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In spring, windblown dust storms originating in the deserts of Mongolia and China make their way to Taipei city. These occurrences are known as Asian dust storm (ADS) events. These ADS events lead to enhanced PM(10) levels over that contributed by the usual local sources. The objective of this study was to assess the possible associations of PM(10) with hospital admissions for chronic obstructive pulmonary disease (COPD) in Taipei, Taiwan, during the period 1996-2001. We identified 54 dust storm episodes that were classified as index days. Daily COPD admissions on the index days were compared with admissions on the comparison days. We selected 2 comparison days for each index day, 7 days before the index days and 7 days after the index days. The effects of dust storms on hospital admissions for COPD were prominent 3 days after the event (relative risk = 1.057; 95% confidence interval = 0.982-1.138). However, the association was not statistically significant. There may not have been enough power to detect associations resulting from the inadequate sample size of COPD admissions on ADS events days. However, It seems worthwhile to pay more attention to the ADS events and health in the future.

Biliary atresia is the most common cause of death from liver disease in children. Although the Kasai operation before 60 days of age can significantly improve prognosis, delay in referral and surgery remains a formidable problem worldwide because of difficulties in differentiating it from benign prolonged neonatal jaundice. We established a universal screening system using an infant stool color card to promote the early diagnosis and treatment of biliary atresia. After a pilot regional study in 2002–2003, a national stool color screening system was established by integrating the infant stool color card into the child health booklet given to every neonate in Taiwan since 2004. Within 24 hours of the discovery of an abnormal stool color, this event is reported to the registry center. The annual incidence of biliary atresia per 10,000 live births in 2004 and 2005 was 1.85 (40/216,419) and 1.70 (35/205,854), respectively. The sensitivity of detecting biliary atresia using stool cards before 60 days of age was 72.5% in 2004, which improved to 97.1% in 2005. The national rate of the Kasai operation before 60 days of age increased from 60% in 2004 to 74.3% in 2005. The jaundice-free rate (

Background The incidence of end-stage renal disease (ESRD) in Taiwan is the highest in the world. However, epidemiological features of earlier chronic kidney disease (CKD) have not been investigated. Methods Since implementation of the National Health Insurance Program in 1995, more than 96% of the population in Taiwan has been enrolled. A nationally representative cohort of 200,000 individuals randomly sampled from the National Health Insurance enrollees was followed up from 1996 to 2003. Clinical conditions were defined by using diagnostic codes. The prevalence and incidence of clinically recognized CKD were assessed. We also identified risk factors associated with the development of CKD. Results The prevalence of clinically recognized CKD increased from 1.99% in 1996 to 9.83% in 2003. The overall incidence rate during 1997 to 2003 was 1.35/100 person-years. The multivariate model indicates that age is a key predictor of CKD, with an odds ratio of 13.95 for the group aged 75-plus years compared with the group younger than 20 years. Other factors associated with increased risk for the development of CKD include diabetes, hypertension, hyperlipidemia, and female sex. Conclusion The prevalence and incidence of CKD in Taiwan are relatively high compared with other countries. Our finding provides a reasonable explanation for the subsequent epidemic of ESRD in Taiwan. Further study is needed to identify the entire burden of CKD and the effectiveness of risk-factor modification.

Biliary tract infection is associated with high mortality. This study investigated the effect of glucocorticoid pretreatment on lipopolysaccharide (LPS)-induced cholangitis.Rats undergoing either sham operation or ligation of the extrahepatic bile duct (BDL) for 2 weeks were randomly assigned to receive intravenous injections of dexamethasone (DX) or normal saline (NS) prior to infusing LPS into the biliary tract. The plasma levels of tumor necrosis factor-alpha (TNFalpha), chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) as well as liver mRNA expression of MCP-1 and MIP-2 were determined. Infiltration of monocytes, Kupffer cells, and neutrophils in rat liver were studied with immunohistochemistry. Oxidative liver injury was measured by the malondialdehyde (MDA) content.Dexamethasone pretreatment resulted in significantly decreased plasma levels of TNFalpha at 1 hour, MCP-1 and MIP-2 at 2 and 3 hours, and decreased liver MCP-1 mRNA expression at 3 hours following LPS infusion in BDL-DX rats than in BDL-NS rats. The number of inflammatory cells in the liver was significantly different between sham- and BDL-treated rats but was not affected by DX pretreatment. Pretreatment with DX resulted in significantly decreased liver MDA contents in the BDL-DX group than that in the BDL-NS group. Jaundiced rats pretreated with 5 mg DX prior to infusion of 1 g of LPS were 6.8 times more likely to survive than those that were not pretreated.Pretreatment of jaundiced, LPS-treated rats with a supraphysiological dose of dexamethasone may rescue their lives by suppression of chemokine expression and alleviation of oxidative liver injury.

There is now substantial evidence that reduced expression of neuronal nitric oxide synthase (nNOS) is implicated in the pathogenesis of infantile hypertrophic pyloric stenosis (IHPS). This study aimed to investigate the role of plasma nitric oxide (NO) in patients with IHPS. Blood and pylorous biopsies of 13 IHPS patients were examined. The control group consisted of 19 age-matched healthy infants and 22 age-matched acute gastroenteritis patients. Plasma nitrite (NO2 –) and nitrate (NO3 –) levels were detected with an NO analyzer. Pylorus biopsies of 13 IHPS patients were examined for nitric oxide synthase isoform expression. Plasma nitrite levels in the 13 IHPS patients were significantly lower than in the age-matched healthy controls (0.97 ± 0.19 vs. 3.53 ± 0.79μ M; P < 0.001) and the acute gastroenteritis controls (0.97 ± 0.19 vs.1.39 ± 0.45μ M; P = 0.006). Decreased expression of nNOS in the nerve fibers of the pylorus circular muscle was found in the 13 IHPS patients. The decreased plasma nitrite levels rose to the normal range (3.27 ± 0.77 M) after pyloromyotomy. There was no significant correlation between plasma nitrite levels and muscle wall thickness in IHPS patients. We conclude that NO is implicated in the occurrence of IHPS and the plasma nitrite level is valuable for the diagnosis of IHPS.

BackgroundPrenatal dexamethasone exposure has been reported to increase allergy potential in childhood possibly by interference with normal immunological development in utero. This study investigated the effects of prenatal dexamethasone on T helper cell immune responses in a rat model.MethodsPregnant rats received either dexamethasone 0.1 mg/kg/day or normal saline from gestational day 14-21. Off-springs were cared for by their biological mother, or cross-fostered by the opposing group. Spleen and blood samples were collected at post-natal day 7 and 120 and tested for mRNA expression and plasma cytokine levels of Th1/Th2/Th17 immune response.ResultsBoth Th1 (T-bet) and Th2 (GATA-3) mRNA expression were shown to have a significant increase in the prenatal dexamethasone exposure group at day 120 (p0.05). The mRNA expression of Th17 (RORγt) showed a significant decrease at post-natal day 120 as well as the plasma level of IL-17A at day 7 (11.21±1.67 vs. 6.23±1.06 pg/ml, p = 0.02). Cross-fostering by a dexamethasone exposed mother resulted in a significant increase in Th1/Th2 mRNA expression (pConclusionsPrenatal dexamethasone exposure increased Th1, Th2 and decreased Th17 expression. Cross-fostering by a dexamethasone exposed mother results in more prominent increase of Th1 and Th2 expression.

Obesity and related disorders have increased concurrently with an increased consumption of saturated fatty acids. We examined whether post-weaning high fat (HF) diet would exacerbate offspring vulnerability to maternal HF-induced programmed hypertension and kidney disease sex-specifically, with a focus on the kidney. Next, we aimed to elucidate the gene–diet interactions that contribute to maternal HF-induced renal programming using the next generation RNA sequencing (NGS) technology. Female Sprague-Dawley rats received either a normal diet (ND) or HF diet (D12331, Research Diets) for five weeks before the delivery. The offspring of both sexes were put on either the ND or HF diet from weaning to six months of age, resulting in four groups of each sex (maternal diet/post-weaning diet; n = 5–7/group): ND/ND, ND/HF, HF/ND, and HF/HF. Post-weaning HF diet increased bodyweights of both ND/HF and HF/HF animals from three to six months only in males. Post-weaning HF diet increased systolic blood pressure in male and female offspring, irrespective of whether they were exposed to maternal HF or not. Male HF/HF offspring showed greater degrees of glomerular and tubular injury compared to the ND/ND group. Our NGS data showed that maternal HF diet significantly altered renal transcriptome with female offspring being more HF-sensitive. HF diet induced hypertension and renal injury are associated with oxidative stress, activation of renin-angiotensin system, and dysregulated sodium transporters and circadian clock. Post-weaning HF diet sex-specifically exacerbates the development of obesity, kidney injury, but not hypertension programmed by maternal HF intake. Better understanding of the sex-dependent mechanisms that underlie HF-induced renal programming will help develop a novel personalized dietary intervention to prevent obesity and related disorders.

MicroRNA-29 (miR-29) is found to modulate hepatic stellate cells’ (HSCs) activation and, thereby, reduces liver fibrosis pathogenesis. Histone methyltransferase regulation of epigenetic reactions reportedly participates in hepatic fibrosis. This study is undertaken to investigate the miR-29a regulation of the methyltransferase signaling and epigenetic program in hepatic fibrosis progression. miR-29a transgenic mice (miR-29aTg mice) and wild-type littermates were subjected to bile duct-ligation (BDL) to develop cholestatic liver fibrosis. Primary HSCs were transfected with a miR-29a mimic and antisense inhibitor. Profibrogenic gene expression, histone methyltransferases and global genetic methylation were probed with real-time quantitative RT-PCR, immunohistochemical stain, Western blot and ELISA. Hepatic tissue in miR-29aTg mice displayed weak fibrotic matrix as evidenced by Sirius Red staining concomitant with low fibrotic matrix collagen 1α1 expression within affected tissues compared to the wild-type mice. miR-29a overexpression reduced the BDL exaggeration of methyltransferases, DNMT1, DNMT3b and SET domain containing 1A (SET1A) expression. It also elevated phosphatase and tensin homolog deleted on chromosome 10 (PTEN) signaling within liver tissue. In vitro, miR-29a mimic transfection lowered collagen 1α1, DNMT1, DNMT3b and SET1A expression in HSCs. Gain of miR-29a signaling resulted in DNA hypomethylation and high PTEN expression. This study shines a new light on miR-29a inhibition of methyltransferase, a protective effect to maintain the DNA hypomethylation state that decreases fibrogenic activities in HSC. These robust analyses also highlight the miR-29a regulation of epigenetic actions to ameliorate excessive fibrosis during cholestatic liver fibrosis development.

In cases of arginine depletion, lymphocyte proliferation, cytokine production and CD3ζ chain expression are all diminished. In addition to myeloid suppressor cells, polymorphonuclear cells (PMN) also exert T-cell immune suppressive effects through arginase-induced l-arginine depletion, especially during pregnancy. In this study, we investigated how arginase/l-arginine modulates neonatal lymphocyte proliferation. Results showed that the neonatal plasma l-arginine level was lower than in adults (48·1 ± 11·3 versus 86·5 ± 14·6 μm; P = 0·003). Neonatal PMN had a greater abundance of arginase I protein than adult PMN. Both transcriptional regulation and post-transcriptional regulation were responsible for the higher arginase I expression of neonatal PMN. Exogenous l-arginine enhanced neonate lymphocyte proliferation but not that of adult cells. The RNA-binding protein HuR was important but was not the only modulation factor in l-arginine-regulated neonatal T-cell proliferation. l-Arginine-mediated neonatal lymphocyte proliferation could not be blocked by interleukin-2 receptor blocking antibodies. These results suggest that the altered arginase/l-arginine cascade may be one of the mechanisms that contribute to altered neonatal immune responses. Exogenous l-arginine could enhance neonate lymphocyte proliferation through an interleukin-2-independent pathway.

Adult mesenchymal stem cell (MSC)-conducted mitochondrial transfer has been recently shown to rescue cellular bioenergetics and prevent cell death caused by mitochondrial dysfunction. Wharton's jelly-derived MSCs (WJMSCs) harvested from postpartum umbilical cords are an accessible and abundant source of stem cells. This study aimed to determine the capability of WJMSCs to transfer their own mitochondria and rescue impaired oxidative phosphorylation (OXPHOS) and bioenergetics caused by mitochondrial DNA defects. To do this, WJMSCs were co-cultured with mitochondrial DNA (mtDNA)-depleted ρ(0) cells and the recapture of mitochondrial function was evaluated. WJMSCs were shown to be capable of transferring their own mitochondria into ρ(0) cells and underwent interorganellar mixture within these cells. Permissive culture media (BrdU-containing and pyruvate- and uridine-free) sieved out a survival cell population from the co-cultured WJMSCs (BrdU-sensitive) and ρ(0) cells (pyruvate/uridine-free). The survival cells had mtDNA identical to that of WJMSCs, whereas they expressed cellular markers identical to that of ρ(0) cells. Importantly, these ρ(0)-plus -WJMSC-mtDNA (ρ(+W)) cells recovered the expression of mtDNA-encoded proteins and exhibited functional oxygen consumption and respiratory control, as well as the activity of electron transport chain (ETC) complexes I, II, III and IV. In addition, ETC complex V-inhibitor-sensitive ATP production and metabolic shifting were also recovered. Furthermore, cellular behaviors including attachment-free proliferation, aerobic viability and OXPHOS-reliant cellular motility were also regained after mitochondrial transfer by WJMSCs. The therapeutic effect of WJMSCs-derived mitochondrial transfer was able to stably sustain for at least 45 passages. In conclusion, this study suggests that WJMSCs may serve as a potential therapeutic strategy for diseases linked to mitochondrial dysfunction through the donation of healthy mitochondria to cells with genetic mitochondrial defects.

Prenatal glucocorticoid exposure causes brain damage in adult offspring; however, the underlying mechanisms remain unclear. Melatonin has been shown to have beneficial effects in compromised pregnancies. Pregnant Sprague-Dawley rats were administered vehicle (VEH) or dexamethasone between gestation days 14 and 21. The programming effects of prenatal dexamethasone exposure on the brain were assessed at postnatal days (PND) 7, 42, and ∼120. Melatonin was administered from PND21 to the rats exposed to dexamethasone, and the outcome was assessed at ∼PND120. In total, there were four groups: VEH, vehicle plus melatonin (VEHM), prenatal dexamethasone-exposure (DEX), and prenatal dexamethasone exposure plus melatonin (DEXM). Spatial memory, gross hippocampal morphology, and hippocampal biochemistry were examined. Spatial memory assessed by the Morris water maze showed no significant differences among the four groups. Brain magnetic resonance imaging showed that all rats with prenatal dexamethasone exposure (DEX + DEXM) exhibited increased T2-weighted signals in the hippocampus. There were no significant differences in the levels of mRNA expression of hippocampal reln, which encodes reelin, and GAD1, which encodes glutamic acid decarboxylase 67, at PND7. At both PND42 and ∼PND120, reln and GAD1 mRNA expression levels were decreased. At ∼PND120, melatonin restored the reduced levels of hippocampal reln and GAD1 mRNA expression in the DEXM group. In addition, melatonin restored the reln mRNA expression levels by (1) reducing DNA methyltransferase 1 (DNMT1) mRNA expression and (2) reducing the binding of DNMT1 and the methyl-CpG binding protein 2 (MeCP2) to the reln promoter. The present study showed that prenatal dexamethasone exposure induced gross alterations in hippocampal morphology and reduced the levels of hippocampal mRNA expression of reln and GAD1. Spatial memory was unimpaired. Thus, melatonin had a beneficial effect in restoring hippocampal reln mRNA expression by reducing DNMT1 and MeCP2 binding to the reln promoter.

Parkinson disease (PD) is a complex neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons. Mitochondrial dysfunction, oxidative stress or protein misfolding and aggregation may underlie this process. Autophagy is an intracellular catabolic mechanism responsible for protein degradation and recycling of damaged proteins and cytoplasmic organelles. Autophagic dysfunction may hasten the progression of neuronal degeneration. In this study, resveratrol promoted autophagic flux and protected dopaminergic neurons against rotenone-induced apoptosis. In an in vivo PD model, rotenone induced loss of dopaminergic neurons, increased oxidation of mitochondrial proteins and promoted autophagic vesicle development in brain tissue. The natural phytoalexin resveratrol prevented rotenone-induced neuronal apoptosis in vitro, and this pro-survival effect was abolished by an autophagic inhibitor. Although both rotenone and resveratrol promoted LC3-II accumulation, autophagic flux was inhibited by rotenone and augmented by resveratrol. Further, rotenone reduced heme oxygenase-1 (HO-1) expression, whereas resveratrol increased HO-1 expression. Pharmacological inhibition of HO-1 abolished resveratrol-mediated autophagy and neuroprotection. Notably, the effects of a pharmacological inducer of HO-1 were similar to those of resveratrol, and protected against rotenone-induced cell death in an autophagy-dependent manner, validating the hypothesis of HO-1 dependent autophagy in preventing neuronal death in the in vitro PD model. Collectively, our findings suggest that resveratrol induces HO-1 expression and prevents dopaminergic cell death by regulating autophagic flux; thus protecting against rotenone-induced neuronal apoptosis.

Nonalcoholic fatty liver disease patients are characterized by hepatic steatosis. Prenatal glucocorticoid overexposure can result in steatosis. In this study, we aimed to determine the mechanism and cellular apoptosis of prenatal glucocorticoid overexposure in rats and whether melatonin can rescue the prenatal glucocorticoid-induced steatosis and apoptosis in neonatal rats. Pregnant Sprague-Dawley rats at gestational days 14 to 21 were administered dexamethasone. Acute effects of prenatal programming liver were assessed at postnatal day 7. The expression of proteins involved in the apoptotic and methylation pathways was analyzed by RT-PCR and Western blotting. Apoptosis and steatosis were examined by histology staining. The liver steatosis and apoptosis were increased in prenatal glucocorticoid group more than in control group and decreased in melatonin group. The expression of leptin decreased in prenatal glucocorticoid and increased in melatonin group by liver RT-PCR and Western blot study. Caspase 3, TNF-αproteins expression, and TUNEL stains increased in prenatal glucocorticoid compared with control and decreased in melatonin group. The liver histone deacetylase, DNA methyltransferase activity, and DNA methylation were increased in prenatal glucocorticoid and decreased in melatonin group. The present study showed that the prenatal glucocorticoid induced programming liver steatosis at day 7 after delivery, possibly via altered leptin expression. Melatonin can reverse the methylation of leptin and decreased liver steatosis.

Objective Small-bowel intussusception (SBI) for pediatric patients is unusual and difficult to diagnose preoperatively. This study sought to determine the sonographic findings of pediatric SBI. Methods The sonographic features and surgical findings of 13 pediatric patients (7 boys, 6 girls; age range 4 months-15 years; average age 4 years and 2 months) with SBI encountered in the authors' hospital over a 12-year period were retrospectively reviewed. Results Most of the patients presented with nonspecific symptoms, including vomiting, abdominal pain, and/or irritable crying. Sonographic screening in the emergency department revealed a doughnut or crescent-in-doughnut sign, or a multiple-concentric-rings sign for 11 of the 13 patients, and the lesions appeared short. Eight lesions were found in the paraumbilical or left abdominal regions. Sonographic measurement of the size of the lesions from these 11 patients ranged from 2 cm to 3.7 cm (average 2.77 cm). Subsequent barium enemas were performed for these 11 patients, none of which revealed colon lesions. Surgery revealed ileoileal intussusceptions for eight cases, jejunoileal for three, and jejunojejunal for the remaining two. Bowel ischemia or necrosis and pathologic lead points were demonstrated for seven and six patients, respectively, although none were recognized preoperatively. Conclusions Small-bowel intussusception is often over-looked due to nonspecific clinical presentations. Sonographic demonstration of a 2-3-cm sized, short, doughnut-like lesion, especially in the left abdomen or paraumbilical regions, should lead to strong suspicion of SBI.

Departments of *Pediatrics, †Pathology, ‡Radiology, and §Pediatric Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan Reprint Address: Mao-Meng Tiao, MD, Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, 123 Ta-Pei Road, Niao Sung Hsiang, Kaohsiung Hsien, Taiwan

We report an unusual case of simultaneous obstruction of the left pulmonary artery and descending thoracic aorta after Gianturco coil occlusion in a 15-month-old boy. The diagnosis was made by echocardiography and cardiac angiography. At surgery, thrombi coating on the protruded parts of the Gianturco coil in the pulmonary artery and aorta were found.

Overexposure to prenatal glucocorticoid (GC) disturbs hypothalamic-pituitary-adrenocortical axis-associated neuroendocrine metabolism and susceptibility to metabolic syndrome. A high-fat (HF) diet is a major environmental factor that can cause metabolic syndrome. We aimed to investigate whether prenatal GC plus a postnatal HF diet could alter immune programming in rat offspring. Pregnant Sprague-Dawley rats were given intraperitoneal injections of dexamethasone or saline at 14-21 days of gestation. Male offspring were then divided into four groups: vehicle, prenatal dexamethasone exposure, postnatal HF diet (VHF), and prenatal dexamethasone exposure plus a postnatal HF diet (DHF). The rats were sacrificed and adaptive immune function was evaluated. Compared to the vehicle, the DHF group had lower interferon gamma (IFN-γ) production by splenocytes at postnatal day 120. Decreases in H3K9 acetylation and H3K36me3 levels at the IFN-γ promoter correlated with decreased IFN-γ production. The impaired IFN-γ production and aberrant site-specific histone modification at the IFN-γ promoter by prenatal dexamethasone treatment plus a postnatal HF diet resulted in resilience at postnatal day 180. Prenatal dexamethasone and a postnatal HF diet decreased IFN-γ production through a site-specific and an age-dependent histone modification. These findings suggest a mechanism by which prenatal exposure to GC and a postnatal environment exert effects on fetal immunity programming.

Bile duct ligation (BDL)-treated rats display cholestasis and liver damages. The potential protective activity of melatonin in young BDL rats in terms of apoptosis, mitochondrial function, and endoplasmic reticulum (ER) homeostasis has not yet been evaluated. Three groups of young male Sprague-Dawley rats were used: one group received laparotomy (Sham), a second group received BDL for two weeks (BDL), and a third group received BDL and intraperitoneal melatonin (100 mg/day) for two weeks (BDL + M). BDL group rats showed liver apoptosis, increased pro-inflamamtory mediators, caspases alterations, anti-apoptotic factors changes, and dysfunction of ER homeostasis. Melatonin effectively reversed apoptosis, mainly through intrinsic pathway and reversed ER stress. In addition, in vitro study showed melatonin exerted its effect mainly through the melatonin 2 receptor (MT2) in HepG2 cells. In conclusion, BDL in young rats caused liver apoptosis. Melatonin rescued the apoptotic changes via the intrinsic pathway, and possibly through the MT2 receptor. Melatonin also reversed ER stress induced by BDL.

Accumulating evidence demonstrates that microRNA-29 (miR-29) expression is prominently decreased in patients with hepatic fibrosis, which consequently stimulates hepatic stellate cells’ (HSCs) activation. We used a cDNA microarray study to gain a more comprehensive understanding of genome-wide gene expressions by adjusting miR-29a expression in a bile duct-ligation (BDL) animal model. Methods: Using miR-29a transgenic mice and wild-type littermates and applying the BDL mouse model, we characterized the function of miR-29a with regard to cholestatic liver fibrosis. Pathway enrichment analysis and/or specific validation were performed for differentially expressed genes found within the comparisons. Results: Analysis of the microarray data identified a number of differentially expressed genes due to the miR-29a transgene, BDL, or both. Additional pathway enrichment analysis revealed that TGF-β signaling had a significantly differential activated pathway depending on the occurrence of miR-29a overexpression or the lack thereof. Furthermore, overexpression was found to elicit changes in Wnt/β-catenin after BDL. Conclusion: This study verified that an elevated miR-29a level could alleviate liver fibrosis caused by cholestasis. Furthermore, the protective effects of miR-29a correlate with the downregulation of TGF-β and associated with Wnt/β-catenin signal pathway following BDL.

Children with acute lymphoblastic leukemia (ALL) frequently present with hepatomegaly and mild liver functional impairment. Severe jaundice is rarely seen as a presenting feature. Such patients often present diagnostic dilemmas and therapeutic difficulties. Here we report a 15-year-old boy presenting with severe jaundice and hyperferritinemia, whose bone marrow smear showed B-lineage precursor ALL. We treated him with intravenous immunoglobulin, steroid, and etoposide; then his condition improved. ALL should be considered as a possible diagnosis in severely jaundiced children. Steroid and etoposide can be used as first aid when many chemotherapeutic drugs are contraindicated.

Background Mitochondria are known to be involved in cholestatic liver injury. We tested the hypothesis that glucocorticoids can modulate mitochondrial function to alleviate cholestatic liver injury. Methods A rat model of cholestasis was established by bile duct ligation (BDL), with a sham group receiving laparotomy without BDL, and a group receiving dexamethasone (DEX) treatment after BDL. Results The liver function including total bilirubin levels, alanine transaminase and aspartate transaminase activities was significantly improved in the DEX treatment group in comparison to the BDL group. There was a significant upregulation of liver peroxisome proliferator-activated receptor γ coactivator-1α and mitochondrial transcriptional factor A protein between 6 and 72 h was found in the DEX group. DEX treatment significantly down-regulated Bax, caspase 9 and caspase 3 expression induced by BDL at 24–72 h, but had little effect on the expression of caspase 8, Bcl 2, Fas and Fas-FasL complex. Consequently, the number of apoptotic liver cells in the DEX group was significantly less than in the BDL group at 72 h. Conclusion Our results indicate that glucocorticoids decreases cholestatic liver injury within hours after BDL. Early glucocorticoids treatment can enhance the mitochondrial biogenesis and modulate the intrinsic but not extrinsic pathway of apoptosis following BDL.

Background Obstructive jaundice is associated with bacterial translocation and inflammatory cytokine induction. It is unknown if toll-like receptors (TLRs) and their upstream molecule high mobility group box-1 (HMGB1) are involved in the pathogenetic mechanism and if glucocorticoid is effective in modulating the process. Materials and Methods A rat model of cholestasis by ligation of the extrahepatic bile duct (BDL) for 2 wk was created. TLRs, interferon regulatory factors (IRFs), IL-6, IL-8, antimicrobial peptide β-defensin, and cathelicidin, as well as HMGB1 expressions were studied by using real-time quantitative reverse transcription-polymerase chain reaction, immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assay (ELISA). Glucocorticoid treatment was applied to a group of BDL rats. Results Obstructive jaundice for 2 wk was associated with significant up-regulation of TLR1, 2, 4, 6, 7, and 9 mRNA expressions. There were significant increases of liver IRF5, IL-6, and β-defensin 1 mRNA levels in the BDL rats than in the sham and nonoperative control rats, which were associated with significant increase of immunoreactive IRF5 protein staining in the nucleus of Kupffer cells and neutrophils. Hepatic HMGB1 expression and release into serum were significantly elevated in the cholestatic rats than in the sham and control rats. Glucocorticoid treatment significantly decreased hepatic HMGB1 expression and release into serum, which was associated with significantly decreased hepatic TLR4 mRNA expression in the cholestatic rats. Conclusions The results indicate that obstructive jaundice may induce hepatic HMGB1 expression with activation of TLR4 and a number of downstream signaling molecules, which can be reversed by glucocorticoid administration.

Purpose The chronic effect of various analgesics on the progression of chronic kidney disease (CKD) is inconclusive. There is also lack of information on the renal safety of selective cyclooxygenase-2 (COX-2) inhibitors. This study aimed to clarify the renal risk of analgesic use in CKD patients. Methods A cohort study using a nationally representative database randomly sampled from National Health Insurance (NHI) enrollees was performed. The study population included a total of 19,163 newly diagnosed CKD patients. Clinical conditions were defined by diagnostic codes and exposure information on analgesics was derived from service claims. Cox proportional hazard model was used to assess the association between analgesic use and the risk of progression to end stage renal disease (ESRD). Results CKD patients using acetaminophen, aspirin, and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) had an increased risk for ESRD with multivariable-adjusted HRs (95%CIs) of 2.92 (2.47–3.45), 1.96 (1.62–2.36), and 1.56 (1.32–1.85), respectively. The trends toward higher risk with increasing exposure dose were significant for all classes of analgesics (all P for trend

Most infantile hypertrophic pyloric stenosis (IHPS) cases are diagnosed between 3 and 12 weeks after birth. Few data exist regarding Asian infants with IHPS who are younger than 3 weeks or are preterm. The goal of this study is to identify unusual clinical manifestations, clinical course, duration of hospital stay, and complications of Asian infants with IHPS who are preterm or younger than 3 weeks of age.From 1991 to 2004, all IHPS patients admitted to three tertiary centers in southern Taiwan were enrolled. The clinical manifestations, duration of hospital stay and complications were further compared between the IHPS patients diagnosed before and after 3 weeks; preterm and term infants.A total of 214 patients were enrolled into the study; the mean age of diagnosis was 40 days of age; the average duration of hospital stay was 6.27 days. Eighteen (8.41%) patients were diagnosed before 3 weeks of age. A significantly shorter timeframe of diagnosis, a higher rate of jaundice, a lower daily body weight gain and longer duration of hospital stay were noted in the IHPS group prior to 3 weeks compared with those in IHPS group after 3 weeks. Eighteen were preterm infants. A significantly older age of symptom onset, a lower body weight at admission, more cases diagnosed by barium meal study and higher postoperative complication rates were noted in the preterm group versus full-term infants with IHPS.The IHPS cases diagnosed before 3 weeks of age had longer duration of hospital stay. Preterm infants with IHPS had more postoperative complications.

Parkinson's disease (PD) is a progressive neurological disorder marked by nigrostriatal dopaminergic degeneration and development of cytoplasmic aggregates known as Lewy bodies. The impact of this disease is indicated by the fact that mortality is two to five times as high among affected persons as among age-matched controls. However, the cause of PD is still unknown and no cure is available at present. Several biochemical abnormalities have been described in the brains of patients with PD, including oxidative stress and mitochondrial dysfunction. Recent identification of specific gene mutations that cause PD has further reinforced the relevance of oxidative stress and mitochondrial dysfunction in the familial and sporadic forms of the disease. The proteins that are reported to be related to familial PD-PTEN-induced putative kinase 1 (PINK1), DJ-1, alpha- synuclein, leucine-rich repeat kinase 2 (LRRK2), and, possibly, parkin-are either mitochondrial proteins or are associated with mitochondria, and all are involved in pathways that elicit oxidative stress or free radical damage. Mitochondria are continually exposed to reactive oxygen species and accumulate oxidative damage more rapidly than the rest of the cell. Therefore, Parkinson's disease has been suggested to be associated with mitochondrial dysfunction. Since mitochondria are the major intracellular organelles that regulate both cell survival and death, clarifying the involvement of mitochondrial dysfunction and biogenesis during the process of PD could provide treatment strategies that might successfully intervene in the pathogenesis and slow the progression of the disease.

Background Mitochondria (mt) are highly susceptible to reactive oxygen species (ROS). In this study, we investigated the association between a region within the displacement loop (D-loop) in mtDNA that is highly susceptible to ROS and oxidative stress markers in chronic dialysis patients. We enrolled 184 chronic dialysis patients and 213 age-matched healthy subjects for comparison. Blood levels of oxidative stress markers, such as thiobarbituric acid reactive substances (TBARS) and free thiol, and the mtDNA copy number were determined. A mononucleotide repeat sequence (CCCC...CCCTCCCCCC) between nucleotides 303 and 316-318 (D310) was identified in mtDNA. Results Depending on alterations in the D310 mononucleotide repeat, subjects were categorized into 4 subgroups: 7-C, 8-C, 9 or 10-C, and T-to-C transition. Oxidative stress was higher in chronic dialysis patients, evidenced by higher levels of TBARS and mtDNA copy number, and a lower level of free thiol. The distribution of 7-C, 8-C, and 9-10C in dialysis and control subjects was as follows: 7-C (38% vs. 31.5%), 8-C (35.3% vs. 43.2%), and 9-10C (24.5% vs. 22.1%). Although there were significant differences in levels of TBARS, free thiol, and the mtDNA copy number in the D310 repeat subgroups (except T-to-C transition) between dialysis patients and control subjects, post hoc analyses within the same study cohort revealed no significant differences. Conclusion Although oxidative stress was elevated in chronic dialysis patients and resulted in a compensatory increase in the mtDNA copy number, homopolymeric C repeats in the mtDNA region (D310), susceptible to ROS, were not associated with oxidative stress markers in these patients.

End-stage renal disease is epidemic in Taiwan. Although early intervention in chronic kidney disease (CKD) has proven to be effective in modifying its clinical course, little is known about the quality and trend of CKD care in Taiwan.From a nationally representative database of 200,000 individuals, CKD patients were identified by diagnostic codes, and their medical interventions were extracted from service claims. The predictors for care delivery were analyzed in a logistic regression model.Of the 7,740 patients with CKD, only 54.8% had follow-up of renal function. Tests for anemia, calcium/ phosphorus and lipid profile were performed in 34.5%, 5.2% and 40.9% of patients, respectively. Most hypertensive CKD patients have used antihypertensive agents, but only 58.1% of them received angiotensinconverting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). Of CKD patients with diabetes, less than half had glycosylated hemoglobin measured, and only 49.7% received ACEIs/ARBs. We observed an encouraging trend in the use of ACEIs/ ARBs and in most aspects of laboratory monitoring.Management of CKD patients is suboptimal, and lack of awareness is common. Further work is needed to evaluate the impact of educational initiatives and multidisciplinary teams on outcomes in CKD patients.

There is increasing evidence that the integrity of antioxidant defenses is of vital importance in extrahepatic cholestasis, particularly with regard to the functioning of the liver's mitochondria. Although the mechanisms by which cholestasis causes oxidant/antioxidant imbalance in mitochondria are poorly understood, hepatic injury caused by cholestasis may be due to oxidative stress from the mitochondria. The injury has been observed in experimental models of cholestasis, especial in a model of biliary cholestasis established in rats with bile duct ligation (BDL). In the BDL rat model, the mitochondrial DNA copy number is changed and apoptosis is activated in the liver. In addition, Peroxisome Proliferator-activated Receptor-Coactivator-1alpha and transcriptional factor A are impaired. Compared to sham-operated rats, glutathione activity is decreased after BDL. Peroxidation of the mitochondrial phospholipids may cause cell necrosis and the level of a by-product of this peroxidation, malondialdehyde, may contribute to cell death after BDL. The disturbance of the oxidant-antioxidant balance, especially in mitochondria, may be responsible for cholestatic liver injury in cholestasis rats. This review describes recent development in the pathogenesis of cholestasis from the viewpoint of mitochondrial biogenesis and suggests possible directions for future study.

We conducted a retrospective study of both the clinical and laboratory characteristics of shigellosis in southern Taiwan.We collected shigella dysentery cases at Kaohsiung Chang Gung Memorial Hospital and Kaohsiung Veterans General Hospital from 1996 to 2005. Fifteen children and twelve adults were enrolled and their clinical presentations analyzed.Watery diarrhea (63.0%) was the most prevalent symptom in this study. Although the C-reactive protein (CRP) level was higher in patients with bloody diarrhea than those with watery diarrhea (123.5 +/-73.4 mg/L vs. 40.5 +/-36.7 mg/L, p= 0.005), there was no significant difference in the hospital stay (p= 0.072) and total number of days with fever (p= 0.981) between these 2 groups. The white blood cell (WBC) and neutrophil counts were significantly lower in patients with Shigella flexneri (S. flexneri) than those with Shigella sonnei(S. sonnei) enterocolitis (p= 0.038 and p= 0.001). WBC counts lower than 13,500/ mm(3) (OR = 3.17, 95% CI: 1.63-6.14, p= 0.005) and neutrophil counts lower than 9,400/ mm(3) (OR = 12.00, 95% CI: 1.16-123.68, p= 0.030) were more likely to be encountered in infections caused by S. flexnerithan S. sonnei. Resistance was highest to trimethoprim-sulfamethoxazole (TMP-SMX) (56%), with ampicillin (28%) second. There was no significant difference between children and adults in total number of days with fever (p= 0.532), incidence of bloody diarrhea (p= 1.000), WBC count (p= 0.177), CRP level (p= 0.858), or hospital stay (p= 0.734).Shigellosis should be considered in patients with watery diarrhea even without a contact history. There were lower blood WBC and neutrophil counts in S. flexneithan in S. sonneienterocolitis. TMP-SMX and ampicillin should be used cautiously because of high resistance. There were no specific differences in the clinical and laboratory presentations between children and adults with shigellosis.

This study investigated the feasibility of early computed tomographic (CT) evaluation and the operative results of pediatric small bowel intussusception with deteriorating ischemic or obstructive symptoms, so-called small bowel intussusception disease (SBID).Between 1988 and 1999, among 18 patients surgically proven SBID (conventional group), 12 mimicked ileocolic intussusception and were conventionally managed with abdominal radiography, ultrasonography, reduction enema, and eventually operation. Between 2000 and 2008, we applied a modified approach with inclusion of early CT evaluation if ultrasonography showed a target lesion suspicious for SBID (diameter/=3.0 cm and/or atypically located in the paraumbilical or left abdomen). Among 15 surgically proven SBID patients (early CT group), 13 underwent early operation after CT confirmation. The clinical, imaging, and operative findings were compared between the 2 groups.There were no significant differences between the 2 groups in age, gender, clinical presentations, leukocyte count, ultrasonographic features, locations of SBID, or the presence of lead points. Most patients presented with vomiting, abdominal pain, or irritable crying. In comparison with the conventional group, early CT group patients had a significantly shorter duration between admission and surgery (31.44 +/- 30.39 vs 7.47 +/- 5.95 hours; P.01) and a lower rate of bowel complications (44.4% vs 6.7%; P = .02).Pediatric SBID may present with nonspecific symptoms and may mimic ileocolic intussusception leading to delayed operative intervention. Early CT evaluation of patients with suspicious SBID ultrasonographic features is effective in avoiding futile reduction enema and significantly reducing the waiting time for operative management and the resultant incidence of bowel complications.

Early diagnosis of biliary atresia (BA) is important because the prognosis is closely related to timing of Kasai operation. The aim of this study was to test the clinical application of serum gamma-glutamyl transferase (GGT) concentration and the ratio of serum GGT to aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in differentiating BA from neonatal hepatitis (NH).Ninety-three (46 male and 47 female) cases of BA and 65 (45 male and 20 female) NH were included in this study. Serum concentrations of GGT, AST, and ALT were measured in all cholestatic infants. The results of peak GGT level, GGT/AST ratio, GGT/ALT ratio were compared between groups.The serum GGT levels were significantly higher in BA patients than those in NH patients (353.3 +/- 334.4 IU/L vs. 114.8 +/- 86 IU/L, P0.001). GGT/AST values were over 2 in 55/68 BA and 15/ 54 NH (OR = 11.0, 95% CI 4.7-25.7, P0.001). GGT/ALT values were over 2 in 54/65 BA and 19/50, NH respectively (OR = 8.0, 95% CI 3.4-19.0, P0.001). A GGT level greater than 300 IU/L had a sensitivity of 39.7% in the diagnosis of BA, GGT/AST over 2 was 80.9% and GGT/ALT over 2 was 83.1%; the specificities were 98.1%, 72.2% and 62.0%, respectively. The respective accuracies of the diagnosis of BA were 65.6%, 77.1% and 73.9%.GGT/AST ratio over 2 indicates high possibility of biliary atresia and should prompt further investigations to confirm the diagnosis.

Taiwan is currently nonendemic for hepatitis A infection, but sporadic cases are reported occasionally. The presenting symptoms of acute hepatitis A (AHA) infection in children are often nonspecific and may be easily misdiagnosed as general gastrointestinal illness.We conducted this study to identify the relevant presenting symptoms and laboratory findings of AHA in children. The medical records of all patients younger than 18 years old admitted to Kaohsiung Chang Gang Memorial Hospital from July 1986 to June 2004 under the diagnosis of AHA were reviewed. There were 29 pediatric patients admitted with the diagnosis of AHA, including 16 male patients and 13 female patients.Poor appetite, malaise, abdominal pain, vomiting and fever were the leading constitutional symptoms. Jaundice and tea-colored urine were the most relevant hepatobiliary presentations. Elevation of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, direct and indirect bilirubin was common, although other hematology and biochemistry examinations were within normal limits on most occasions. There was no mortality in our series. A slightly increasing prevalence of AHA was noted over the two decades of the study period, although it was not statistically significant.Our results found that children with AHA tended to present with non-specific gastrointestinal symptoms and acute liver function deterioration. Elevation of hepatic aminotransferase and alkaline phosphatase with cholestasis was common.

The management of biliary atresia (BA) has evolved with time. The outcome of BA treatment in the Chang Gung Memorial Hospital-Kaohsiung Medical Center had not been recorded and we addressed this issue in this study.Medical records of the 93 patients with BA who underwent Kasai portoenterostomy (KP) in the Chang Gung Memorial Hospital-Kaohsiung Medical Center from 1986 to 2005 were reviewed retrospectively. There were 46 male and 47 female patients included in this study. Sixty patients received KP before 60 days of age and 33 patients received KP after 60 days of age.Jaundice-free survival with native liver was accomplished in 29 of 60 patients who received KP before 60 days of age but in only 9 of 33 after that age (p = 0.048). Cholangitis developed in 56 patients (60.2%). Incidence of cholangitis was not significantly different between the patients free of jaundice (22/38) and those with persistent jaundice (34/55) (p = 0.704). Seven patients had single cysts and 1 had multiple cysts, with 4 being jaundice-free. Five out of 9 were free of jaundice after re-do KP. Among the 62 patients followed for more than 5 years, 32 (51.6%) survived with native liver.This study revealed that half of the patients with BA survived with their native liver for more than 5 years. Age at operation, not post-KP cholangitis or liver cysts, was the most determinant factor of BA outcome.

Choledochal cyst perforation associated with bacteria is very rare. An 11-month-old infant was admitted to hospital because of fever and bloody diarrhea. Abdominal ultrasonogram revealed a choledochal cyst. Despite antibiotic treatment with initial improvement, jaundice and abdominal tenderness developed 6 days later. Ultrasonography-guided aspiration yielded bile-stained ascites. Emergency operation confirmed the diagnosis of choledochal cyst with perforation. Blood, stool, and bile juice cultures all yielded Salmonella typhimurium. To our knowledge, it is rare that a child with choledochal cyst has systemic infection with S. typhimurium and cyst perforation. We propose that systemic Salmonella infection carries a risk of cyst perforation in patients with congenital choledochal cyst. [J Formos Med Assoc 2007;106(3 Suppl):S20-S23]

Background Recent studies have shown that microRNA-29 (miR-29) is significantly decreased in liver fibrosis and that its downregulation influences the activation of hepatic stellate cells (HSCs). In addition, inhibition of the activity of histone deacetylases 4 (HDAC4) has been shown to strongly reduce HSC activation in the context of liver fibrosis. Objectives In this study, we examined whether miR-29a was involved in the regulation of HDAC4 and modulation of the profibrogenic phenotype in HSCs. Methods We employed miR-29a transgenic mice (miR-29aTg mice) and wild-type littermates to clarify the role of miR-29a in cholestatic liver fibrosis, using the bile duct-ligation (BDL) mouse model. Primary HSCs from both mice were treated with a miR-29a mimic and antisense inhibitor in order to analyze changes in profibrogenic gene expression and HSC activation using real-time quantitative RT-PCR, immunofluorescence staining, western blotting, and cell proliferation and migration assays. Results After BDL, overexpression of miR-29a decreased collagen-1α1, HDAC4 and activated HSC markers of glial fibrillary acidic protein expression in miR-29aTg mice compared to wild-type littermates. Overexpression of miR-29a and HDAC4 RNA-interference decreased the expression of fibrotic genes, HDAC4 signaling, and HSC migration and proliferation. In contrast, knockdown of miR-29a with an antisense inhibitor increased HDAC4 function, restored HSC migration, and accelerated HSC proliferation. Conclusions Our results indicate that miR-29a ameliorates cholestatic liver fibrosis after BDL, at least partially, by modulating the profibrogenic phenotype of HSCs through inhibition of HDAC4 function.

We present a rare case of a central venous catheter-malposition-induced life-threatening cardiac tamponade as a result of computed tomography (CT) with contrast enhancement in an infant with a ventricular septal defect and pulmonary atresia after a modified Blalock-Taussig shunt. The diagnosis was confirmed by chest radiographs and CT study with catheter perforation through the right atrial wall and extravasation of the contrast medium into the pericardium, leading to cardiac tamponade and subsequent circulatory collapse. Two hours after successful cardiopulmonary resuscitation, the patient gradually resumed normal hemodynamic status.

Emerging evidence indicates that early maternal care permanently modifies the activity of hypothalamic-pituitary-adrenal (HPA) axis and is a critical factor in determining the capacity of the brain to compensate for later encountered insults. The purpose of this study was to determine the role of corticosterone (CORT) in the detrimental effects of neonatal isolation (NI) on seizures. Rats were assigned randomly to the following five groups: (1) control (CONT) rats; (2) NI rats that underwent daily separation from their dams from postnatal day 2 (P2) to P9; (3) status epilepticus (SE) rats, induced by lithium-pilocarpine (Li-Pilo) model at P10; (4) NI plus SE (NIS) rats and (5) NISM rats, a subset of NIS rats receiving metyrapone (100 mg/kg), a CORT synthesis inhibitor, immediately after SE induction. At P10, plasma CORT levels were compared at baseline in CONT and NI rats and in response to Li-Pilo-induced SE among SE, NIS and NISM rats. We evaluated the spatial memory in the Morris water maze at P50 approximately 55, the expression of hippocampal cyclic adenosine monophosphate (cAMP)-responsive element-binding protein phosphorylation at serine-133 (pCREBSer-133) at P55, hippocampal neuronal damage at P80 and seizure threshold at P100. The isolated rats exhibited higher CORT release in response to SE than non-isolated rats, and the NIS rats had greater cognitive deficits and decreased seizure threshold compared to the CONT, NI and SE groups. By contrast, the NISM group, compared to the NIS group, showed a normal CORT response to SE and better spatial memory but no difference in seizure threshold. Compared to the CONT group, the hippocampal pCREBSer-133 level was significantly reduced in all experimental groups (NI, SE, NIS, NISM) with no differences between groups. All rats were free of spontaneous seizures later in life and had no discernible neuronal loss in the hippocampus. Results in this model demonstrate repetitive NI enhances response of plasma CORT to SE, and exacerbates the neurological consequences of neonatal SE. Amelioration of neurological sequelae following reduction of the SE-induced excessive rise in plasma CORT implicates CORT in the pathogenesis of NI increasing the vulnerability to seizures.

The ability of dendritic cells (DCs) to induce immunity or tolerance is related to their state of maturation.1,2 Mature DC express high levels of costimulatory molecules, secrete cytokines including IL-12, and stimulate vigorous T-helper (Th) 1 responses. In contrast, immature DCs (iDCs) express low levels of costimulatory molecules and induce antigen-specific hyporesponsiveness by triggering T-cell apoptosis3 or inducing T regulatory cells.4 It has been well established that intravenous injection of immature donor-derived DCs that are deficient in costimulatory molecules delays the onset of allograft rejection. A limitation to the approach of administering donor-derived iDCs to prevent allograft rejection is that DC propagation either from donor bone marrow (BM) or peripheral blood requires at least 5 to 6 days,5 while decease donor organ transplantation is usually on a semiemergency basis. Thus, an approach using recipient-derived DCs as a means to immunomodulate recipient alloimmunity would be a more feasible approach for such transplants. Maturation of DCs is associated with activation of the nuclear factor (NF)-κB transcription factor, which induces expression of a variety of genes involved in inflammatory responses and costimulatory molecules.6 NF-κB is associated with inhibitor I-κB in the cytoplasm as an inactive complex. Degradation of I-κB allows translocation of the freed NF-κB to the nucleus where it regulates target gene expression by binding to a specific DNA motif. We have constructed a decoy double-stranded oligodeoxynucleotide (ODN) containing consensus NF-κB binding sites that inhibit NF-κB activity. We have also demonstrated that N-FκB ODNs are incorporated efficiently by DCs and specifically inhibit NF-κB DNA-binding capacity.7,8 The NF-κB ODNs selectively suppress costimulatory molecule expression without interfering with major histocompatibility complex (MHC) class I or II expression on DC. This is important, since expression of MHCs on DCs are required in the delivery of tolerogenic signals.5 Modification with the NF-κB ODN renders DCs resistant to maturation, eg, after being stimulated by LPS7 or adenoviral vector transfection.8 In addition, administration of in vitro modified donor-derived NF-κB ODN DCs induces alloreactive T-cell hyporesponsiveness in experimental organ transplant models.7 In this study, we propagated iDCs from recipient C3H mouse BM with GM-CSF whose maturation was arrested by NF-κB ODN. Administration of these iDCs pulsed with donor spleen lysate significantly prolonged B10 allograft survival in C3H recipients in antigen-specific manner. This was associated with induction of specific T-cell hyporesponsiveness and apoptotic death.

Liver abscess is uncommon in children. The purpose of this study is to evaluate the predisposing factors, pathogens, duration of hospitalization, and the managements of liver abscess in children. From 1986 to 2001, fifteen children were admitted to our hospital under the diagnosis of liver abscess. Thirteen cases were older than 8 years old and two were younger than one year old. Fever (15/15, 100%) and abdominal pain (13/15, 87%) were the most common symptoms. Twelve patients (80%) had prolonged fever (fever for 7 days or longer before diagnosis). Eleven (73%) cases were cryptogenic in origin. Most of the microorganisms were obtained solely from cultures of pus. Klebsiella pneumoniae was the most common organism isolated (6/15, 40%). Beside administration of antibiotics, percutaneous catheter drainage (PCD) was performed in 11 patients (73%); only one underwent surgical intervention due to poor response to PCD management. All of our patients were surviving after at least one year follow-up. In conclusion, liver abscess should be suspected in the patients with prolonged fever of unknown origin and abdominal pain. PCD combined with adequate antibiotics were sufficient for therapy of liver abscess in most cases. K. pneumoniae was the most common isolated pathogen in southern Taiwan.

Children with end-stage liver disease have been found to have cognitive deficits. The aim of this study was to examine whether cholestatic jaundice causes spatial deficits in rats and if these cognitive deficits are reversed by biliary drainage. Rats were randomly divided into three groups. In the first group, the bile duct was ligated for 3 weeks (BDL group); in the second group, the proximal bile duct was ligated with a Broviac CV catheter for 2 weeks followed by a tube bilioduodenostomy (TBD group); in the third group, a sham operation was performed (SHAM group). All the surviving rats were assessed for spatial learning and memory (a major cognitive function in rats) by the Morris water maze task about 3 weeks after the first operation. Blood was aspirated by cardiocentesis and assayed for total bilirubin, albumin, ammonia, and hemoglobin levels on the day following the water maze task. During the four consecutive acquisition trial days of the Morris water maze, jaundiced rats (BDL group) had a significant longer latency to escape than the SHAM group (p < 0.05). Rats that underwent biliary decompression for 1 week (TBD group) showed improved status of the spatial deficit, as they required less time to reach the escape platform, approaching the performance of the SHAM group. The BDL group had a significantly higher serum ammonia level, higher bilirubin level, and lower hemoglobin level than the other two groups. After biliary decompression for 1 week, the serum albumin concentration in the TBD group still did not return to the level of the SHAM group. The results of this study suggest that long-term cholestasis results in spatial memory deficits in rats that correlate with anemia and hyperbilirubinemia encephalopathy. Early biliary decompression of obstructive jaundice improves spatial memory deficits, possibly related to the recovery of the serum ammonia and hemoglobin levels.

A 2-year-and-2-month-old boy presented with a tender fist-sized mass in the lower abdomen for 3 days. Turbid urine was also a complaint. His urachal sinus and umbilicus had been removed at the age of 2 months. Abdominal ultrasonography and computed tomography revealed a tumor mass beneath the lower abdominal wall. Total excision of the mass was performed. Microscopic examination showed an abscess located next to a small urachal remnant without stitches or foreign body reaction. To our knowledge, an urachal inflammatory mass mimicking an intra-abdominal tumor after excision of the urachal sinus, especially in children, is very rare. The factors causing such an urachal mass are discussed.

Prediction of the severity of esophageal injury following ingestion of a caustic substance is a challenging problem for clinicians. It was hoped that risk factors for the early prediction of esophageal stricture in such patients could be identified in this study.This study comprises an evaluation of 32 children with esophageal injury due to ingestion of caustic materials. Patients' signs and symptoms as well as laboratory data including leukocyte counts and C-reactive protein level were reviewed.Patients who presented with a greater number of symptoms and signs were inclined to have more severe esophageal injury and stricture. The frequency of symptoms and signs in patients with serious esophageal injury was higher than that in patients with low-grade injury. Patients with severe injury were more significantly associated with the occurrence of stricture. The characteristic of caustic ingestion was associated with esophageal stricture, but not esophageal injury. There was no statistically significant difference in leukocyte counts relative to severity of esophageal injury. The mean of leukocyte counts of patients with esophageal stricture was close to that of patients without esophageal stricture. There was also no statistically significant difference in C-reactive protein values between the 2 groups of patients.Leukocyte counts and C-reactive protein are not useful parameters for predicting the severity of esophageal injury and occurrence of stricture following injury to the esophagus by caustic materials. Alkali ingestion more probably leads to esophageal stricture than acid ingestion. After caustic ingestion, the presence of a greater number of symptoms and signs suggests a more-severe injury, which necessitates more-aggressive management.

Hepatic hemangioendothelioma is rare. We report on hepatic hemangioendotheliomas in 2 young infants, with initial manifestations of respiratory distress and congestive heart failure. Serum alpha-fetoprotein (alphaFP) level was as high as 26,343 microg/l at 14 days old in 1 case, but was only 18 microg/l in the other case. The 2 patients were treated with prednisolone and hepatic artery ligation, respectively, with no residual sequelae after 12 months of follow-up. In this article, the clinical courses of these 2 young infants are reviewed, and the management of infantile hepatic hemangioendothelioma complicated with heart failure is discussed. In our experience, early heart failure caused by infantile hepatic hemangioendothelioma can be well controlled, especially with prednisolone therapy or by hepatic artery ligation. Spontaneous regression has been reported. However, without early recognition and therapeutic intervention, progression to decompensated heart failure may lead to death. Furthermore, it is necessary to differentiate infantile hepatic hemangioendothelioma (IHH) from hepatic malignancies.

Adenocarcinoma of the colon is an unusual disease in patients under 30 years of age, and generally presents as advanced disease because of a lack of awareness of its occurrence, especially in the pediatric age group. The authors report on 2 cases of colon cancer in children less than 17 years old, whose initial presentations were abdominal pain of unclear etiology and non-specific abdominal complaints. No other abnormal laboratory results were found except that 1 patient had anemia. Barium studies revealed the typical colon lesions in both patients, and colonoscopic pathologic examination disclosed mucinous adenocarcinoma. The first patient was rather unusual in that 2 separate tumors were found simultaneously in the large intestine. The therapeutic approach included surgery and adjuvant chemotherapy, but both patients ultimately died due to poor response and early recurrence. Survival obviously depends on the extent of the disease at diagnosis; the earlier the diagnosis is, the better the prognosis will be. Clinical characteristics, diagnosis, and treatment of colon cancer in pediatric patients are discussed.

The purpose of this study was to analyze the characteristics of the clinical presentations, etiologies, diagnoses, and treatment of pediatric pancreatitis in southern Taiwan.Sixty-one patients, ranging in age from 2 to 18 years (mean, 8.8+/-4.8 years old), with diagnoses of pancreatitis were studied from July 1986 through June 2000.Twenty-eight pancreatitis cases resulted from physical trauma, 13 cases of which were from traffic accident (53.8% from motorcycle accident). Other pathogenic factors included systemic diseases (N=9), pancreaticobiliary-tree anomalies (N=7), toxin ingestion or drug use (N=4), Ascaris infection (N=1), and idiopathic (N=12). Symptoms included abdominal pain (N=58), vomiting (N=23), fever (N=18), and jaundice (N=2). Hyperamylasemia was found in 51 children (83.6%). Twenty-seven patients (90.0%) had elevated serum lipase levels (190 U/L) of 30 evaluated. The amylase to creatinine clearance ratio was assayed for 35 cases, of which 28 (80.0%) were elevated (6%). Ultrasonography revealed inflammatory changes of the pancreas in 40 of 51 patients evaluated, while computed tomogram demonstrated evidence of pancreatic inflammation for all 21 patients evaluated. Fifteen cases required surgery, while the other 46 were managed conservatively. One patient died because of acute necrotizing pancreatitis 3 days after L-asparaginase treatment for leukemia. The other patients survived well during long-term follow up.Pancreatitis in children is more common than generally believed. Physical trauma, especially because of motorcycle accidents, was the leading cause of pediatric pancreatitis in southern Taiwan. The mortality rate was low. Only one patient who had undergone chemotherapy with L-asparaginase died of the disease.

Nineteen cases of surgically proven symptomatic pediatric small bowel intussusceptions (SBI) were retrospectively reviewed. Clinical presentations included vomiting (89.5%), abdominal pain and/or irritable crying (89.5%), fever (52.6%), bloody stools (26.3%), palpable abdominal masses (15.8%), hematemesis (10.5%), jaundice (5.3%), and seizures (5.3%). The duration between symptom onset and hospitalization ranged between 20 and 336 hours (average 75.8 hours). Two patients with suspected appendicitis and small bowel obstruction were operated on promptly. Sonograms revealed target lesions (average diameter 2.9 cm) suggestive of intussusception in 13 out of 17 patients, with 10 lesions located in the paraumbilical or left abdominal regions. Barium enemas in 12 of these 13 patients demonstrated no colonic lesions. Diagnosis and surgery were delayed in 16 patients (average delay = 32 hours). The remaining 1 patient with positive sonographic findings underwent early surgery after computed tomographic (CT) confirmation of SBI. Surgery revealed ileoileal intussusceptions in 11 patients, jejunojejunal in 4, jejunoileal in 3, and duodenojejunal in 1. Eight patients had lead points. Bowel complications (ischemia, necrosis, or perforation) occurred in 8 patients. The duration between symptom onset and surgery in patients with bowel complications was significantly longer than for patients without complications (p = 0.0026). In conclusion, delayed diagnosis and surgical treatment in symptomatic pediatric patients with SBI were common, leading to a high rate (42%) of bowel complications. Sonographic demonstration of a 2-3 cm target lesion, especially if paraumbilical or left abdominal, is suggestive of SBI and may obviate the need for a barium enema; however, CT is helpful for confirming SBI. In symptomatic SBI, once diagnosed, early surgical referral is strongly recommended.

Background This study aims to evaluate the outpatient communication skills of medical students via multisource feedback, which may be useful to map future directions in improving physician-patient communication. Methods Family respondents of patients, a nurse, a clinical teacher, and a research assistant evaluated video-recorded medical students’ interactions with outpatients by using multisource feedback questionnaires; students also assessed their own skills. The questionnaire was answered based on the video-recorded interactions between outpatients and the medical students. Results A total of 60 family respondents of the 60 patients completed the questionnaires, 58 (96.7%) of them agreed with the video recording. Two reasons for reluctance were “personal privacy” issues and “simply disagree” with the video recording. The average satisfaction score of the 58 students was 85.1 points, indicating students’ performance was in the category between satisfied and very satisfied. The family respondents were most satisfied with the “teacher”s attitude,“ followed by ”teaching quality”. In contrast, the family respondents were least satisfied with “being open to questions”. Among the 6 assessment domains of communication skills, the students scored highest on “explaining” and lowest on “giving recommendations”. In the detailed assessment by family respondents, the students scored lowest on “asking about life/school burden”. In the multisource analysis, the nurses’ mean score was much higher and the students’ mean self-assessment score was lower than the average scores on all domains. Conclusion The willingness and satisfaction of family respondents were high in this study. Students scored the lowest on giving recommendations to patients. Multisource feedback with video recording is useful in providing more accurate evaluation of students’ communication competence and in identifying the areas of communication that require enhancement.