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Background World Health Organization recommends countries introducing new drug and short treatment regimen for drug resistant tuberculosis (DR-TB) should develop and implement a system for active pharmacovigilance that allows for detection, reporting and management of adverse events. The aim of the study is to evaluate the frequency and severity of adverse events (AEs) of bedaquiline-containing regimen in a cohort of Chinese patients with multidrug-resistant (MDR)/extensively drug-resistant (XDR)-TB based on active drug safety monitoring (aDSM) system of New Drug Introduction and Protection Program (NDIP). Methods AEs were prospectively collected with demographic, bacteriological, radiological and clinical data from 54 sites throughout China at patient enrollment and during treatment between February, 2018 and December, 2019. This is an interim analysis including patients who are still on treatment and those that have completed treatment. A descriptive analysis was performed on the patients evaluated in the cohort. Results By December 31, 2019, a total of 1162 patients received bedaquiline-containing anti-TB treatment. Overall, 1563 AEs were reported, 66.9% were classified as minor (Grade 1–2) and 33.1% as serious (Grade 3–5). The median duration of bedaquiline treatment was 167.0 [interquartile range (IQR): 75–169] days. 86 (7.4%) patients received 36-week prolonged treatment with bedaquiline. The incidence of AEs and serious AEs was 47.1% and 7.8%, respectively. The most frequently reported AEs were QT prolongation (24.7%) and hepatotoxicity (16.4%). There were 14 (1.2%) AEs leading to death. Out of patients with available corrected QT interval by Fridericia's formula (QTcF) data, 3.1% (32/1044) experienced a post-baseline QTcF ≥ 500 ms, and 15.7% (132/839) had at least one change of QTcF ≥ 60 ms from baseline. 49 (4.2%) patients had QT prolonged AEs leading to bedaquiline withdrawal. One hundred and ninety patients reported 361 AEs with hepatotoxicity ranking the second with high occurrence. Thirty-four patients reported 43 AEs of hepatic injury referred to bedaquiline, much lower than that referred to protionamide, pyrazinamide and para-aminosalicylic acid individually. Conclusions Bedaquiline was generally well-tolerated with few safety concerns in this clinical patient population without any new safety signal identified. The mortality rate was generally low. These data inform significant positive effect to support the WHO recent recommendations for the wide use of bedaquiline.

Background Patients with heterotaxy syndrome (HS), commonly associated with hyposplenism and complex congenital heart disease (CCHD), require multiple-stage single ventricle type operation for long-term survival. Although a higher risk of community-acquired sepsis and mortality rate was reported in CCHD with HS compared to those without HS, whether the risk of postoperative severe bacterial infection (SBI) is higher in patients with HS remains unknown. Method All patients with CCHD (with and without HS) born between 2001 and 2013 who received cardiac surgery between 2001 and 2018 were enrolled. We analyzed the epidemiology and risk of postoperative SBI in this CCHD cohort. Result In total, 101 patients of CCHD with HS and 164 patients without HS were enrolled. The mean postoperative nosocomial SBI rate was 0.73/100 patient-days in patients with HS and 0.56/100 patient-days in patients without HS (P = 0.13). Multivariate Cox regression analysis demonstrated that the most critical risk factor for postoperative SBI was postoperative intubation >14 days. Preoperative risk factors, including a nonstandard surgical procedure and multiple surgeries, but not HS, were associated with an increased risk of postoperative nosocomial SBI. The pathogens of infection were also similar between these 2 groups. Conclusion Although commonly associated with hyposplenism, patients with HS have similar postoperative SBI risk and pathogens as those with CCHD alone.

Ulcerative colitis (UC) is a chronic, nonspecific inflammatory bowel disease (IBD) characterized by complicated and relapsing inflammation in the gastrointestinal tract. SM934 is a water-soluble artemisinin analogue that shows anti-inflammatory and immuno-regulatory effects. In this study, we investigated the effects of SM934 on UC both in vivo and in vitro. A mouse model of colitis was established in mice by oral administration of 5% dextran sulfate sodium (DSS). SM934 (3, 10 mg/kg per day, ig) was administered to the mice for 10 days. After the mice were sacrificed, colons, spleens and mesenteric lymph nodes (MLNs) were collected for analyses. We showed that SM934 administration restored DSS-induced body weight loss, colon shortening, injury and inflammation scores. Furthermore, SM934 administration significantly decreased the disease activity index (DAI), histopathological scores, and myeloperoxidase (MPO) activities in colonic tissues. Moreover, SM934 administration dose-dependently decreased the mRNA and protein levels of DSS-induced pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α), and the percentage of macrophages and neutrophils in colon tissues. The effects of SM934 on LPS-stimulated RAW 264.7 cells and THP-1-derived macrophages were examined in vitro. Treatment with SM934 (0.8, 8, 80 μmol/L) dose-dependently decreased the production of pro-inflammatory mediators in LPS-stimulated RAW264.7 cells and THP-1-derived macrophages via inhibiting activation of the NF-κB signaling. Our results reveal the protective effects of SM934 on DSS-induced colitis can be attributed to its suppressing effects on neutrophils and macrophages and its inhibitory role in the NF-κB signaling, suggests that SM934 might be a potential effective drug for ulcerative colitis.

Patients with heterotaxy syndrome, commonly associated with complex congenital heart disease (CHD), exhibit a higher risk of severe bacterial infection (SBI). We sought to define the change of a novel immunologic marker, the immunoglobulin M (IgM) memory B-cell percentage, and its association with SBI. We enrolled 46 (M/F 29/17) heterotaxy syndrome patients (42 right atrial isomerism (RAI) and 4 left atrial isomerism (LAI)) aged > 1 y during the period 2010–2012 in a tertiary care center. We analyzed IgM+CD27+ memory B-cell percentages. Patients with simple and complex CHD served as controls. The mean IgM memory B-cell percentages were the lowest in the heterotaxy syndrome group, compared with those in complex and simple CHD groups (1.8 ± 2.1 vs. 3.9 ± 3.2 vs. 5.1 ± 4.7, P < 0.001). In the heterotaxy syndrome group, 41.3% had low IgM memory B-cell percentages (

This study aims to explore the safety and efficacy of intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) in elderly (≥80 years old) acute ischemic stroke (AIS) patients. The clinical data of patients who were treated in Tianjin Huanhu Hospital from June 2012 to November 2013 were retrospectively analyzed; among them, 404 patients had received IVT with rt-PA and 200 patients had not received IVT. Among ≥80-year-old patients, 204 had received IVT and 200 had not. And the 404 patients who had received IVT were divided into two subgroups: elderly (≥80 years of age; n = 204) and controls (

The use of intravenous thrombolytic therapy (ITT) in acute ischemic stroke (AIS) patients is still debated in China. We present the analysis of clinico-demographic retrospective data of 646 AIS patients that were treated by alteplase ITT at our hospital. The data collected included age, gender, education, income, drug use before disease onset, and awareness of stroke/ITT. The risk factors studied were hypertension, diabetes, hyperlipidemia, atrial fibrillation, coronary heart disease, cerebral infarction, transient ischemic attack, valvular heart disease, thyroid disease, migraine, asymptomatic carotid stenosis, family history of stroke, hyperhomocysteinemia, smoking, drinking, and gingivitis. Pre-ITT patient data included blood pressure and time from onset to hospital. Post-ITT patient data included National Institutes of Health Stroke Scale (NIHSS) scores, clinical outcome, revascularization, hemorrhage, healing rate, and 90-day mortality. Hospital management information included monthly ITT cases, discharges, bed turnaround times, length of hospital stay, bed utilization, drug ratio, massive cerebral infarction decompressive craniectomy, and social impact. Prognosis evaluation was based on post-ITT NIHSS and modified Rankin Scale (mRS) scores. We found that ITT success rate was 75.85 %, with a bleeding rate of 1.55 % and a 90-day mortality rate of 2.01 %. Overall, the data suggest that the ITT therapy was highly successful in AIS patients treated at our hospital.

Background/purpose Kawasaki disease (KD) is a disease of unknown cause and the causative agent is most likely to be infectious in nature. To investigate the household transmission pattern of infectious illness and etiology, we thus initiated a prospective case and household study. Methods We enrolled KD cases and their household members from February 2004 to September 2008. The KD cases and their household members accepted questionnaire-based interviews of the contact history, signs of infection, and symptoms to check whether clusters of infectious illness occurred. Results A total of 142 KD cases and 561 household members were enrolled. Among the 142 KD cases, 136 cases (96%) were typical KD, and six (4%) were atypical KD. Of the 561 household members, 17% were siblings, 46% were parents, 18% were grandparents, and the others were cousins or babysitters. Prior to the onset of their KD illness, 66% (94/142) KD cases had contact with ill household members. On the same day of the onset of KD cases' illness, 4% (6/142) KD cases had household members with illness. After KD cases' disease onset, 70% (100/142) KD cases had at least one other family member with illness. Overall, 61% (343/561) of all the household members had acute infectious illness during KD cases' acute stage, and 92% (130/142) of the families had clusters of infectious illness. Conclusion A total of 66% KD cases had positive contact with ill household members prior to their disease onset and 92% of families had clusters of infectious illness, so KD is strongly associated with infections.

BACKGROUND The epidemiology of infective endocarditis (IE) changes with the medical advances. This study aimed to evaluate the trends in a pediatric cohort. METHODS From hospital database (1983-2011), patients

To investigate the immunomodulating activity of astragalosides, the active compounds from a traditional tonic herb Astragalus membranaceus Bge, and to explore the molecular mechanisms underlying the actions, focusing on CD45 protein tyrosine phosphatase (CD45 PTPase), which plays a critical role in T lymphocyte activation.Primary splenocytes and T cells were prepared from mice. CD45 PTPase activity was assessed using a colorimetric assay. Cell proliferation was measured using a [(3)H]-thymidine incorporation assay. Cytokine proteins and mRNAs were examined with ELISA and RT-PCR, respectively. Activation markers, including CD25 and CD69, were analyzed using flow cytometry. Activation of LCK (Tyr505) was detected using Western blot analysis. Mice were injected with the immunosuppressant cyclophosphamide (CTX, 80 mg/kg), and administered astragaloside II (50 mg/kg).Astragaloside I, II, III, and IV concentration-dependently increased the CD45-mediated of pNPP/OMFP hydrolysis with the EC50 values ranged from 3.33 to 10.42 μg/mL. Astragaloside II (10 and 30 nmol/L) significantly enhanced the proliferation of primary splenocytes induced by ConA, alloantigen or anti-CD3. Astragaloside II (30 nmol/L) significantly increased IL-2 and IFN-γ secretion, upregulated the mRNA levels of IFN-γ and T-bet in primary splenocytes, and promoted CD25 and CD69 expression on primary CD4(+) T cells upon TCR stimulation. Furthermore, astragaloside II (100 nmol/L) promoted CD45-mediated dephosphorylation of LCK (Tyr505) in primary T cells, which could be blocked by a specific CD45 PTPase inhibitor. In CTX-induced immunosuppressed mice, oral administration of astragaloside II restored the proliferation of splenic T cells and the production of IFN-γ and IL-2. However, astragaloside II had no apparent effects on B cell proliferation.Astragaloside II enhances T cell activation by regulating the activity of CD45 PTPase, which may explain why Astragalus membranaceus Bge is used as a tonic herb in treating immunosuppressive diseases.

Contact tracing and seroepidemiologic studies were done after a premature baby contracted pertussis in a children's hospital. No infection source was confirmed. Four (3.5%) healthcare providers were positive for anti-pertussis IgM, while only 23% (26/113) were positive for IgG in a following survey. Pertussis vaccination for healthcare providers is needed.

Background Influenza virus infection is a major threat to human health. Small interfering RNA (siRNA) is a promising approach for the prevention and treatment of viral infections. In this study, we constructed a series of DNA vector-based short hairpin RNAs (shRNAs) that target various genes of the influenza A virus using the polymerase III U6-RNA promoter to prevent influenza virus infection in vitro and in a mouse model. Results Three sets of DNA vector-based shRNA, two targeting genes encoding the polymerase acidic protein (PA) and one targeting polymerase basic protein 2 (PB2), efficiently inhibited the replication of influenza virus A/WSN/33(H1N1) in vitro. We also successfully prevented influenza virus A/WSN/33(H1N1) infection in a C57BL/6 mouse model by intratracheal delivery of anti-PB2 shRNA. Conclusions Our findings suggest that the PB2-targeting shRNA plasmid showed potential for use as an RNAi-based therapeutic for influenza virus infection.

BACKGROUND Infection is a major complication in pediatric patients with acute lymphoblastic leukemia during chemotherapy. In this study, the infection characteristics were determined and risk factors analyzed based on the Taiwan Pediatric Oncology Group (TPOG) acute lymphoblastic leukemia (ALL) protocol. PROCEDURE We retrospectively reviewed fever events during chemotherapy in 252 patients treated during two consecutive clinical trials at a single institution between 1997 and 2012. Patients were classified as standard, high, and very high risk by treatment regimen according to the TPOG definitions. We analyzed the characteristics and risk factors for infection. RESULTS Fever occurred in 219 patients (86.9%) with a mean of 2.74 episodes per person. The fever events comprised 64% febrile neutropenia, 39% clinically documented infections, and 44% microbiologically documented infections. The microbiologically documented infections were mostly noted during the induction phase and increased in very high risk patients (89 vs. 24% and 46% in standard-risk and high-risk patients, respectively). Younger age and higher risk (high-risk and very high risk groups) were risk factors for fever and microbiologic and bloodstream infections. Female gender and obesity were additive risk factors for urinary tract infection (odds ratios = 3.52 and 3.24, P < 0.001 and P = 0.004, respectively). CONCLUSIONS Infections developed primarily during the induction phase, for which younger age and higher risk by treatment regimen were risk factors. Female gender and obesity were additive risk factors for urinary tract infection.

BackgroundPneumococcal vaccines, including pneumococcal polysaccharide vaccine (PPV) and pneumococcal conjugated vaccine (PCV), are crucial in preventing invasive pneumococcal diseases. We analyzed the pneumococcal vaccination rate, efficacy, and durability in patients with heterotaxy.MethodsAll patients with heterotaxy and CCHD who were followed up at our institution between 2010 and 2015 were included. Pneumococcal vaccine status and geometric mean concentration (GMC) of serotypes 6B, 14, 19F, and 23F were analyzed. Splenic function was considered abnormal when the percentage of IgM memory B cell was less than 1%.ResultsThe GMCs of the four serotypes did not differ significantly between patients with heterotaxy and those with CCHD; the GMCs were also not affected by abnormal splenic function. Most patients had GMCs0.35 μg/ml (protection level) 4-5 years after either PPV or PCV injection; however, it may decay gradually in some serotypes. In addition, 21.4% of 42 patients with heterotaxy did not receive pneumococcal vaccine, and none completely adhered to the vaccine guidelines.ConclusionsVaccine efficacy was acceptable, even in patients with abnormal splenic function. In some patients, the durability of PPV and PCV decreased with time, highlighting the importance of booster doses. Vaccination rate in patients with heterotaxy is unsatisfactory.

Background/PurposeData on hospitalized novel influenza A (H1N1) infected children are limited and urgently in demand. We conducted a clinical study to identify clinical features and risk factors associated with severe novel H1N1 infections of children in Taiwan.MethodsFrom July 24, 2009 to December 4, 2009, data from 61 hospitalized children infected with 2009 novel H1N1 were collected. Demographics, underlying medical conditions, clinical data, receipt of antiviral therapy, need for intensive care and outcome were analyzed to identify clinical features and risk factors of severe infections.ResultsOf the 61 inpatients, the male to female ratio was 41 to 20 and the most common age group was between 6 and 12 years (36%). Almost all (98%) patients had fever, 53 (87%) patients received oseltamivir treatment and 51% of them received oseltamivir within 48 hours. Fourteen (23%) needed intensive care and 3 died. Obesity (a Body Mass Index ≥ 25 kg/m2 in children ≥ 2 years of age, or a body weight ≥ the 95th percentile in children 3 mg/dL, pleural effusion, and delayed antiviral therapy were significantly associated with the need for intensive care and/or death.ConclusionObesity, dyspnea, CRP > 3 mg/dL, pleural effusion, and delayed antiviral therapy are significantly associated with severe novel H1N1 infections in children.

During August–November 2009, to investigate disease transmission within households in Taiwan, we recruited 87 pandemic (H1N1) 2009 patients and their household members. Overall, pandemic (H1N1) 2009 virus was transmitted to 60 (27%) of 223 household contacts. Transmission was 4× higher to children than to adults (61% vs. 15%; p

Background/PurposeRespiratory Syncytial Virus (RSV) is the leading cause of hospitalization in young children. The population-based burden of RSV hospitalization and the effect of potential risk factors on the severity of illness were evaluated in Taiwanese children.MethodsWe analyzed the annual population-based incidence, underlying diseases and characteristics of hospitalizations due to RSV in Taiwanese children under 5 years of age from 2004 to 2007 by using Taiwan's National Health Insurance database.ResultsA total of 11,081 children with RSV-associated hospitalization were studied. Average annual population-based hospitalization incidence was 1,077 and 232 per 100,000 children-year in children under 6 months and under 5 years of age, respectively. The peak incidence occurred between 1 and 2 months of age. The male-to-female incidence risk ratio was 1.4:1 (p < 0.001). There was a significant seasonal distribution with consistent peaks in the spring and autumn every year (p < 0.001). A total of 373 patients (3.3%) had repeated RSV infection. The 943 children (8.5%) with underlying diseases were older (p = 0.001), required longer intensive care unit (ICU) stays (p < 0.001), had a higher rate of endotracheal intubation (p < 0.05), and incurred higher medical costs (p < 0.001). A total of 888 patients (8%) required ICU care. Younger age (p < 0.001), prematurity (p < 0.001), cerebral palsy (p < 0.001) and congenital heart disease (p < 0.001) were independent predictors of requiring ICU care.ConclusionRSV infection occurs biennially with peaks in spring and fall in Taiwan. Patients with underlying diseases need longer hospital and ICU stays and incur higher medical costs. Younger age, prematurity, congenital heart disease and cerebral palsy are predictors of ICU care.

The 2009 pandemic influenza A (H1N1) has caused significant morbidity and mortality around the world. Safety and immunogenicity studies of 2009 pandemic influenza A (H1N1) virus in children and adolescents are limited. In this prospective, open-label study, 2 doses of a monovalent, unadjuvanted, inactivated, split-virus 2009 pandemic influenza virus A (H1N1) vaccine (AdimFlu-S) were administered to 183 healthy children and adolescents aged 1-17 years. Adverse reactions were assessed, and hemagglutination inhibition antibody titers were determined. Three weeks after the first dose, 36.2% of children aged 1-2 years, 52.5% of children aged 3-5 years, 56.7% of children aged 6-9 years, and 90.3% of adolescents aged 10-17 years generated protective antibodies. A second vaccination given 3 weeks later induced protective antibodies in 89.4% of all age groups. No severe adverse effects were found 6 weeks after vaccination.

In the present study, we investigated the immunosuppressive effects and underlying mechanisms of beta-aminoarteether maleate (SM934), a derivative of artemisinin, against T cell activation in vitro and in vivo. In vitro, SM934 significantly inhibited the proliferation of splenocytes induced by concanavalin A (Con A), lipopolysaccharide (LPS), mixed lymphocyte reaction (MLR), and anti-CD3 plus anti-CD28 (anti-CD3/28). SM934 significantly inhibited interferon (IFN)-gamma production and CD4(+) T cell division stimulated by anti-CD3/28. SM934 also promoted apoptosis of CD69(+) population in CD4(+) T cells stimulated by anti-CD3/28. Furthermore, SM934 inhibited interleukin (IL)-2 mediated proliferation and survival through blocking Akt phosphorylation in activated T cells. In ovalbumin (OVA)-immunized mice, oral administration of SM934 suppressed OVA-specific T cell proliferation and IFN-gamma production. SM934 treatment also significantly inhibited the sheep red blood cell (SRBC)-induced delayed type hypersensitivity (DTH) reactions in mice. Taken together, SM934 showed potent immunosuppressive activities in vitro and in vivo. Our results demonstrated that SM934 might be a potential therapeutic agent for immune-related diseases.

Background/Purpose: Meningococcal disease, including meningitis and sepsis, usually follows an invasive infection by Neisseria meningitidis, and is a major cause of death and morbidity worldwide. Currently available meningococcal vaccines that consist of pure capsular polysaccharides (serogroups A, C, W-135 and Y) are generally safe and efficacious in adults and children aged ＞2 years. The purpose of this study was to evaluate the immunogenicity, safety and reactogenicity of a single dose of GlaxoSmithKline Biologicals' Mencevax(superscript TM) ACWY vaccine in healthy Taiwanese subjects aged 2-30 years. Methods: This open, single center, Phase Ⅲ study was conducted in Taiwan. A single dose of the Mencevax(superscript TM) ACWY vaccine was administered to subjects aged 2-30 years. Immunogenicity and safety of the vaccine were evaluated after vaccination. Results: The immunogenicity results obtained 1 month after vaccination with Mencevax(superscript TM) ACWY vaccine indicated that the vaccine elicited a good immune response in vaccinees aged 2-30 years. This was both in terms of functional activity directed against meningococcal polysaccharide (A, C, W-135 and Y) as measured by serum bactericidal assay (＞93% activity against all serogroups), and specific IgG concentrations measured by ELISA (＞96% seropositivity to all serogroups). Conclusion: The tetravalent polysaccharide Mencevax(superscript TM) ACWY meningococcal vaccine was well tolerated and immunogenic in subjects aged 2-30 years in Taiwan.

Background Few studies have investigated the epidemiology and disease burden of childhood pneumonia in Taiwan, a middle-income country. Methods Using Taiwan's National Health Insurance database, we analyzed the annual population-based incidence and mortality rate of hospitalizations due to pneumonia in children under 18 years old from 1997 to 2004 in Taiwan. Results The average annual incidence of hospitalized pneumonia was 1,240 episodes per 100,000 children in those below 18 years old. For children under 5 years old and for infants, the incidence was 3,965 and 4,984 out of 100,000, respectively. Boys were more likely to be affected than girls (male to female risk ratio 1.27, P

Background/Purpose: A prospective study was initiated to study astroviral infections in Taiwan. Methods: A total of 415 stool samples were collected and assayed for astrovirus antigen using an enzyme immunoassay. Results: Twelve (2.9%) stool samples from 12 patients were positive for astrovirus antigen. Most patients (8/12) had watery diarrhea which lasted for 2-6 days. The majority of patients recovered without specific treatment, except for two patients who were treated with antibiotics for possible bacterial infections. One patient developed chronic diarrhea and two episodes were nosocomially acquired. A clustering in the autumn and winter, with a peak in December (5/12), was noted. Growth on Caco-2 cells was performed for four specimens with positive astroviral RT-PCR results, and a characteristic cytopathic effect was observed after 4 days. Astroviral RNA was detected in six stool samples using RT-PCR. Five of six strains were serotype 1 and one strain was serotype 3. Sequence homology among the six strains was between 80.5% and 100%. A higher degree of homology (89.9-100%) was noted in the five strains of serotype 1. A phylogenetic study demonstrated two clusters in our strains and Oxford reference strain types 1 and 2. Conclusion: Our study results provide further information about the prevalence and span of clinical spectra associated with astroviral infections in Taiwan. The current study showed that infection with astroviruses may be an important cause of gastroenteritis, as well as respiratory symptoms, in infants and children in Taipei. [J Formos Med Assoc 2008; 107(4):295-303]

(5R)-5-hydroxytriptolide (LLDT-8) displayed anti-arthritis and anti-allogenic transplantation rejection activities in our previous studies. Here, we aim to further clarify the effect of LLDT-8 on the pro-inflammatory cytokine IFN-gamma.T cells were activated with anti-CD3 antibody or concanavalin A (ConA). The expression of cell surface molecules was detected with flow cytometry. Cells were labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE) to test cell division. IFN-gamma production was determined by enzyme-linked immunosorbent assay. Cell proliferation was evaluated by [3H]-thymidine uptake. Mice were immunized with ovalbumin to assess the in vivo immune response. RT-PCR and Real-time PCR were applied to determine the mRNA expression. The protein phosphorylation levels were detected by Western immunoblot assay.LLDT-8 at 100 nmol/L did not change the CD25, CD69, and CD154 expressions in anti-CD3-stimulated T cells. LLDT-8 markedly blocked the cell division of CD4 and CD8 T cells after ConA stimulation. LLDT-8 inhibited T cell-derived IFN-gamma production. Moreover, LLDT-8 suppressed the ovalbumin-specific T cell proliferation and IFN-gamma generation. In anti-CD3-activated T cells, LLDT-8 abrogated the mRNA expression of signal transducer and activator of transcription1 (STAT1), T-box transcription factor, IL-12 receptor beta2, STAT4, and interferon regulatory factor 1 in the IFN-gamma expression pathway. Western blot analysis showed that LLDT-8 blocked the phosphorylation levels of extracellular signal-regulated kinase, stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase in anti-CD3 plus anti-CD28-activated T cells. In addition, LLDT-8 reduced the transcripts of macrophage inflammatory protein (Mip)-1alpha, Mip-1beta, regulated upon activation normally T-cell expressed and secreted, inducible protein-10, IFN-inducible T cell a chemoattractant, and monokine induced by IFN-gamma in IFN-gamma-stimulated murine macrophage cell line Raw 264.7 cells.LLDT-8 was a potential inhibitor for IFN-gamma-associated signaling.

Peak systolic mitral annular velocities correlate with left ventricular ejection fraction (EF) regardless of mitral regurgitation severity. Peak systolic tricuspid annular velocity (RV-Sm) and tricuspid annular plane systolic excursion (TAPSE) are used to assess right ventricular (RV) EF (RVEF). We investigated whether tricuspid regurgitation (TR) affects the relationship among RV-Sm, TAPSE, and RVEF.Patients (n = 625) underwent echocardiography and Doppler tissue studies. Left ventricular EF and RVEF were estimated by Simpson's rule. Because of confounding, we excluded patients with diseases that influence mitral annular motion or left ventricular function. We finally enrolled 225 patients: 125 with mild TR, 50 with moderate TR, and 50 with severe TR. Forty study patients (20 with mild TR, 10 with moderate TR, and 10 with severe TR) received radionuclide ventriculography.The RVEF estimated by Simpson's method correlated strongly to that estimated by the radionuclide method (r = 0.793, r2 = 0.629, P.0001). With mild or moderate TR, RV-Sm correlated well to RVEF (mild TR group: r = 0.765, r2 = 0.59, P.0001; moderate TR group: r = 0.756, r2 = 0.57, P.0001). RV-Sm had no significant correlation to RVEF in patients with severe TR (r = 0.212, r2 = 0.05, P = .167). Over a range of TR severities, the relationship between TAPSE and RVEF showed a similar trend to that between RV-Sm and RVEF.Severe TR has a significant impact on the relationship between RV-Sm and RVEF and between TAPSE and RVEF. TAPSE and RV-Sm in patients with severe TR show poor correlation to RVEF. When applying Doppler tissue method or TAPSE to assess RV function, severe TR is a significantly confounding factor.

(5R)-5-hydroxytriptolide (LLDT-8) exhibits strong immunosuppressive activities in vitro and in vivo. Here, we investigated the effects of LLDT-8 on concanavalin A-induced hepatitis. Liver damage was evaluated by serum alanine transaminase (ALT) level and liver histology. The effects of LLDT-8 were determined by measurement of serum cytokines, lymphocyte proliferation assay, flow cytometry analysis of splenic T cell percentage and apoptosis, reverse-transcription polymerase chain reaction (RT-PCR) analysis for gene transcriptions. In LLDT-8-treated mice, serum ALT level and histological damage were markedly attenuated. The beneficial effect of LLDT-8 was closely associated with (i) reduction of serum tumor necrosis factor-alpha, interferon-gamma (IFN-gamma), interleukin-2, interleukin-12, and interleukin-6 levels; (ii) elimination of activated T cells by increasing proapoptotic genes signal transducer and activator of transcription 1 (STAT1) and interferon regulatory factor-1 (IRF-1) expression in spleens; (iii) blockade of mRNA expressions for chemokines (monokine induced by IFN-gamma, Mig; IFN-gamma-inducible protein-10, IP-10; IFN-inducible T cell-alpha chemoattractant, I-TAC), vascular adhesion molecule-1 (VCAM-1), and chemokine receptors (C-C chemokine receptor 1, CCR1; C-C chemokine receptor 5, CCR5; C-X-C chemokine receptor 3, CXCR3) in livers. These results suggested the therapeutic potential of LLDT-8 in IFN-gamma/STAT1/IRF-1 signaling- and inflammatory cytokines-mediated immune disorders.

Background/Purpose: Pneumococcal infection causes high morbidity and mortality in children. Prevention of pneumococcal diseases by effective vaccination is an urgent need. This study evaluated the safety and immunogenicity of heptavalent pneumococcal conjugate (7VPnC) vaccine (serotypes 4, 6B, 9V, 14, 18C, 19F, 23F) booster dose administered at 15-20 months of age in Taiwanese toddlers. Methods: Fifty-eight healthy Taiwanese toddlers who were primed with three doses of the 7VPnC vaccine in infancy received a booster dose in an open-label, noncomparative trial. Routine oral polio vaccine and diphtheria toxoid, tetanus toxoid, and pertussis vaccine were administered concomitantly. Surveillance for safety was conducted after vaccination. Antibody concentration to each of the seven pneumococcal serotypes was measured before and 1 month after the booster dose. Results: Mild to moderate local reactions were common (45-50%). Fever, fussiness, restlessness, and loss of appetite were the most frequent systemic reactions (31-50%). Before the booster dose of vaccine, 68% (for serotype 18C) to 100% (for serotype 14) of subjects had antibody concentrations ≥0.2μg/mL to different pneumococcal serotypes. After the booster dose, the geometric mean concentration of IgG increased significantly (p＜0.001) for all seven serotypes indicating the induction of immunologic memories. Ninety-eight percent of the toddlers had antibody concentration ≥0.2μg/mL against all serotypes after the booster. Conclusion: The 7VPnC vaccine containing the prevalent serotypes in Taiwan is safe and effective in boosting immunity against pneumococcal disease in Taiwanese children.

To explore the effectiveness and safety of intravenous thrombolysis (IVT) using recombinant tissue plasminogen activator in treating acute ischemic stroke patients with concomitant intracranial aneurysms (IA) of ≤3 mm. Clinical data of patients who were treated in Tianjin Huanhu Hospital from June 2012 to September 2013 were retrospectively analyzed. Patients were divided into the following groups: (a) IVT group, in which there were 30 acute ischemic stroke patients with IA of ≤3 mm and 30 patients without aneurysms; and (b) IA group, in which there were 30 patients who did not receive IVT and 30 patients who received IVT. The incidence of intracranial hemorrhage, case-fatality, and good outcome rate was compared within these two groups. Inside the IVT group, the incidence of systematic intracranial hemorrhage and case-fatality showed no significant differences between patients with concomitant IA and those without IA. The 3-month good outcome rate was also not significantly different (24 [80.0 %] vs. 27 [90 %]; P = 0.278). In IA group, patients who had received IVT showed significantly superior good outcome rate than those who had not received IVT (24 [80.0 %] vs. 16 [53.3 %]; P = 0.028).The incidence of intracranial hemorrhage and case-fatality rate were not significantly different between these two subgroups as well. IVT is effective and safe method for the treatment of acute ischemic stroke patients with saccular IA of ≤3 mm.

We previously reported that SM934, a water-soluble artemisinin derivative, was a viable treatment in murine lupus models. In the current study, we further investigated the therapeutic effects of a modified dosage regimen of SM934 on lupus-prone MRL/lpr mice and explored its effects on B cell responses, a central pathogenic event in systemic lupus erythematosus (SLE). When orally administered twice-daily, SM934 significantly prolonged the life-span of MRL/lpr mice, ameliorated the lymphadenopathy symptoms and decreased the levels of serum anti-nuclear antibodies (ANAs) and of the pathogenic cytokines IL-6, IL-10 and IL-21. Furthermore, SM934 treatment restored the B-cell compartment in the spleen of MRL/lpr mice by increasing quiescent B cell numbers, maintaining germinal center B-cell numbers, decreasing activated B cell numbers and reducing plasma cell (PC) numbers. Ex vivo, SM934 suppressed the Toll-like receptor (TLR)-triggered activation and proliferation of B cells, as well as antibody secretion. Moreover, the present study demonstrated that SM934 interfered with the B-cell intrinsic pathway by downregulating TLR7/9 mRNA expression, MyD88 protein expression and NF-κB phosphorylation. In human peripheral blood mononuclear cells (PBMCs), consistent with the results in MRL/lpr mice, SM934 inhibited TLR-associated B-cell activation and PC differentiation. In conclusion, a twice daily dosing regimen of SM934 had therapeutic effects on lupus-prone MRL/lpr mice by suppressing B cell activation and plasma cell formation.

To examine the therapeutic effects and underlying mechanisms of DZ2002, a reversible S-adenosyl-L-homocysteine hydrolase (SAHH) inhibitor, on lupus-prone female NZB×NZW F1 (NZB/W F1) mice.Female NZB/W F1 mice were treated orally with DZ2002 (0.5 mg·kg(-1)·d(-1)) for 11 weeks, and the proteinuria level and body weight were monitored. After the mice ware euthanized, serum biochemical parameters and renal damage were determined. Splenocytes of NZB/W F1 mice were isolated for ex vivo study. Toll-like receptor (TLR)-stimulated human peripheral blood mononuclear cells (PBMCs) or murine bone marrow-derived dendritic cells (BMDCs) were used for in vitro study.Treatment of the mice with DZ2002 significantly attenuated the progression of glomerulonephritis and improved the overall health. The improvement was accompanied by decreased levels of nephritogenic anti-dsDNA IgG2a and IgG3 antibodies, serum IL-17, IL-23p19 and TGF-β. In ex vivo studies, treatment of the mice with DZ2002 suppressed the development of pathogenic Th17 cells, significantly decreased IL-17, TGF-β, IL-6, and IL-23p19 production and impeded activation of the STAT3 protein and JNK/NF-κB signaling in splenocytes. DZ2002 (500 μmol/L) significantly suppressed TLR agonists-stimulated up-regulation in IL-6, IL-12p40, TNF-α, and IgG and IgM secretion as well as in HLA-DR and CD40 expression of dendritic cells among human PBMCs in vitro. DZ2002 (100 μmol/L) also significantly suppressed TLR agonists-stimulated up-regulation in IL-6 and IL-23p19 production in murine BMDCs, and prevented Th17 differentiation and suppressed IL-17 secretion by the T cells in a BMDC-T cell co-culture system.DZ2002 effectively ameliorates lupus syndrome in NZB/W F1 mice by regulating TLR signaling-mediated antigen presenting cell (APC) responses.

Background Tranexamic acid (TA) is a traditional plasmin inhibitor, and its role in the renovation of damaged skin has become the topic of a lot of research. The aim of this study is to determine whether TA could repair the skin barrier by means of tight intercellular junctions. Methods Two kinds of damaged skin models were set up and subjected to repeated application of sodium lauryl sulfate and irradiation of ultraviolet B. Through bioengineering technology and immunohistochemistry tests, TA-induced changes in skin were detected. Results After 1, 3, 7, and 14 days of application, TA can significantly accelerate barrier recovery and decrease the melanin index values of ultraviolet B irritation skin. The mean optic density of occludin from TA treatment is higher than from self-repair. Conclusion These experiments suggest that TA can accelerate skin barrier recovery and upregulate occludin induced by physicochemical damages of human skin, but it is advisable to perform more research on the upregulation of occludin in molecular mechanism in the future.

Objective Drug use evaluation (DUE) criteria were established to assess the rational use of antibiotic prophylaxis (RUAP) in Type I incision operations (TOIO) during peri-operation period and to enhance pharmacists' responsibilities for antibiotic stewardship. Methods The criteria were set with a threshold based on a literature review and discussions with multidisciplinary experts. Patients who received TOIO from July 2008 to June 2012 were enrolled in the study. The percentage of prescriptions adhering to all items of criteria was 10% at baseline. Results According to DUEs and interviews by pharmacists, the percentages of prescriptions adhering to all items of criteria of DUE-1, DUE-3, DUE-5, and DUE-8 were 13.3, 20.0, 50.0 and 66.7%, respectively. The study showed that the most common inappropriate therapies were no indications for prophylaxis antibiotic use and inappropriate choices of antibiotics. Pharmacists finally disseminated DUE criteria and reports to prescribe and improve RUAP in TOIO at the hospital through the Drug and Therapeutics Committee (DTC). Conclusion The study demonstrated that application of pharmacist- directed DUE is a useful strategy to detect, supervise and help correct challenges encountered during antibiotic prophylaxis in TOIO.

OBJECTIVESHepatitis E virus (HEV) is an emerging pathogen. We evaluated the seroprevalence of HEV infection among swine farmers and the general population in Taiwan, a nonendemic country.METHODSWe conducted a cross-sectional seroepidemiologic study in rural Taiwan in 2012 and 2013. The study included swine farmers, health examination attendees, pregnant women, and students. A commercial enzyme-linked immunosorbent assay was used to detect immunoglobulin G (IgG) and IgM against HEV. Pertinent information was collected using a questionnaire.RESULTSIn total, 660 participants were enrolled in the study, including 156 swine farmers, 314 health examination attendees, 100 pregnant women, and 90 students. IgG anti-HEV was detected in 29.5% of swine farmers, 11.5% of health examination attendees, 2% of pregnant women, and 1.1% of students. Two subjects were positive for IgM anti-HEV. Logistic regression analysis revealed that swine farmers had an approximately 3.5-fold increased risk (odds ratio [OR], 3.46; 95% confidence interval [CI], 1.91-6.27; pCONCLUSIONHEV infection is prevalent in Taiwan. The seroprevalence of HEV infection is high in swine farmers and in the elderly population.

To compare the risk of respiratory syncytial virus (RSV)-associated hospitalization and analyze the epidemiology of RSV infection in patients with cyanotic and acyanotic congenital heart disease (CHD), we analyzed the nationwide health insurance database from 2005-2010.This study included 1050 patients with cyanotic CHD and 7077 patients with acyanotic CHD. Patients with acyanotic CHD were further classified into hemodynamically significant (hs)-acyanotic and non-hs-acyanotic groups according to whether they underwent surgery or took at least 2 anticongestive medications.RSV-associated hospitalization was higher in the cyanotic group than in hs-acyanotic and non-hs-acyanotic groups both before 1 year of age (4.8% vs 2.1% vs 1.5%, P.001) and between 1 and 2 years of age (0.9% vs 0.56% vs 0.14%, P = .003). The hospitalization duration, intensive care, ventilator support prevalence, hospitalization cost, and mortality rate were significantly higher in the cyanotic group than in the other 2 groups. Logistic regression revealed that cyanotic CHD was the most significant risk factor for the ventilator support and RSV-associated mortality. In both patients with cyanotic and acyanotic CHD, RSV-associated hospitalization rate was higher in patients aged younger than 1 year and in spring and autumn in Taiwan, a subtropical country.The results show that patients with cyanotic CHD have a higher risk of severe RSV infection than do those with acyanotic CHD. RSV prophylaxis is more important and may reduce costs more for patients with cyanotic CHD.

Objective To delineate whether serotype 19A invasive pneumococcal disease (IPD) comprised significantly more necrotizing pneumonia and empyema in children, we compared the clinical characteristics between serotype 19A and non-19A IPD. Methods Between January 2007 and December 2011, cases of children with IPD who were treated at the National Taiwan University Hospital were reviewed. Patients were assigned to the 19A group or the non-19A group based on the serotype. Their demographic data, clinical course, laboratory results, diagnosis, complications, and sequelae were collected and analyzed. Results Overall, 27 patients were included in the 19A group and 29 patients in the non-19A group. Compared with non-19A group, serotype 19A tended to cause IPD in patients without major underlying diseases ( p = 0.015). Bacteremia without pneumonia or meningitis was found more frequently in the non-19A group (45% vs. 11%, p = 0.01), and pneumonia with or without empyema occurred significantly more frequently in the 19A group (89% vs. 52%, p = 0.006). Patients in the19A group had longer duration of fever (12 vs. 3 days, p = 0.01), and required more intensive care (78% vs. 41%, p = 0.01) and more video-assisted thoracoscopic surgery (74% vs. 28%, p = 0.001). Conclusion In comparison with the other serotypes, serotype 19A IPD has significantly more empyema which required more video-assisted thoracoscopic surgery and more intensive care.

Background Solitary thin-walled cavity lung cancer is a specific form of lung cancer, the diagnosis of which remains a formidable challenge. Objective By comparing the computed tomography (CT) presentations and pathological findings, the purpose of present study was to explain the possible mechanism of thin-walled cavity formation and to improve the diagnostic accuracy for this disease. Methods The medical records of eighteen patients with solitary thin-walled cavity lung cancer were analyzed retrospectively. Results Chest CT demonstrated that solitary thin-walled cavities located at pulmonary periphery, and all these cavity lesions displayed suspected malignant signs. Pathological findings after surgery confirmed these lesions were adenocarcinoma, most of which were moderately or well differentiated. Microscopic findings showed tumor cells proliferated in the surface of thin-wall cavity in nine patients and infringed bronchiolar wall in five patients. No obvious necrotic tumor cell was observed in each patient. Conclusion It was suggested some thin-walled cavities may be formed as a result of unidirectional check-valve mechanism. Together, a high index of awareness of this suspected CT signs is required for early diagnosis of this disease.

BackgroundArtemisinin and its derivatives were reported to possess strong regulatory effects on inflammation and autoimmune diseases. This study was designed to examine the therapeutic effects and underlying mechanisms of SM934, a water-soluble artemisinin analogue, on lupus-prone female NZB × NZW F(1) mice.Methodology/principal findingsNZB/W F(1) mice were treated orally with SM934 for 3 or 6 months respectively to investigate the effect on clinical manifestations and immunological correlates. To further explore the mechanisms of SM934, ovalbumin (OVA)-immunized or interferon (IFN)-γ-elicited C57BL/6 mice were used. In vivo, treatment with SM934 for 3 or 6 months significantly delayed the progression of glomerulonephritis and increased the survival rate of NZB/W F(1) mice. Clinical improvement was accompanied with decreased Th1-related anti-double-strand DNA (dsDNA) IgG2a and IgG3 Abs, serum interleukin (IL)-17, and increased Th2-related anti-dsDNA IgG1 Ab, serum IL-10 and IL-4. SM934 treatment also suppressed the accumulation of effector/memory T cells, induced the apoptosis of CD4(+) T cells, while enhancing the development of regulatory T cells in NZB/W F(1) mice. In addition, SM934 treatment promoted the IL-10 production of macrophages from NZB/W F(1) mice, OVA-immunized C57BL/6 mice and IFN-γ-elicited C57BL/6 mice. In vitro, SM934 enhanced IL-10 production from primary macrophages stimulated with IFN-γ.Conclusions/significanceThe results of this study demonstrated that artemisinin analogue SM934 had therapeutic effects on lupus-prone female NZB/W F(1) mice by inhibiting the pathogenic helper T cell development and enhancing anti-inflammatory cytokine IL-10 production.

Evaluation of the efficacy of influenza vaccines is essential for vaccine development. This study evaluated the neutralizing and hemagglutination-inhibition antibody response in subjects receiving the 2006–07 and 2007–08 seasonal influenza vaccines. ELISA-based microneutralization demonstrated a greater mean-fold increase and seroconversion rate than the hemagglutination-inhibition assay. The increase in the antibody titers against influenza H1 were higher than those against influenza H3 and influenza B, indicating that the H1 vaccine strain in the 2006–07 and 2007–08 seasons was more immunogenic. These data suggest that the neutralizing antibody response is a better measurement of influenza vaccine efficacy.

Objective SM934, an artemisinin derivative, possesses potent antiproliferative and antiinflammatory properties. The aim of this study was to examine the effects and explore the mechanisms of SM934 to treat autoimmune disease in lupus-prone female MRL/lpr mice. Methods In vitro, the effects of SM934 on the activation of polyclonal CD4+ T cells and the differentiation of naive CD4+ T cells were examined. In vivo, the preventative or therapeutic effects of SM934 in MRL/lpr mice were investigated. Ex vivo, the mechanisms of treatment were explored according to the immunologic correlates of disease. Results In vitro, SM934 inhibited interferon-γ (IFNγ) and interleukin-17 (IL-17) production from polyclonal CD4+ T cells activated by T cell receptor engagement and the differentiation of naive CD4+ T cells into Th1 and Th17 cells, but not Treg cells. In vivo, 12-week-old MRL/lpr mice treated with SM934 for 4 weeks showed significantly ameliorated proteinuria and renal lesion severity; decreased levels of blood urea nitrogen, serum IFNγ, and serum anti–double-stranded DNA antibodies; decreased spleen size; and a lower percentage of CD3+B220+CD4−CD8− T cells; 16-week-old MRL/lpr mice treated with SM934 for 8 weeks avoided severe proteinuria and survived longer. Ex vivo, SM934 treatment elevated the percentage of Treg cells, inhibited the development of Th1 and Th17 cells, and impeded the comprehensive activation of STAT-1, STAT-3, and STAT-5 proteins in splenocytes. Conclusion Taken together, the results of this study demonstrated that the artemisinin analog SM934 had therapeutic effects in lupus-prone female MRL/lpr mice by inhibiting both Th1 cell and Th17 cell responses. Moreover, this study indicated that both IFNγ and IL-17 are required for the elicitation and development of murine lupus.

To observe the clinical efficacy of acupoint-catgut-embedding therapy combined conventional western medication on chronic obstructive pulmonary disease (COPD) at stable stage due to lung and kidney deficiency.The cases were randomized into observation group and control group, 30 cases in each one. In control group, the conventional western medication was administered. In observation group, on the basis of conventional western medication, the catgut-embedding therapy was applied at Dingchuan (EX-B 1), Feishu (BL 13), Shenshu (BL 23), Fenglong (ST 40) and Zusanli (ST 36). The total attack frequency of acute exacerbation of COPD (AECOPD), the attack frequency of AECOPD at moderate or above moderate stage and TCM syndrome score were compared before treatment and 6 months after treatment in two groups.The total effective rate was 93.3% (28/30) in observation group and was 90.0% (27/30) in control group, indicating equivalent efficacy between two groups. 6 months after treatment, in two groups, the total attack frequency of AECOPD and the attack frequency of AECOPD at moderate or above moderate stage were reduced remarkably as compared with those before treatment (P0.01, P0.05). The total attack frequency of AECOPD in observation group was reduced remarkably as compared with that in control group (P0.05). The scores of cough, expectoration and chest oppression as well as the total score of TCM syndrome were reduced remarkably after treatment in observation group (all P0.01).Integrated therapy of acupoint-catgut-embedding and conventional medication has similar efficacy as simple medication. But, the combination of acupoint-catgut-embedding therapy and western medication can reduce the attack frequency of AECOPD and improve in cough, chest oppression and other symptoms in patients with COPD at stable stage effectively.

To observe the alteration ultraviolet radiation (UVR) of skin's tolerance after its exposure to the small dose of UVR under the protection of sunscreen.Eleven subjects who applied sunscreen were exposed to 0.75 dose minimal persistent pigment darkening (MPPD) and minimal erythema dose (MED) by the Phototherapy Unit for 4 weeks. Each week their MPPDs and MEDs were measured by solar simulator. Meanwhile, SPECTCOLOMETER® and VISIOSCAN VC98® were used to detect the test areas and control areas.The values of MPPD and MED increased significantly after the exposure to UVR. But there were no visible changes on the surface of skin's texture.With the protection of sunscreen, the UVR tolerance of skin was greatly increased after the skin's exposure to the small dose UV.

Background/PurposeEnterovirus 71 (EV71) infection may cause severe neurological and cardiopulmonary complications, especially in preschool children. This study is to investigate the seroprevalence and seroconversion of EV71, and the crossprotection of EV71 antibody against other enteroviruses among kindergarteners.MethodsOverall 228 children in a public kindergarten were enrolled during two academic years, 2006 and 2007, in Taipei, Taiwan and we measured their EV71 neutralizing antibody. When the participants had herpangina; hand, foot and mouth disease (HFMD); febrile illness or respiratory symptoms, throat swabs were sampled and processed for viral culture and enterovirus real-time reverse transcriptase polymerase chain reaction (RT-PCR). Questionnaires, completed by the participants’ guardians, surveyed the history of allergy and annual incidence of symptoms related to enterovirus infection.ResultsSeropositive rates of EV71 were 20% (32/163) in 2006 and 6% (4/65) in 2007. The rate of EV71 seropositivity increased with age (p

Background/Purpose In influenza B infection, viral load is believed to be related to the severity of clinical illness. The correlation between viral load and symptoms is not known. We conducted a study to assess the relationship between virus load and clinical features in children infected with influenza B, in the hope that clinical features could be used as surrogate markers of viral load to guide treatment. Methods Between December 2006 and February 2007, 228 patients with fever and respiratory symptoms were prospectively enrolled in our tertiary hospital-based study. Real-time reverse transcription polymerase chain reaction (RT-PCR) was performed to determine viral load. Results Real-time RT-PCR was positive for influenza B in 76 patients. Using virus culture as the gold standard, the sensitivity and specificity were 95% and 87%, respectively. Influenza culture positive rate significantly correlated with viral load ( p = 0.03). The median copy number of influenza B virus in the 76 RT-PCR positive patients was 9735 copies/ml (range 4.8×10 1 –2.0×10 6 copies/ml). Samples obtained later in the clinical course tended to have lower viral load ( p = 0.7), while patient age ( p = 0.72) and fever duration ( p = 0.96) positively related to viral load. In patients >3 years of age, myalgia was related to statistically lower viral loads (14300 vs. 1180; p = 0.025). Patients with chills tended to have higher viral loads (72450 vs. 7640; p = 0.1). Patients with abdominal pain tended to have lower viral loads (1998 vs. 12550; p = 0.06). Conclusion Culture rate positively correlated with viral load. Patients with myalgia had a lower viral load.

Immunogenicity and reactogenicity of primary vaccination with combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus (DTPa-HBV-IPV) vaccine when co-administered with Haemophilus influenzae (Hib) conjugate vaccine were assessed in 60 healthy infants. Infants received HBV vaccine at birth, then DTPa-HBV-IPV and Hib vaccines at age 1.5 months, 3.5 months and 6 months. Blood samples were collected before the first DTPa-HBV-IPV and Hib vaccine doses and 1 month after dose 3. Reactogenicity was assessed using diary cards. One month after primary vaccination, all infants were seroprotected/seropositive against all vaccine antigens evaluated. The poliovirus antigen could not be evaluated. The vaccines were well tolerated. No case of fever39.0 °C was reported. No serious adverse events were considered related to vaccination. Primary vaccination with DTPa-HBV-IPV and Hib vaccines was immunogenic and well tolerated. Combined vaccines, such as this pentavalent vaccine, minimize the number of injections and vaccination visits required to complete primary vaccination, and provide choice and flexibility for physicians and vaccine providers.

Despite proven good efficacy of pneumococcal conjugated vaccine in preventing invasive pneumococcal disease, breakthrough infections remain a noticeable problem with significant morbidity and mortality, especially in selected high-risk groups. We present a 2-year-old girl with infantile spasm, who was treated with antiepileptic drugs and adrenocorticotropic hormone (ACTH). Vaccination with three doses 7-valent pneumococcal conjugate vaccine had been completed one month before ACTH therapy. Two months after ACTH therapy, she suffered from fever, cough, and decreased activity. Streptococcus pneumoniae, serotype 6B, was detected in blood culture. Vaccine failure could be possibly due to ACTH therapy.

Herpes zoster, a common disease, has an important impact on the health of adults, particularly the elderly, and the health system. This study evaluated the disease burden and epidemiological characteristics of herpes zoster in Taiwan. Using herpes zoster-related ICD-9-CM codes used on Taiwan's National Health Insurance claims, we analyzed overall and age group differences in incidence, complications, utilization of healthcare facilities, lengths of stay, and cost of their medical care in Taiwan's population from 2000 to 2005. The overall annual incidence of zoster was 4.97 cases per 1000 people, with women having a significantly higher incidence than men (5.20 per 1000 vs. 4.72 per 1000, p

The epidemiology of coxsackievirus has rarely been investigated in Taiwan. This study was performed to ascertain the epidemiological and clinical characteristics of coxsackievirus infections in Taiwan.457 patients treated at a medical center in northern Taiwan who were positive for coxsackievirus were enrolled in this retrospective study. Patients' medical charts were reviewed for clinical diagnosis, physical examination, laboratory findings, and clinical manifestations.Three serotypes of coxsackievirus A (A9, 5.3%; A10, 7.2%; A16, 87.5%) were identified among 265 patients, 27.4% of whom were admitted to hospital. The mean (+/- standard deviation [SD]) duration of fever and hospital stay was 2.6 +/- 0.5 days and 4.0 +/- 2.1 days, respectively. Complications were noted in 14 patients (5.3%), all of which involved the central nervous system (CNS). All 6 serotypes of coxsackievirus B (B1, 2.6%; B2, 7.8%; B3, 55.7%; B4, 2.1%; B5, 12.5%; B6, 1.0%; non-typable, 18.2%) were identified in 192 patients, 45.3% of whom were admitted to hospital. The mean (+/- SD) duration of fever and hospital stay was 4.1 +/- 1.0 and 3.4 +/- 0.9 days, respectively. Thirty seven patients (19.3%) had complications, including 34 with CNS involvement. Patients with coxsackievirus B infection had higher hospital admission rates (p0.001), more CNS involvement (p0.001), and longer fever duration (p0.001) than those with coxsackievirus A infection. Patients with coxsackievirus A infection tended to have more skin manifestations (p0.001) and oral ulcers (p0.001).The most common serotypes were coxsackieviruses A16 and B3. Patients with coxsackievirus B infection were more likely to be admitted to hospital, had longer fever duration, and more CNS involvement than patients with coxsackievirus A infection.

Pneumococcal/lobar pneumonia and empyema have an important impact on the health of children worldwide. There has been no epidemiological study of pneumococcal/lobar pneumonia and empyema in Taiwan, a middle-income Asian population. Using Taiwan’s National Health Insurance database, we collected and analyzed data obtain from medical care claims related to pneumococcal/lobar pneumonia and empyema for children below the 18 years old from 1997 to 2004. We found the annual population-based incidence to have significant year to year increases and the average annual incidences of pneumococcal/lobar pneumonia and empyema in children under five to be 44.9 and 10.5 episodes per 100,000 children-year, respectively. About 64% of children with pneumococcal/lobar pneumonia and empyema were under 5 years old. Children 4 to 5 years old had the highest incidences of both pneumococcal/lobar pneumonia and empyema. Incidence was the highest each spring. The odds ratio of the case fatality among pneumococcal/lobar pneumonia patients complicated with empyema to those without was 118 (95% confidence interval 28–492). In conclusion, the population-based incidences of pneumococcal/lobar pneumonia and empyema among children under five in Taiwan were 44.9 and 10.5 episodes per 100,000 children-year, respectively, and 4- to 5-year-old children had the highest incidences of both pneumococcal/lobar pneumonia and empyema. This population might benefit from a universal pneumococcal vaccination program which might cover about 70% of invasive pneumococcal diseases in Taiwanese children under 5 years old.

Background/PurposeThis aim of this study was to assess the clinical manifestations, the microorganisms involved and their antibiotic resistance in children hospitalized due to acute lobar nephronia (ALN) and non-ALN community-acquired urinary tract infections (UTIs).MethodsWe retrospectively reviewed the records of 265 previously healthy children hospitalized due to a first-episode of community-acquired febrile UTI between July 2004 and June 2007. Based on the results of renal ultrasonography and computed tomography, they were divided into ALN and non-ALN groups. Their demographic and clinical characteristics, distribution of microorganisms, and their antimicrobial resistance were analyzed.ResultsOf the total number of cases of children admitted with a first-episode community-acquired UTI, 19.2% (n=51) were diagnosed as ALN. Children with ALN were older (1.86 years vs. 0.81 years; p < 0.01), had longer periods of fever before admission (4.7 days vs. 1.4 days; p < 0.01), higher peak body temperatures (39.5°C vs. 38.9°C; p < 0.01), higher white cell counts (18.86 × 109/L vs. 15.08 × 109/L; p < 0.01) and higher C-reactive protein levels (9.0 mg/dL vs. 3.5 mg/dL; p < 0.01) compared with non-ALN children. Fever also persisted for longer after the start of antibiotic treatment in the ALN children (2.7 days vs. 1.4 days: p < 0.01) and they required longer hospital stays and incurred higher medical costs. The major pathogen found in ALN was E. coli (90%). The E. coli isolated from ALN children was more resistant to cotrimoxazole and ciprofloxacin than those from non-ALN children.ConclusionALN is not uncommon in children with a first-episode febrile UTI. They have a prolonged clinical course, higher inflammatory parameters, longer hospital stays and incur higher medical costs. E. coli is the major pathogen isolated from these children.

Campylobacter infection is recognized as a major cause of acute enteritis in humans. The clinical characteristics may vary in different countries. This study investigated the clinical manifestations of pediatric Campylobacter enteritis in a medical center in northern Taiwan.This was a retrospective review of Campylobacter enteritis infections at National Taiwan University Hospital, Taipei, Taiwan, from January 2000 to December 2006. All children who tested positive for Campylobacter, isolated from stool samples, were included in the study. Data collected and evaluated included the species of Campylobacter, age, gender, underlying disease, travel history, clinical manifestations and laboratory data.A total of 104 patients had enteric campylobacteriosis. Campylobacter coli was grown from 24 patients (23.1%), while Campylobacter jejuni was found in 80 patients (76.9%). More than half of the infections (60.6%) occurred in children less than 5 years old. The male-to-female ratio was 2.46:1. Fifteen patients had underlying diseases (14.4%), such as hematologic malignancy, solid organ transplantation and liver cirrhosis. Watery diarrhea (93.2%), abdominal pain (92.0%), fever (81.2%), and vomiting (46.1%) were the most common clinical manifestations. Three episodes of campylobacteriosis appeared to be imported from Southeast Asia and 3 were acquired nosocomially. One patient, who did not have any underlying disease, developed Campylobacter bacteremia. No Guillain-Barre syndrome was noted in our patients and none of our patients died due to campylobacteriosis. While both diseases had similar clinical manifestations, infections caused by C. coli seemed to be more severe than those caused by C. jejuni, as evidenced by a higher incidence of decreased activity and pus cells in the stool in patients infected with C. coli.Even in patients with bacteremia or underlying disease, enteric campylobacteriosis usually runs a benign course regardless of treatment with antimicrobial agents in children in northern Taiwan.

Natural product seselin and related derivatives with an angular pyranocoumarin skeleton were synthesized from 8-acetyl-7-hydroxycoumarins by condensation with acetone, reduction, and dehydration successively under mild conditions with total yield of50%. Twelve seselin derivatives were tested by the writhing response assay induced by acetic acid at a dose of 40 mg x kg(-1). Seselin (4a) and 4,8,8-trimethyl-9,9-dihydro-pyran[2,3-f] chromene-2,10-dione (2b) showed obviously antinociceptive activity with inhibitory effect of 85% and 50%, respectively, more or quite potent than aspirin in the same assay, suggesting that seselin derivatives could be a novel kind of potential antinociceptive agents.