficacy of levocetirizine with that of levocetirizine plus Lactobacillus johnsonii EM1 (Lj EM1) for treating perennial allergic rhinitis (PAR) in children.Sixty-three children aged 7-12 years fulfilled the entry criteria for the study and had moderate to severe PAR of at least 1 year's duration. The treatment followed a randomized, open-label crossover design: all subjects were randomized to 2 crossover treatment regimens of levocetirizine with Lj EM1 (group 1) or levocetirizine alone (group 2) for 12 weeks; subsequently, treatments were reversed for a further 12 weeks. The effects of the 2 regimens were compared using the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) and the total symptom score (TSS) from diary cards. The parameters evaluated were nasal peak expiratory flow rate (nPEFR), FVC, FEV1, serum immunoglobulin E (IgE), mite-specific IgE, eosinophilic cationic protein (ECP), resistin, blood eosinophils, eosinophil percentage in nasal smears, IL-4, IL-10, interferon-γ (IFN-γ), and transforming growth factor-β (TGF-β).After the first 12 weeks of treatment, TSS in both groups had improved progressively compared with that in the run-in period. Both groups had improved TSS at weeks 4, 8, and 12 (P0.05), and group 1 was more efficacious than group 2 at week 4 (P=0.014), week 8 (P=0.011), and week 12 (P0.009). During the second 12-week period, group 2 showed continual and progressive improvement, while group 1 did not. The PRQLQ scores were significantly decreased in both groups (P0.05), but there was no statistically significant difference between the 2 groups (P=0.446). The eosinophil percentage in nasal smears decreased in both groups compared with that in the run-in period, and significant differences were detected in groups 2 and 1at 16 and 24 weeks of treatment, respectively (P0.05). Both groups showed significant improvement in nPEFR at weeks 4, 8, 12, 16, and 24 (P0.01), and the treatment for group 1 appeared to be more efficacious than that for group 2 at weeks 12, 16, and 20 (P0.05). FVC and FEV1 were improved in both groups at weeks 8 through 24 (P0.05), but there was no significant difference between the 2 groups. In cytokine measurements, IFN-γ and IL-10 increased significantly and IL-4 decreased significantly in both groups, while elevation of TGF-β was seen only in group 1 at 12 weeks (P0.001). However, the difference in TGF-β disappeared after 24 weeks treatment. There was no difference in serum resistin levels. No serious adverse events were recorded in either treatment group.The 24-week, 2-phase, crossover treatment program showed that levocetirizine plus Lj EM1 was more effective for PAR than levocetirizine and that this difference persisted for at least 3 months after discontinuation of Lj EM1.

The allergy is dependent on the balance between Th1 and Th2. The fungal immunodulatory protein (FIP- fve ) was isolated from Flammulina velutipes. FIP- fve has been demonstrated to skew the response to Th1 cytokine production. We investigated whether oral administrations of FIP- fve inhibited allergen (OVA)-induced chronic airway inflammation in the mouse asthma model. After intranasal challenge with OVA, the airway inflammation and hyperresponsiveness were determined by bronchoalveolar lavage fluid (BALF) analysis and ELISA assay. Both pre-treated and post-treated with FIP- fve suppressed the airway hyperresponsiveness by methacholine challenge and significantly decreased the number of infiltrating inflammatory cells and Th2 cytokines in bronchoalveolar lavage fluid (BALF) and serum compared with the OVA sensitized mice. In addition, FIP- fve reduced OVA-specific IgE levels in serum. FIP- fve markedly alleviated the OVA-induced airway hyperresponsiveness (AHR) to inhaled methacholine. Based on lung histopathological studies using hematoxylin and Liu’s staining, FIP- fve inhibited inflammatory cell infiltration compared with the OVA-sensitized mice. Oral FIP- fve had an anti-inflammatory effect on OVA-induced airway inflammations and might posses the potential for alternative therapy for allergic airway diseases.

Purulent pericarditis is an extremely rare complication of invasive Streptococcus pneumoniae infection among children in the antibiotic era, and its mortality remains high if left untreated. This report involves a 4½-year-old girl who presented to our emergency department with productive cough, shortness of breath, and left-sided chest pain with a diagnosis of pneumococcal pneumonia. She subsequently developed life-threatening conditions including bilateral empyema with respiratory failure, purulent pericarditis, and multiple organ failure leading to death. The case highlights that purulent pericarditis is a rare yet possible disorder complicating pneumococcal disease in the antibiotic era. The increase in strains resistant to penicillin should alert emergency physicians to the potential for reemergence of pneumococcal pericarditis in children.

Objectives Rotavirus and norovirus are the two most common causes of acute viral gastroenteritis in children. This study aimed to explore the association of serum interleukin-6 (IL-6) and interleukin-10 (IL-10) levels and the clinical features in children with rotavirus and norovirus gastroenteritis. Methods This prospective study enrolled 168 acute gastroenteritis patients admitted to a tertiary care center. Peripheral blood samples were collected for IL-6 and IL-10 assays within the first 72 h of illness. The diagnostic performance of clinical tests was estimated using the receiver operating characteristic (ROC) analysis. Binary logistic regression modeling was performed to examine the predictive variables. Results Serum IL-6 and IL-10 were measured in children with rotavirus infection ( n = 30), norovirus infection ( n = 25), Salmonella infection ( n = 26), and in 11 healthy controls. There were significant higher degrees of severity of illness and levels of IL-10 in the rotavirus group as compared to the norovirus group. The binary logistic regression analysis revealed that both the ANC and maximum body temperature (BT) were significant clinical predictors for discriminating rotavirus and norovirus gastroenteritis. The ROC curve to evaluate the accuracy of logistic regression model had an AUC of 0.847 (95% CI: 0.741–0.952, p Conclusions IL-10 shows a significant discriminating ability between rotavirus and norovirus infection. A model incorporating maximum BT and ANC can help pediatricians to distinguish between rotavirus and norovirus in children with a suspected viral gastroenteritis.

Acute bacterial meningitis caused by Klebsiella pneumoniae (K. pneumoniae) is a major health threat with a high mortality rate and severe neuro-cognitive sequelae. The intense pro-inflammatory cytokine released from calcium-mediated microglial activation plays an important role in eliciting neuronal damage in the hippocampal region. Considering melatonin possesses anti-inflammatory and immuno-modulatory properties, the present study determined whether melatonin can effectively decrease inflammatory responses and prevent hippocampal damage in animals subjected to K. pneumoniae. Adult rats inoculated with K. pneumoniae received a melatonin injection immediately thereafter at doses of 5, 25, 50, or 100 mg/kg. Following 24 h of survival, all experimental animals were processed for time-of-flight secondary ion mass spectrometry (for detecting glial calcium intensity), isolectin-B4 histochemistry (reliable marker for microglial activation), pro-inflammatory cytokine measurement as well as cytochrome oxidase and in situ dUTP end-labeling (representing neuronal bio-energetic status and apoptotic changes, respectively). Results indicate that in K. pneumoniae-infected rats, numerous calcium-enriched microglia, enhanced pro-inflammatory cytokine, and various apoptotic neurons with low bio-energetic activity were detected in hippocampus. Following melatonin administration, however, all parameters including glial calcium intensity, microglial activation, pro-inflammatory cytokine levels, and number of apoptotic neurons were successfully decreased with maximal change observed at a melatonin dose of 100 mg/kg. Enzymatic data corresponded well with above findings in which all surviving neurons displayed high bio-energetic activity. As effectively reducing glia-mediated inflammatory response is neuro-protective to hippocampal neurons, the present study supports the clinical use of melatonin as a potential therapeutic agent to counteract K. pneumoniae meningitis-induced neuro-cognitive damage.

Acute bacterial meningitis caused by Klebsiella pneumoniae (K. pneumoniae) is a major health threat with a high mortality rate and severe neuro-cognitive sequelae. The intense pro-inflammatory cytokine released from calcium-mediated microglial activation plays an important role in eliciting neuronal damage in the hippocampal region. Considering melatonin possesses anti-inflammatory and immuno-modulatory properties, the present study determined whether melatonin can effectively decrease inflammatory responses and prevent hippocampal damage in animals subjected to K. pneumoniae. Adult rats inoculated with K. pneumoniae received a melatonin injection immediately thereafter at doses of 5, 25, 50, or 100 mg/kg. Following 24 h of survival, all experimental animals were processed for time-of-flight secondary ion mass spectrometry (for detecting glial calcium intensity), isolectin-B4 histochemistry (reliable marker for microglial activation), pro-inflammatory cytokine measurement as well as cytochrome oxidase and in situ dUTP end-labeling (representing neuronal bio-energetic status and apoptotic changes, respectively). Results indicate that in K. pneumoniae-infected rats, numerous calcium-enriched microglia, enhanced pro-inflammatory cytokine, and various apoptotic neurons with low bio-energetic activity were detected in hippocampus. Following melatonin administration, however, all parameters including glial calcium intensity, microglial activation, pro-inflammatory cytokine levels, and number of apoptotic neurons were successfully decreased with maximal change observed at a melatonin dose of 100 mg/kg. Enzymatic data corresponded well with above findings in which all surviving neurons displayed high bio-energetic activity. As effectively reducing glia-mediated inflammatory response is neuro-protective to hippocampal neurons, the present study supports the clinical use of melatonin as a potential therapeutic agent to counteract K. pneumoniae meningitis-induced neuro-cognitive damage.

Background: Interleukin (IL)-8 acts as a potent neutrophils chemoattractant responsible for the migration of neutrophils into the infected renal tissue to protect against invading pathogens. The aim of this study was to assess the role of IL-8 on acute-phase pyelonephritis and later renal scarring in children. Patients and Methods: A total of 124 children with a first-time febrile urinary tract infection (UTI) were studied. The diagnosis of acute pyelonephritis was confirmed by 99m Tc-dimercaptosuccinic acid (DMSA) renal scan. Serum and urine samples were obtained from 124 children with UTI and 20 healthy children for IL-8 measurement. Results: The 124 children were divided into acute pyelonephritis (n = 70) and lower UTI (n = 54) groups according to the results of DMSA scans. The initial serum and urine IL-8 values of children with acute pyelonephritis were significantly higher when compared with lower UTI and healthy controls (all P < 0.001). Renal scarring was seen in 26 (38.8%) of these 67 children with acute pyelonephritis at follow-up DMSA scans. Both the initial serum and urine IL-8 concentrations were significantly higher in children with renal scarring than in those without (both P < 0.001). The mean age of children with renal scarring was also significantly lower than those without scarring (P = 0.004). Multivariate analysis showed that the highest initial IL-8 values, age

Background Cordyceps militaris is a well-known fungus with immunomodulatory activity. It is generally used in traditional Chinese medicine to treat hemoptysis, bronchial or lung inflammation, and urogenital disorders. The purpose of our study was to evaluate the effect of cultivated C. militaris on airway inflammation in a mouse asthma model. Methods BALB/c mice were sensitized with intraperitoneal ovalbumin (OVA) on Days 0 and 14, and were then given intranasal OVA on Day 14 and Days 25-27. Randomized treatment groups of sensitized mice were administered C. militaris , prednisolone, montelukast, or placebo by gavage from Days 15-27. Airway hyperreactivity to aerosolized methacholine was determined. Bronchoalveolar lavage fluid and serum were analyzed to assess airway inflammation. Results OVA-sensitized mice developed a significant airway inflammatory response that was inhibited by prednisolone and montelukast, whilst C. militaris reduced airway inflammation less effectively. Airway hyperresponsiveness to methacholine was observed in OVA-sensitized mice and was reversed by both prednisolone and montelukast. C. militaris initially reversed airway hyperreactivity, but this effect disappeared at higher methacholine doses. Conclusion C. militaris can modulate airway inflammation in asthma, but it is less effective than prednisolone or montelukast. These results demonstrate that C. militaris is unable to adequately block the potent mediators of asthmatic airway inflammation.

Acute pyelonephritis is a common infectious disease in children and can result in permanent renal damage. Interleukin-6 (IL-6) is an important mediator of inflammation in response to bacterial infection. This study investigated the potential relationship between acute-phase IL-6 and subsequent renal scarring in children with a first time febrile acute pyelonephritis.In total, 79 children (age range 1-120 months) with a first time febrile urinary tract infection (UTI) were included. The diagnosis of acute pyelonephritis was confirmed by (99m)Tc-dimercaptosuccinic acid (DMSA) renal scan. Serum and urine samples were collected for IL-6 measurement by enzyme-linked immunosorbent assay before antibiotic treatment for the infection.The 79 children were divided into acute pyelonephritis (n=45) and lower UTI (n=34) groups according to the findings of DMSA scans. The initial serum and urine IL-6 levels of children with acute pyelonephritis were significantly higher compared with lower UTI (p0.001). Renal scarring was detected at the follow-up DMSA scans in 15 (34.1%) of the 44 children with acute pyelonephritis. Both serum and urine IL-6 levels during the acute phase of pyelonephritis were significantly higher in children with renal scarring than in those without (p=0.005 and p = 0.002). The median age of children with renal scarring was significantly lower than those without (p=0.034). Multiple regression analysis showed that higher initial serum and urine IL-6 levels and a younger age were associated with renal scarring.These results demonstrate that in younger children with a first time febrile acute pyelonephritis, elevations of the acute-phase serum and urine IL-6 levels were correlated with an increased risk of subsequent renal scarring.