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We examined the amount of gelatinases (matrix metalloproteinase-2 and -9 [MMP-2 and MMP-9] in a series of chondral, meniscal, and synovial cultures of early osteoarthritis (OA) after treatment with or without catabolic cytokines. These included interleukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), and pharmacological agents, including plasmin/serine proteinase antagonist aprotinin, protein synthesis inhibitor cycloheximide, and protein kinase C (PKC) inhibitors staurosporine, H7, and Gö6976 for investigation of their effects on MMP-2 and -9 production in OA. Gelatin zymography revealed that IL-alpha, TNF-alpha, and LPS could elevate MMP-2 secretion in all tissue cultures and also increase MMP-9 production in all synovial and some meniscal cultures. In contrast, aprotinin, cycloheximide, staurosporine, H7, and Gö6976 could suppress MMP-2 secretion in all tissue cultures and also decrease MMP-9 production in all synovial and some meniscal cultures. Our data indicate that catabolic cytokines and LPS may promote tissue destruction and disintegration of extracellular matrix in early OA. Agents that target on the PKC pathway, plasmin/serine proteinase or protein synthesis for MMP-2 and -9 in early OA may inhibit the production of MMPs. These findings might contribute to the design of more efficacious therapies.

Background: Clinically, gouty arthritis is associated with severe inflammation, such as pain, swelling and erythema of the joints. Gelatinase A and B (matrix metalloproteinase-2 and -9, MMP-2 and -9) participate in the degradation of the extracellular matrix (ECM) components in a variety of arthritis, especially in the inflammatory arthritis. Methods: We examined the levels of MMP-2 and -9 in 40 synovial fluids (SFs) from the knee joints of 24 patients with gouty arthritis and compared them with the clinical and laboratory variables of inflammation. Results: Gelatin zymography revealed that not only activated MMP-2 levels but also proMMP-9 levels in SF from the knee joints of gouty arthritis were associated with the local arthritis activity scores (LAS) (p

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.

Primary lung tumors are rare in children, and primary bronchopulmonary leiomyosarcomas are very rare in children, with only 10 cases reported in the English-language literature. We report on the eleventh case of primary bronchopulmonary leiomyosarcoma in a child, and it is the first case in Taiwan, and also in Asia. In addition, this is the second case of this tumor arising in the left main bronchus. Before the present case, there were only 2 cases of this tumor in the main bronchus: one was in the right main-stem bronchus, and the other in the left-stem main bronchus. Ours is the second case showing pleural effusion. Chest roentgenogram and bronchoscopy are helpful in the diagnosis of primary bronchopulmonary tumors, but a definitive diagnosis can only be made by biopsy. The tumor is potentially curable if total excision is possible; irradiation has little therapeutic value, and early excision offers the only hope of cure. The child is alive and well 19 months after pneumonectomy, without having received radiotherapy or chemotherapy.

Asthma is a major public health concern. Its greatest risk factor is house dust mite (HDM). Dermatophagoides microceras (Der m) is a type of HDM, and in central Taiwan, there is approximately 80% prevalence of sensitization to Der m. FIP-fve is a fungal immunomodulatory protein (FIP) isolated from the fungus Flammulina velutipes, and exhibits anti-inflammatory properties. To investigate whether FIP-fve affects Der m-induced asthma and inflammation, we evaluated hyper-responsiveness (AHR), pathological changes, and cytokines in mice. We demonstrated that oral FIP-fve decreased Der m-induced airway AHR, airway inflammation, cell infiltration, and expression of cytokines in the bronchoalveolar lavage fluid of Balb/c mice. The results of this study suggest that FIP-fve suppresses asthma, inflammation, and respiratory pathogenesis stimulated by Der m. FIP-fve is able to maintain immunomodulatory activity even in simulated gastric fluid and intestinal fluid. FIP-fve could be a safe and stable agent for suppression of allergic asthma.

Jeng-Dau Tsai,1,2 Cheng-Li Lin,3,4 Cheng-Chieh Lin,5–7 Fung-Chang Sung,3,4,7,* Ko-Huang Lue1,2,* 1Institute of Medicine, Chung Shan Medical University Hospital, 2Department of Pediatrics, Chung Shan Medical University and Hospital, 3Institute of Clinical and Medical Science, China Medical University, 4Management Office for Health Data, China Medical University Hospital, 5Department of Family Medicine, China Medical University School of Medicine, 6Division of Family Medicine, China Medical University Hospital, 7Department of Healthcare Administration, College of Health Science, Asia University, Taichung, Taiwan *These authors contributed equally to this work Background: Systemic lupus erythematosus (SLE) affects central and peripheral nervous systems, manifesting neuropsychiatric disorders that vary from subtle signs to life-threatening complications. This study compared the risk of epilepsy between a general population and patients with SLE.Methods: From the national insurance claims data of the Taiwan National Health Research Institutes, we identified 32,301patients with newly diagnosed SLE from 1997–2010and, for comparison, 129,204randomly selected people without SLE; the frequencies of both groups were matched by sex, age, and diagnosis date. The incidence of epilepsy was estimated for both cohorts by the end of 2010. Results: The incidence of epilepsy was 2.86-fold higher in the SLE cohort than in the non-SLE cohort (9.10per 10,000person-years versus 3.18per 10,000person-years), with a Cox method estimated adjusted hazard ratio (aHR) of 2.33(95% confidence interval [CI] =1.89–2.88) for the SLE cohort. The incidence increased with age in the non-SLE cohort, while it decreased with the increase of age in the SLE cohort. Compared with the non-SLE cohort, the age-specific aHR of epilepsy for the SLE cohort decreased from 8.05(95% CI =4.30–15.0) for those aged ≤20years to 0.90(95% CI =0.57–1.42) for those aged 60years and above (P=0.01). Comorbidities that had a significant association with epilepsy included infarction (aHR =7.62), intracerebral hemorrhage (aHR =5.75), aseptic meningoencephalitis (aHR =5.35), and psychiatric disorder (aHR =3.31).Conclusion: Patients with SLE are at higher risk of epilepsy than the general population, especially younger SLE patients. Neurologic comorbidities and psychiatric disorders increase the epilepsy risk further. Keywords: epilepsy, incidence, lupus, health insurance data, cohort study

There is a distinct lack of knowledge on the prevalence of skin disorders in Tuvalu. The aim of the current study was to assess the prevalence of cutaneous diseases and to evaluate access dermatological care in Tuvalu. Cutaneous disorders in the people of Tuvalu between 2009 and 2012 were examined. The most common skin conditions were eczema/dermatitis, superficial fungal infections, impetigo, carbuncles, furuncles, folliculitis, acne, scabies, warts and keloids. Infrequent skin conditions included infectious granulomatous disease, albinism, actinic keratosis, skin cancer, cutaneous lupus erythematosus and mammary Paget's disease, which required medical attention. This is the first epidemiological report on skin disorders in the southwest Pacific Island, Tuvalu.

Respiratory syncytial virus (RSV) causes bronchiolitis in children followed by inflammation and asthma-like symptoms. The development of preventive therapy for this virus continues to pose a challenge. Fungal immunomodulatory proteins (FIPs) exhibit anti-inflammatory function. FIP-fve is an immunomodulatory protein isolated from Flammulina velutipes. To determine whether FIP-fve affects the infection or consequence of immunity of RSV, we investigated viral titers of RSV and inflammatory cytokine levels in vivo and in vitro. Oral FIP-fve decreased RSV-induced airway hyperresponsiveness (AHR), airway inflammation, and IL-6 expression in bronchoalveolar lavage fluid (BALF) of BALB/c mice. RSV replication and interleukin 6 (IL-6) levels in RSV-infected HEp-2 cells were compared before and after FIP-fve treatment. FIP-fve inhibited viral titers on plaque assay and Western blot, as well as inhibited RSV-stimulated expression of IL-6 on ELISA and RT-PCR. The results of this study suggested that FIP-fve decreases RSV replication, RSV-induced inflammation and respiratory pathogenesis. FIP-fve is a widely used, natural compound from F.velutipes that may be a safe agent for viral prevention and even therapy.

FIP-fve is an immunomodulatory protein isolated from Flammulina velutipes that possesses anti-inflammatory and immunomodulatory activities. However, little is known about its anticancer effects. It is suppressed cell proliferation of A549 lung cancer cells on MTT assay following 48 h treatment of FIP-fve. FIP-fve treatment also resulted in cell cycle arrest but not apoptosis on flow cytometry. This immunomodulatory protein was observed to increase p53 expression, as well as the expression of its downstream gene p21, on Western blot. FIP-fve inhibited migration of A549 cells on wound healing assay and decreased filopodia fiber formation on labeling with Texas Red-X phalloidin. To confirm the effect of FIP-fve on the role of Rac1 in filopodia formation, we investigated the activity of Rac1 in A549 cells following FIP-fve treatment. FIP-fve inhibited EGF-induced activation of Rac1. We demonstrated that FIP-fve decreases RACGAP1 mRNA and protein levels on RT-PCR and Western blot. In addition, the reporter activity of RACGAP1 was reduced by FIP-fve on RacGAP1 promoter assay. Silencing of RacGAP1 decreased cell migration, and overexpression of RacGAP1 increased cell migration in A549 cells. In conclusion, FIP-fve inhibits lung cancer cell migration via RacGAP1 and suppresses the proliferation of A549 via p53 activation pathway.

Background The co-effect of asthma and obstructive sleep apnea (OSA) on sleep quality among children remained unclear. Objective To compare sleep quality and emotional/behavioral problems among asthmatic and non-asthmatic children with or without moderate to severe obstructive sleep apnea. Method An AHI-range-matched BMI-range-matched cross-sectional design was used to examine polysomnographic evaluation and emotional/behavioral problems in 102 non-obese children aged between 6 and 12 years old, categorized as with or without asthma and sleep disordered breathing. Results Asthmatic children in AHI ≤ 5/h group revealed a significantly longer sleep latency, a greater leg movement index (LMI), and a lower ratio of slow wave sleep compared with non-asthmatic AHI ≤ 5/h group. Compared with non-asthmatic AHI > 5/h group, asthmatic children displayed a higher ratio of REM sleep, sleep stage 1 and 2, a lower ratio of slow wave sleep, as well as a greater respiratory arousal index and LMI. There was no significant difference in emotional/behavior problems among groups. Conclusion Sleep disturbance exists in asthmatic children with or without moderate to severe obstructive sleep apnea. Non-obese asthmatic children had less slow wave sleep compared with non-asthmatic children. We might recommend that sleep quality could be noticed and evaluated in children with asthma.

Background This study evaluates the association between neonatal jaundice and childhood allergic rhinitis (AR). Methods Eleven thousand three hundred twenty-eight children were collected from the National Health Insurance Research Database in Taiwan. Their claims data were evaluated from birth to 10 years of age, and they were assigned to either the study (with neonatal jaundice) or the control (without neonatal jaundice) group. The diagnostic criteria for AR were at least three diagnoses of AR at outpatient services, one diagnosis of AR during an admission, or one diagnosis of AR in an emergency department. Mantel-Haenszel odds ratios (ORs) were calculated after adjustment for the following confounders: preterm/low birth weight, neonatal infection, other respiratory conditions, other birth conditions, and gender. AR rate, AR onset time, the use of oral antihistamines/nasal corticosteroids, outpatient visit frequency for AR, lower respiratory infection (LRI) rates, sinusitis/otitis media/conjunctivitis rates, and the effect of phototherapy were evaluated. Results After adjustment for the confounding factors, the rate of AR was higher in icteric children (OR, 1.46; 95% confidence interval, 1.24~1.72). There was a higher incidence of AR in children Conclusion Neonatal jaundice increased the rate and complications of childhood AR in subjects aged up to 10 years and may be a risk factor for childhood AR.

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.

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MicroRNAs are endogenous small non-coding RNAs about 21 nucleotides in length that inhibit the expression of target genes primarily at the post-transcriptional level. The target recognition of microARN is sequence-specific and requires a partial complementarity between the microRNA and target sequences that are present on the mRNA molecules. microRNAs are part of an effector complex, miRISC, containing multiple proteins which can participate to a repression of translation and/or promotes destabilization of the target mRNA. The mechanism of microRNA silencing is not completely understood to date, but it is assumed that it is globally less potent than that of siRNA acting on perfect targets. By using fluorescent proteins expressing reporter plasmids and flow cytometry, we observed an efficient silencing by microRNA which does not require more active complexes than the perfect target silencing and cannot be easily saturated. This suggests that in cells in culture, microRNA silencing works in a catalytic manner leading to mRNA degradation. In addition, our data also indicates that the efficiency of microRNA silencing is variable among cells and can be almost completely abrogated under some conditions contrary to the siRNA silencing which is active in all cells. As we observed that the protein Ago2 is the only member of Ago family that is implicated in the microRNA silencing, it follows that the regulation of microRNA silencing acts after the formation of the core complex (Ago2/small RNA). So the difference between the silencing in the perfect and imperfect mode are not what is usually proposed, but pertain to a level of cellular control, which remains to be deciphered.; Les microARN constituent une classe de petits ARN non codants d’une vingtaine de nucléotides, issus de transcrits cellulaires, qui inhibent l’expression de gènes cibles au niveau post-transcriptionnel. Chez les mammifères, bien qu’ils puissent agir sur une cible parfaitement complémentaire (mode parfait), les microARN ont presqu’exclusivement des cibles partiellement complémentaires (mode imparfait). Puisqu’en mode imparfait une coupure endonucléolytique de la cible est impossible, il est généralement proposé que le mode imparfait soit moins efficace que le mode parfait : conduisant à un silencing moins efficace, nécessitant plus de complexes effecteurs (miRISC) et facilement saturable par une augmentation du nombre de cible. Dans ce travail j’ai développé une approche expérimentale reposant sur l’expression de protéines fluorescentes pour mesurer précisément le silencing au niveau de chaque cellule. J’ai fait trois observations inattendues sur l’efficacité de la régulation par les microARN : i) le silencing en mode parfait et imparfait nécessite des quantités similaires de petit ARN, ii) une augmentation, même très importante, de l’expression du gène cible ne lui permet pas d’échapper à la régulation, iii) le silencing n’est pas intrinsèquement plus faible en mode imparfait (qu’en mode parfait) mais n’est pas actif dans toutes les cellules. Si les deux premiers points sont facilement explicables dans le cadre de l’induction de la dégradation de l’ARNm cible sur un mode catalytique via la déadénylation de l’ARNm, le troisième indique l’existence d’une régulation forte du silencing qui est spécifique du mode imparfait. De plus, comme dans les deux modes le silencing dépend principalement du même partenaire, Ago2, cette régulation intervient après l’assemblage du complexe minimal (Ago2/petit ARN). Ainsi, les différences entre les modes parfait et imparfait ne se situent pas au niveau proposé puisque lorsque la cellule est compétente, leurs efficacités sont comparables. Par contre, mes travaux mettent en évidence l’existence d’un contrôle de la régulation en mode imparfait dont la nature reste à préciser.

Selaginella tamariscina is a traditional medicinal plant for treatment of some advanced cancers in the Orient. However, the effect of S. tamariscina on metastasis of osteosarcoma and the underlying mechanism remain unclear. We tested the hypothesis that S. tamariscina suppresses cellular motility, invasion and migration and also investigated its signaling pathways. This study demonstrates that S. tamariscina, at a range of concentrations (from 0 to 50 μg/mL), concentration-dependently inhibited the migration/invasion capacities of three osteosarcoma cell lines without cytotoxic effects. Zymographic and western blot analyses revealed that S. tamariscina inhibited the matrix metalloproteinase (MMP)-2 and MMP-9 enzyme activity, as well as protein expression. Western blot analysis also showed that S. tamariscina inhibits phosphorylation of p38 and Akt. Furthermore, SB203580 (p38 inhibitor) and LY294002 (PI3K inhibitor) showed the similar effects as S. tamariscina in U2OS cells. In conclusion, S. tamariscina possesses an antimetastatic activity in osteosarcoma cells by down-regulating MMP-2 and MMP-9 secretions and increasing TIMP-1 and TIMP-2 expressions through p38 and Akt-dependent pathways. S. tamariscina may be a powerful candidate to develop a preventive agent for osteosarcoma metastasis.

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.

Autophagic cell death is considered a self-destructive process that results from large amounts of autophagic flux. In our previous study, GMI, a recombinant fungal immunomodulatory protein cloned from Ganoderma microsporum, induced autophagic cell death in lung cancer cells. The aim of this study was to examine the role of autophagosome accumulation in GMI-mediated cell death.Western blot analysis, flow cytometry and confocal microscopy were used to evaluate the effects of different treatments, including silencing of ATP6V0A1 by use of short hairpin RNAi, on GMI-mediated cell death, lung cancer cell viability and autophagosome accumulation in vitro.Lysosome inhibitors bafilomycin-A1 and chloroquine increased GMI-mediated autophagic cell death. GMI and bafilomycin-A1 co-treatment induced the accumulation of large amounts of autophagosomes, but did not significantly induce apoptosis. GMI elicited autophagy through the PKB (Akt)/mammalian target of rapamycin signalling pathway. Silencing of ATP6V0A1, one subunit of vesicular H(+)-ATPases (V-ATPases) that mediates lysosome acidification, spontaneously induced autophagosome accumulation, but did not affect lysosome acidity. GMI-mediated autophagosome accumulation and cytotoxicity was increased in shATP6V0A1 lung cancer cells. Furthermore, ATP6V0A1 silencing decreased autophagosome and lysosome fusion in GMI-treated CaLu-1/GFP-LC3 lung cancer cells.We demonstrated that autophagosome accumulation induces autophagic cell death in a GMI treatment model, and ATP6V0A1 plays an important role in mediating autophagosome-lysosome fusion. Our findings provide new insights into the mechanisms involved in the induction of autophagic cell death.

Phyllanthus urinaria is widely used as anti-inflammatory, antiviral, antibacterial, and anti-hepatotoxic medicines in almost every tropical country. However, scientific evidence supporting its use in cancer metastasis is limited, particularly osteosarcoma. We investigated the effect of P. urinaria extract (PUE) on cell viability, invasion, and migration in the human osteosarcoma Saos-2 cell line, and looked at the impact of PUE on several relevant proteases and signaling pathways. This study demonstrates that PUE, at a range of concentrations (from 0 to 100 μg/ml), concentration-dependently inhibited the migration/invasion capacities of Saos-2 without cytotoxic effects. Zymographic and western blot analyses revealed that PUE inhibited the urokinase-type plasminogen activator (u-PA) and matrix metalloproteinase-2 (MMP-2) enzyme activity, as well as protein expression. Western blot analysis also showed that PUE inhibits phosphorylation of ERK1/2 and Akt. Testing of mRNA level, quantitative real-time PCR, and promoter assays evaluated the inhibitory effects of PUE on u-PA expression in Saos-2 cells. The chromatin immunoprecipitation (ChIP) assay was reactive to the transcription protein SP-1, which was inhibited by PUE. In conclusion, PUE suppresses human osteosarcoma Saos-2 cell invasion and migration by transcriptionally inhibiting u-PA via ERK and Akt signaling pathways. Therefore, PUE produces anti-metastatic activity in Saos-2 cells.

FIP-fve is a protein that is isolated from Flammulina velutipes . Its known immunomodulatory activities are elicitation of the production of type II interferon from human peripheral mononuclear cells (hPBMCs) and hemagglutination. How the target receptors mediate activation of FIP-fve-induced immunomodulatory effects remains to be elucidated. This study postulates the three-dimensional structures to determine whether the carbohydrate binding module family 34 (CBM-34) on FIP-fve is conserved to site N of Thermoactinomyces vulgaris R-47 α-amylase I. Experimental site-directed mutagenesis data as well as ligand-specific binding competition assay are adopted to identify the key residues W24, T28, D34, T90, I91, and W111 of FIP-fve that participate in binding to polysaccharides that are linked to the membrane of immune cells. Treatments of hPBMCs with tunicamycin and deglycosylation enzymes that removed the carbohydrate moieties reduced the secretion of IFN-γ induction from hPBMCs. In conclusion, the experiments herein demonstrated the ligand-binding CBM-34 on FIP-fve and ligand-like glycoproteins on the surface of hPBMCs must be required to induce physiological immunomodulatory effects.

Epidemiological research underpins the importance of effective health-care strategies for adolescents. This descriptive study compares the 10 most common diseases among Taiwanese adolescents for 2000 and 2009.Data for a total of 69,594 visits in 2000 and 65,802 visits in 2009 by adolescents aged between 10 and 20 years were collected from the National Health Insurance Research Database. A maximum of three outpatient diagnostic codes (International Classification of Disease, ninth revision) could be listed for every visit. The data categories were: principal diagnosis, patient age, and physician specialty. The middle adolescent age group utilized the least amount of medical services. Respiratory (46.2% in 2000, 40.5% in 2009) and digestive (16.5% in 2000 and 16.9% in 2009) tracts were the leading two diagnostic categories for adolescent ambulatory visits. Teeth (6.8%, 6.1%) and eye (4.0%, 3.1%) problems were also among the top 10 diseases. Family practitioners, ear-nose-throat specialists, and traditional Chinese medicine physicians were the major health-care providers for Taiwanese adolescents, especially in the middle and late groups. Although noted as the first option for consultation in the early group, the role of pediatricians with regard to adolescent health care declined in importance with age.Nearly 99% of the population in Taiwan is covered under the national health insurance system. The different disease patterns and major health-care providers between Taiwan and other countries are compared.

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.

MicroRNAs are endogenous small non-coding RNAs about 21 nucleotides in length that inhibit the expression of target genes primarily at the post-transcriptional level. The target recognition of microARN is sequence-specific and requires a partial complementarity between the microRNA and target sequences that are present on the mRNA molecules. microRNAs are part of an effector complex, miRISC, containing multiple proteins which can participate to a repression of translation and/or promotes destabilization of the target mRNA. The mechanism of microRNA silencing is not completely understood to date, but it is assumed that it is globally less potent than that of siRNA acting on perfect targets. By using fluorescent proteins expressing reporter plasmids and flow cytometry, we observed an efficient silencing by microRNA which does not require more active complexes than the perfect target silencing and cannot be easily saturated. This suggests that in cells in culture, microRNA silencing works in a catalytic manner leading to mRNA degradation. In addition, our data also indicates that the efficiency of microRNA silencing is variable among cells and can be almost completely abrogated under some conditions contrary to the siRNA silencing which is active in all cells. As we observed that the protein Ago2 is the only member of Ago family that is implicated in the microRNA silencing, it follows that the regulation of microRNA silencing acts after the formation of the core complex (Ago2/small RNA). So the difference between the silencing in the perfect and imperfect mode are not what is usually proposed, but pertain to a level of cellular control, which remains to be deciphered., Les microARN constituent une classe de petits ARN non codants d’une vingtaine de nucléotides, issus de transcrits cellulaires, qui inhibent l’expression de gènes cibles au niveau post-transcriptionnel. Chez les mammifères, bien qu’ils puissent agir sur une cible parfaitement complémentaire (mode parfait), les microARN ont presqu’exclusivement des cibles partiellement complémentaires (mode imparfait). Puisqu’en mode imparfait une coupure endonucléolytique de la cible est impossible, il est généralement proposé que le mode imparfait soit moins efficace que le mode parfait : conduisant à un silencing moins efficace, nécessitant plus de complexes effecteurs (miRISC) et facilement saturable par une augmentation du nombre de cible. Dans ce travail j’ai développé une approche expérimentale reposant sur l’expression de protéines fluorescentes pour mesurer précisément le silencing au niveau de chaque cellule. J’ai fait trois observations inattendues sur l’efficacité de la régulation par les microARN : i) le silencing en mode parfait et imparfait nécessite des quantités similaires de petit ARN, ii) une augmentation, même très importante, de l’expression du gène cible ne lui permet pas d’échapper à la régulation, iii) le silencing n’est pas intrinsèquement plus faible en mode imparfait (qu’en mode parfait) mais n’est pas actif dans toutes les cellules. Si les deux premiers points sont facilement explicables dans le cadre de l’induction de la dégradation de l’ARNm cible sur un mode catalytique via la déadénylation de l’ARNm, le troisième indique l’existence d’une régulation forte du silencing qui est spécifique du mode imparfait. De plus, comme dans les deux modes le silencing dépend principalement du même partenaire, Ago2, cette régulation intervient après l’assemblage du complexe minimal (Ago2/petit ARN). Ainsi, les différences entre les modes parfait et imparfait ne se situent pas au niveau proposé puisque lorsque la cellule est compétente, leurs efficacités sont comparables. Par contre, mes travaux mettent en évidence l’existence d’un contrôle de la régulation en mode imparfait dont la nature reste à préciser.

Background As children represent the future, ensuring that they receive proper health care should be a primary concern of our societies. Epidemiological research underpins the importance of effective child health care strategies, and highlights the need for accurate data collection; such surveys are currently lacking in Taiwan. In our descriptive studies, we compared the differences of the ten most common diseases in the year 2000 and 2009 among Taiwanese children. Methods Data for a total of 174,651 and 142,200 visits under eighteen years old were collected from the National Health Insurance Research Database in year 2000 and 2009. A maximum of three outpatient diagnostic codes (the International Classification of Disease [ICD], ninth revision) could be listed for every visit. Data were categorized according to the principal diagnoses, age and different specialties of physicians. Results Respiratory tract infection was the most common disease (58.21% to 44.77%). Teeth (4.90% to 5.16%) and eye (2.52% to 3.15%) problems were the also in the list of top ten diseases. In year 2009, the rate of allergic rhinitis was 2.87% in 7-18 years old group. Pediatricians were the first option for consultation, followed by ear, nose and throat specialists and family physicians. However, for the school age children group, the role of pediatricians with regards to children's health care showed a decrease in its importance. Conclusions The amount of information relevant to child health care is rapidly expanding. The ten most common diseases of the present analysis may serve as baseline data for future evaluations of the changes of type of diseases among children.

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.

Ornithine decarboxylase (ODC) is the rate-limiting enzyme in polyamine biosynthesis and a target for chemoprevention. Hydroxydibenzoylmethane (HDB), a derivative of dibenzoylmethane of licorice, is a promising chemopreventive agent. In this paper, we investigated whether HDB would inhibit the ODC pathway to enhance apoptosis in human promyelocytic leukemia HL-60 cells. We found ODC enzyme activity was reduced during HDB treatment. Overexpression of ODC in HL-60 parental cells could reduce HDB-induced apoptosis, which leads to loss of mitochondrial membrane potential (Δψ(m)), through lessening intracellular ROS. Furthermore, ODC overexpression protected cytochrome c release and the activation of caspase-3 following HDB treatment. The results demonstrated HDB-induced apoptosis was through a mechanism of down-regulation of ODC and occurred along a ROS-dependent mitochondria-mediated pathway.

Matrix metalloproteinase 9 (MMP-9) has been implicated in airway injury in chronic obstructive pulmonary disease (COPD), lung inflammation, and lung cancer and plays a major role in tumor necrosis factor-α (TNF-α)-stimulated tumor invasion and lung inflammation. MMP-9 activity is promoted by the pro-inflammatory cytokine TNF-α. GMI, cloned from Ganoderma microsporum and purified, is one of the recombinant fungal immunomodulatory proteins. To understand the molecular mechanisms involved in the suppression of TNF-α-mediated tumor invasion and inflammation, GMI modulation of this pathway was investigated in human alveolar epithelial A549 cells in this study. GMI exhibited an inhibitory effect on TNF-α-induced invasion, with GMI treatment and TNF-α exposure presenting the most anti-invasive properties on Boyden chamber assay. GMI reduced TNF-α-induced MMP-9 activities on gelatin zymography assay through inhibition of MMP-9 transcriptional activity. RT-PCR and MMP-9 promoter luciferase analysis revealed that GMI inhibits the transcription of MMP-9 mRNA. Moreover, in vitro and in vivo binding experiments, an electrophoretic mobility shift assay (EMSA), and chromatin immunoprecipitation assay (ChIP) demonstrated that GMI suppresses DNA binding of nuclear factor (NF)-κB transcription factors to MMP-9 promoter. Western blot analysis indicated that GMI blocks the phosphorylation and degradation of IκBα, which in turn leads to suppression of the phosphorylation and nuclear translocation of p65. Thus, overall, our results indicated that GMI mediates antitumor invasion and anti-inflammatory effects through modulation of NF-κB/MMP-9 pathways.

Cellular defenses against allergens and reactive oxygen species (ROS) exposure are critical in the pathogenesis of asthma. CD14 is a receptor for various bacterial products, such as lipopolysaccharides (LPS), and is also a mediator of inflammatory processes. Manganese superoxide dismutase (MnSOD) is an ROS scavenger, and myeloperoxidase (MPO) can convert hydrogen peroxide into hypochlorous acid; thus, they are considered to be involved in inflammatory defense. The authors conducted a case-control study to evaluate the susceptibility to childhood asthma based on CD14, MnSOD, and MPO genes.The CD14 -260, MnSOD -9, and MPO -463 genotypes were identified by polymerase chain reactions for 116 asthmatic children and 232 healthy controls. Questionnaires were administered to obtain demographic characteristics. Allergen testing used common Taiwanese aeroallergens.A higher level of parental education, family history of asthma, incense burning at home, allergen-test positive, and the MnSOD Val-Ala/Ala-Ala genotypes (matched relative risk = 2.0; 95% confidence interval = 1.0-4.2) were significantly associated with childhood asthma. Interactions between CD14, MnSOD, MPO genotypes and allergy status were significantly associated with asthma risk in these children (all p.001). Furthermore, atopic cases with MnSOD Val-Ala/Ala-Ala (log eosinophil 2.66/mm(3), log total serum immunoglobulin E [IgE] 2.48 IU/ml) or Val-Val (log eosinophil 2.61/mm(3), log total serum IgE 2.63 IU/ml) genotypes had elevated eosinophil counts and total serum IgE levels as compared to nonatopic cases with MnSOD Val-Val genotype (log eosinophil 2.27/mm(3), log total serum IgE 1.83 IU/ml).Susceptible MnSOD genotypes might modulate the development of asthma in Taiwanese children.

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.

The burden of asthma is sufficient to warrant its recognition as a high-priority disorder in governmental health strategies in many countries. However, the components of the total health care costs for patients with asthma have not been well studied, and an overall understanding of health care utilization patterns in this population is lacking in Taiwan. We evaluated 95,110 patients aged 18-55 years who were enrolled in the National Health Insurance Research Database from January 1 to December 31, 2002. Health care utilization and costs, including those related to office, outpatient hospital, emergency department, and inpatient hospital visits were compared between patients with and patients without asthma. In 2002, the period prevalence of treated asthma was 1.8%. Patients with asthma used substantially more services than did those without asthma in all categories. The mean costs of hospitalizations for patients with asthma were 2.7-fold higher than those of patients without asthma. Asthma care represented 26% of all health-care services that patients with asthma received, while the remaining 74% were for nonasthma care. Almost one-half of all asthma-related costs were attributable to hospitalizations. These findings may serve as baseline data for future evaluations of changes in health care utilization and expenditures among asthmatic patients.

Hyaluronan or hyaluronic acid (HA) has been used to treat osteoarthritic knees for more than 30 years. Here, we tested the hypothesis that HA with high molecular weight (MW) would have greater effects than HA with low MW on the expression of the plasminogen activator (PA)/plasmin system and gelatinases [matrix metalloproteinase (MMP)-2 and MMP-9] during early development of osteoarthritis (OA). We compared the levels of MMP-2, MMP-9, urokinase-type PA (u-PA), and PA inhibitor-1 (PAI-1) in a series of chondral, meniscal, and synovial cultures of early OA after treatment with or without three different MW HA products (Hyalgan and Artz with low MW, and Synvisc with high MW). Gelatin zymography revealed that three different HA products could decrease the secretion of MMP-2 in all tissue cultures and MMP-9 in meniscal and synovial cultures time-dependently. Enzyme-linked immunosorbent assay showed that Artz and Synvisc had significant inhibition on u-PA and PAI-1 levels after 24 h, but Hyalgan did at 96 h. Compared with Hyalgan and Artz, Synvisc provided the greatest ability to inhibit MMP-2, MMP-9, u-PA, and PAI-1 expression. Our studies clearly demonstrate that the therapeutic effects of using HA to treat early OA may be partially dependant on downregulation of the PA/plasmin system and gelatinases expression, which delay the structural progression of the disease. HA with high MW might have a greater ability than that with low MW to offer effective protection for articular cartilage. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:475–484, 2008

Background: In many countries, the burden of asthma is sufficient to warrant recognition as a high-priority disorder in governmental health strategies. However, the components of the total health-care costs for pediatric patients with asthma have not been well studied, and an overall understanding of health-care utilization patterns in this population is lacking in Taiwan. Methods: A total of 33 461 patients aged 3–17 years who were enrolled in the National Health Insurance Research database from 1 January to 31 December 2002 were evaluated. Health-care utilization and costs, including those related to office, outpatient hospital, emergency department, and inpatient hospital visits were compared between pediatric patients with and without asthma. Results: In 2002, the period prevalence of treated asthma was 6.0%. Pediatric patients with asthma used substantially more services than did those without asthma in all categories. Hospital outpatient visits and overall health-care expenditure for patients with asthma were 2.2-fold higher than those of patients without asthma. Asthma care represented 20% of all health-care services that patients with asthma received, while the remaining 80% were for non-asthma care. Almost three-fourths of all asthma-related costs were attributable to office and hospital outpatient visits; one-fourth was attributable to urgent care and hospitalizations. Conclusions: These findings may serve as baseline data for future evaluation of changes in health-care utilization and expenditure among pediatric patients with asthma.

The relationships between uric acid and chronic disease risk factors such as metabolic syndrome, type 2 diabetes mellitus, and hypertension have been studied in adults. However, whether these relationships exist in adolescents is unknown. We randomly selected 8,005 subjects who were between 10 to 15 years old at baseline. Measurements of uric acid were used to predict the future occurrence of metabolic syndrome, hypertension, and type 2 diabetes. In total, 5,748 adolescents were enrolled and followed for a median of 7.2 years. Using cutoff points of uric acid for males and females (7.3 and 6.2 mg/dl, respectively), a high level of uric acid was either the second or third best predictor for hypertension in both genders (hazard ratio: 2.920 for males, 5.222 for females; p

Although allergic asthma and allergic rhinitis have recently been considered to be a single disease, many questions remain unanswered. Why do some atopic patients develop asthma symptoms and others develop allergic rhinitis symptoms? Which factors play a role in the development of different allergic phenotypes? We hypothesized that angiotensin-converting enzyme (ACE) gene polymorphism might play a role in the development of asthma phenotypes in children with allergic rhinitis. The study sample included 106 children with allergic rhinitis, but no asthma, and 105 age- and gender-matched children with allergic rhinitis and asthma. Subjects of both groups exhibited the same systemic immunologic changes and allergen sensitivities. Controls consisted of 102 healthy children. The ACE genotype was determined by polymerase chain reaction. The serum total immunoglobulin E (IgE) level, allergen-specific IgE sensitivity, and eosinophil count were also measured. The frequencies of the DD genotype were significantly higher in the children with both allergic rhinitis and asthma than in the children with allergic rhinitis but no asthma [p = 0.018; odds ratio (OR) = 3.257; (1.222-8.680)]. Results of this study suggest that ACE gene polymorphism DD genotype might play a role in the development of the asthma phenotype in children with allergic rhinitis.

Urinary tract infection (UTI) is a common clinical disorder in younger infants and children and may result in permanent renal damage. The inflammatory cytokines interleukin (IL)-6 and IL-8 play an important role in response to bacterial infection. This prospective study investigated the association between serum and urine IL-6 and IL-8 levels and acute pyelonephritis confirmed by (99m)Tc-dimercaptosuccinic acid (DMSA) scan. A total of 78 children aged 1-121 months with a diagnosis of first-time febrile UTI were included. The following inflammatory markers were assessed: fever; white blood cells count (WBC); C-reactive protein (CRP); and serum and urine IL-6 and IL-8. The patients were divided into the acute pyelonephritis group (n=42) and the lower UTI group (n=36) according to the results of DMSA scan. Fever, WBC and CRP levels were significantly higher in children with acute pyelonephritis than in those with lower UTI (all p0.001). Significantly, higher initial serum and urine IL-6 and IL-8 levels were found in children with acute pyelonephritis than in those with lower UTI (all p0.001). Serum and urine IL-6 in children with acute pyelonephritis were positively correlated with fever, CRP and leucocyturia. These results indicate that both serum and urine IL-6 and IL-8 levels, particularly IL-6, are useful diagnostic tools for early recognition of acute pyelonephritis in febrile children.

Intrapleural instillation of fibrinolytic agent such as urokinase has been shown to be effective as an adjunctive therapy for children with complicated parapneumonic effusion and empyema. In this study, we described our experience with the use of intrapleural urokinase in the management of complicated parapneumonic effusion in children. We collected 13 patients with a mean age of 50.8 months with parapneumonic pleural effusion or empyema; all were treated with intrapleural urokinase after poor response to appropriate antibiotics and simple tube drainage. We also reviewed another 13 patients with a mean age of 45.8 months from the clinical records of children hospitalized with the same conditions prior to urokinase introduction as a control group. The mean fluid drained during the first 24 hours and the first 72 hours after urokinase instillation were significantly greater than those during 24 hours before instillation, p=0.002 and p0.001, respectively. The total volume of fluid drained was also greater in the urokinase group than that in the control group (p0.001). The mean duration of chest tube drainage was significantly shorter in the urokinase group (8.7 +/- 2.8 days vs. 14.7 +/- 6.1 days, p0.02). The mean length of hospitalization was also significantly shorter in the urokinase group (15.5 +/- 5.3 days vs. 24.4 +/- 6.9 days, p=0.002). All 13 patients were managed successfully with urokinase treatment without further surgical procedures. None of the patients experienced any side effect or adverse event after urokinase instillation. Two patients of the control group finally underwent surgical debridement. In conclusion, the use of intrapleural urokinase treatment in children with complicated parapneumonic effusion is an effective and safe therapy.

Angiotensin-converting enzyme (ACE) play a role in inactivating bradykinin and tachykinins. Bradykinin and tachykinins are potent mediators of inflammatory reaction. An insertion/deletion polymorphism of the ACE gene has been shown to be associated with serum ACE levels. We hypothesized that ACE polymorphism might play a role in allergic rhinitis development.Seventy five children aged 6-13 years with atopic allergic rhinitis and 66 age- and gender-matched healthy children were studied. ACE genotypes were determined by polymerase chain reaction. Serum total immunoglobulin E (IgE) and allergen-specific IgE levels were also measured.The frequencies of the DD and non-DD genotypes, and of the II and non-II genotypes did not differ significantly between healthy children and allergic rhinitis children (chi-squared test, p=1.000 and 0.438, respectively). There was no association of ACE genotype and mean IgE levels in rhinitis children or healthy controls.The results of our study indicate that polymorphism of the ACE gene is unrelated to the development of allergic rhinitis, the duration of allergic rhinitis, serum IgE levels, and allergen-specific IgE in Taiwanese children.

Streptococcus pneumoniae is an uncommon etiological organism in children with hemolytic uremic syndrome (HUS). Patients with S. pneumoniae-associated HUS commonly have a pneumonia or meningitis. Historically, S. pneumoniae-associated HUS usually has a poor clinical outcome. We report 3 pediatric cases of pneumococcal pneumonia-induced HUS. All 3 patients were2 years old, had an empyema complicating pneumococcal pneumonia, and developed renal failure with oliguria and required peritoneal dialysis for a period of 9 to 26 days. All children received several transfusions of unwashed packed red cells and platelets. All of the patients survived. Of the 3 cases, 2 had a normal renal function at discharge, and 1 had a mild renal impairment at 16-month follow-up. Our report suggests S. pneumoniae-associated HUS remains a rare but severe complication of invasive pneumococcal infection in children. It is important for pediatricians to note that children with pneumococcal pneumonia with severe hematologic and renal dysfunction should be investigated for evidence of S. pneumoniae-associated HUS.

Immunotherapy through oral routes is thought to be a valuable therapeutic option for asthma. The clinical and immunologic effects of sublingual immunotherapy (SLIT) in children with asthma caused by mites were evaluated in a double-blind, placebo-controlled study for 6 months. Patients (aged 6-12 yr) with mild-to-moderate asthma, with single sensitization to mite allergen, received either SLIT or placebo with a standardized Dermatophagoides pteronyssinus (D.p.)/D. farinae (D.f.) 50/50 extract. The cumulative dose was around 41824 IR, equivalent to 1.7 mg of D.p. and 3.0 mg of D.f. allergen. Symptom and medication scores were assessed throughout the study. Serum total immunoglobulin (Ig)E, eosinophil count, eosinophil cationic protein, specific IgE, specific IgG4, and skin sensitivity were evaluated before starting the treatment and after the treatment period. Twenty patients completed the study. At the beginning of the treatment, no differences were observed between the groups for symptom and medication scores, skin sensitivity, or immunologic parameters. After 6 months of treatment, there was a significant difference in nighttime asthma symptom scores and specific IgG4 (p < 0.05) in the SLIT group compared with the placebo group. Daytime symptom and medication scores, total IgE, eosinophil count, forced expiratory volume in 1 s, and mean evening peak expiratory flow rate reached significant differences in the SLIT group during the treatment period (p < 0.05). No severe adverse effects were reported. Our results revealed that treatment for 6 months with SLIT is clinically effective in decreasing asthmatic symptoms and medication use in children with mild-to-moderate asthma because of mite sensitivity. The clinical usefulness of this form of immunotherapy and the mechanism underlying its immunologic effects deserve further studies.

Magnetic resonance imaging has recently become a noninvasive and cost-effective diagnostic tool for meniscal pathology in the knee. We report an unusual case of primary synovial chondromatosis for which the clinical diagnosis was medial meniscal tear but magnetic resonance imaging also showed a displaced torn meniscus, causing a so-called "double meniscus sign." The patient was definitely diagnosed and successfully treated with arthroscopy. We discuss the clinical diagnostic and therapeutic challenges, and the possible pathogenesis.

Cord blood IgE and atopic family history have been used as predictors of atopic disease in infants for more than 20 years. In recent years, the value of cord blood IgE in predicting the development of atopic dermatitis has been questioned, while family history of atopy has consistently been regarded as a useful predictor for atopic dermatitis. A birth cohort was followed-up to 6 months of age to record the development of atopic dermatitis and to study its association with cord blood IgE levels and parental history of atopy. The cumulative incidence of atopic dermatitis over the 1st, 3rd and 6th months of life amounted to 5.0%, 8.2% and 14.0%, respectively. When the cutoff value for cord blood IgE was set at 0.5 kU/L, there was a significant association between elevated cord blood IgE level and atopic dermatitis at 1, 3 and 6 months of age; when the cutoff value was set at 0.9 kU/L, the association was only found at 3 months of age. There was a significant association with atopic history of the mother. The effect of maternal atopic history on atopic dermatitis seen only at 1 month was lost by 3 months of age. There was no correlation between paternal history and atopic dermatitis. In our study, the predictive capacity of maternal history and cord blood IgE was not high enough to recommend them as screening factors.

To determine the possible role of the plasminogen activator (PA)/plasmin system in gouty arthritis.We compared the antigenic values of urokinase-type PA (uPA), soluble uPA receptor (suPAR), and PA inhibitor type-1 (PAI-1) and the levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 in 63 synovial fluid (SF) samples from knee joints of 38 patients with gouty arthritis and 20 SF samples from knee joints of 20 patients with osteoarthritis (OA).The increases of uPA, suPAR, and PAI-1 antigenic values in SF were associated with increased levels of latent MMP-9 (pro-MMP-9) (p0.001, p0.001, p0.001, respectively) in gouty arthritis, whereas a correlation was not observed between uPA, suPAR, and PAI-1 antigenic values and MMP-2 levels. Increased uPA, suPAR, and PAI-1 antigenic values in gouty arthritis SF were also correlated to each other (p0.001, p0.001, p0.001). In gouty arthritis SF, no significant relations were observed between uPA and suPAR antigenic values and leukocyte, neutrophil, or monocyte counts, while increased values of PAI-1 corresponded closely with increased leukocyte and neutrophil counts (p = 0.005, p = 0.004). Significantly higher values of the uPA, suPAR, and PAI-1 (p0.001, p0.001, p = 0.012) appeared in SF of gouty arthritis than in SF from patients with OA.These results show a correlation of the PA/plasmin system and MMP-9 in SF from patients with gouty arthritis, resulting in increased PA catalytic activity and contributing to inflammation in gouty arthritis.

Leukotriene receptor antagonists (LTRAs) were recently added to the method of treating allergic rhinitis (AR). However, in children under 6 yr old, there has been no study about its efficacy in treating AR. We aim to compare the clinical efficacy of montelukast, cetirizine and placebo in the treatment of children from 2 to 6 yr old with perennial allergic rhinitis (PAR), to see if there are any significant differences. Sixty children were selected and treated with montelukast, or cetirizine, or placebo once daily. The efficacy of the three agents was compared with the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) and Total Symptom Score (TSS) by diary. In addition, we also examined serum IgE, serum eosinophil cationic protein (ECP), blood eosinophil counts, nasal airway resistance (NAR) and eosinophil percentage in nasal smears. The results revealed that both montelukast and cetirizine were significantly efficacious compared with placebo in NAR, eosinophil percentage in nasal smears, PRQLQ, TSS and all symptom items except nasal itching, throat itching and tearing. For nasal itching, only cetirizine was significantly efficacious. On the other hand, for night sleep quality, montelukast was significantly superior to cetirizine.

Guidelines from the Global Initiative for Asthma (GINA) mention several medications for the treatment of asthma. These medications include oral and inhaled beta-2 agonists, oral and inhaled corticosteroids, xanthines, leukotriene receptor antagonists, and their combinations. In addition to asthma, these drugs are commonly prescribed to treat other respiratory diseases, such as acute bronchitis, chronic cough, lower respiratory infection, or even bronchopneumonia. We analyzed differences in prescribing patterns between pediatric patients with and those without asthma, as coded in the claim records from the National Health Insurance Research Database. Oral beta-2 agonists were the most frequently monotherapy in both groups of patients (52.6-77.6% vs 62.8-84. 8%). Oral beta-2 agonists combined with xanthines or oral corticosteroids combined with an oral beta-2 agonist were the most frequent combination therapies in both groups. Inhaled corticosteroids were used in 3.1-11.0% of patients with asthma; the rate varied by patient age. In conclusion, prescribing patterns were similar in pediatric patients with and those without asthma.

The purpose of this study was to evaluate the relationship between air pollution and asthma exacerbation in children and adults. Pearson analysis was used to establish correlations between air pollutants—sulfur dioxide, nitrogen dioxide, ozone, carbon monoxide, and particles with an aerodynamic diameter of 10 μ m or less (PM 10 )—and ED visits for asthma in 2004. Among children, there were significant positive correlations between nitrogen dioxide ( r = 0.72), carbon monoxide ( r = 0.65), and PM 10 ( r = 0.63) and ED visits for asthma. Among adults, only weakly positive, non significant correlations between all air pollution measures and ED visits for asthma were found. This study suggests that air pollution plays a role in acute exacerbation of asthma in children but not in adults.