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We previously demonstrated that microRNA(miR)‐223 is overexpressed in intestinal tissue of infants with necrotizing enterocolitis (NEC). The objective of the current study was to identify the target gene of miR‐223 and to investigate the role of the miR‐223/nuclear factor I‐A (NFIA) axis in cellular functions that underpin the pathophysiology of NEC. The target gene of miR‐223 was identified by in silico target prediction bioinformatics, luciferase assay, and western blotting. We investigated downstream signals of miR‐223 and cellular functions by overexpressing the miRNA in Caco‐2 and FHs74 cells stimulated with lipopolysaccharide or lipoteichoic acid (LTA). NFIA was identified as a target gene of miR‐223. Overexpression of miR‐223 significantly induced MYOM1 and inhibited NFIA and RGN in Caco‐2 cells, while costimulation with LTA decreased expression of GNA11, MYLK, and PRKCZ. Expression levels of GNA11, MYLK, IL‐6, and IL‐8 were increased, and levels of NFIA and RGN were decreased in FHs74 cells. These potential downstream genes were significantly correlated with levels of miR‐223 or NFIA in primary NEC tissues. Overexpression of miR‐223 significantly increased apoptosis of Caco‐2 and FHs74 cells, while proliferation of FHs74 was inhibited. These results suggest that upon binding with NFIA, miR‐223 regulates functional effectors in pathways of apoptosis, cell proliferation, G protein signaling, inflammation, and smooth muscle contraction. The miR‐223/NFIA axis may play an important role in the pathophysiology of NEC by enhancing inflammation and tissue damage., MicroRNA (miR)‐223 is overexpressed in the bowel of infants with necrotizing enterocolitis (NEC). This study investigated the role of miR‐223 in cellular functions that underpin the pathophysiology of NEC. Through identifying direct and downstream targets, and using a gain‐of‐function approach, we demonstrated that the miR‐223/NFIA axis could regulate NEC pathophysiology by interacting with multiple pathways that aggravate inflammation and tissue damage.

The level of microRNA (miR)-431 was found to be markedly up-regulated in intestinal tissue of necrotizing enterocolitis (NEC). The objective of this study was to identify the target gene of miR-431 and to investigate the role of the miR-431-FOXA1 axis in the pathophysiology of NEC. The target gene of miR-431 was identified by in silico target prediction bioinformatics, luciferase assay, and Western blotting. Effects of miR-431 on downstream expression signals, cell proliferation, and apoptosis were investigated by overexpression in Caco-2 cells upon stimulation by LPS or lipoteichoic acid (LTA). FOXA1 was identified as the target gene of miR-431. Overexpression of miR-431 in Caco-2 cells significantly inhibited FOXA1, ESRRG, and HNF4A and activated IL-6, LGR5, NFKB2, PLA2G2A, PRKCZ, and TNF. IL-8 and - 10 were enhanced when costimulated with LPS or LTA. These potential downstream genes were also significantly dysregulated in primary NEC tissues compared with surgical-control tissues. Overexpression of miR-431 significantly decreased proliferation and increased apoptosis of Caco-2 cells. A proposed network of miR-431-FOXA1 interaction with LPS and LTA receptors demonstrates dysregulation of transcription factors, inflammatory mediators, epithelium tight junction regulators, and cell proliferation and apoptosis signals. The miR-431-FOXA1 axis could in part be responsible for the intensification of the inflammatory response in NEC tissues and contribute to the proinflammatory pathophysiology.-Wu, Y. Z., Chan, K. Y. Y., Leung, K. T., Lam, H. S., Tam, Y. H., Lee, K. H., Li, K., Ng, P. C. Dysregulation of miR-431 and target gene FOXA1 in intestinal tissues of infants with necrotizing enterocolitis.

Key Points Specific R4 RGS members are expressed in human HSPCs and regulated by the SDF-1/CXCR4 axis.RGS1/13/16 suppress HSPC engraftment, SDF-1 signaling, and key effectors of stem cell trafficking/maintenance., Visual Abstract, Homing and engraftment of hematopoietic stem/progenitor cells (HSPCs) into the bone marrow (BM) microenvironment are tightly regulated by the chemokine stromal cell–derived factor-1 (SDF-1) and its G-protein–coupled receptor C-X-C motif chemokine receptor 4 (CXCR4), which on engagement with G-protein subunits, trigger downstream migratory signals. Regulators of G-protein signaling (RGS) are GTPase-accelerating protein of the Gα subunit and R4 subfamily members have been implicated in SDF-1–directed trafficking of mature hematopoietic cells, yet their expression and influence on HSPCs remain mostly unknown. Here, we demonstrated that human CD34+ cells expressed multiple R4 RGS genes, of which RGS1, RGS2, RGS13, and RGS16 were significantly upregulated by SDF-1 in a CXCR4-dependent fashion. Forced overexpression of RGS1, RGS13, or RGS16 in CD34+ cells not only inhibited SDF-1–directed migration, calcium mobilization, and phosphorylation of AKT, ERK, and STAT3 in vitro, but also markedly reduced BM engraftment in transplanted NOD/SCID mice. Genome-wide microarray analysis of RGS-overexpressing CD34+ cells detected downregulation of multiple effectors with established roles in stem cell trafficking/maintenance. Convincingly, gain-of-function of selected effectors or ex vivo priming with their ligands significantly enhanced HSPC engraftment. We also constructed an evidence-based network illustrating the overlapping mechanisms of RGS1, RGS13, and RGS16 downstream of SDF-1/CXCR4 and Gαi. This model shows that these RGS members mediate compromised kinase signaling and negative regulation of stem cell functions, complement activation, proteolysis, and cell migration. Collectively, this study uncovers an essential inhibitory role of specific R4 RGS proteins in stem cell engraftment, which could potentially be exploited to develop improved clinical HSPC transplantation protocols.

Objective: The objective of this study is to evaluate the usefulness of fecal microRNA (miR)-223 and miR-451a, as novel noninvasive biomarkers for early diagnosis of necrotizing enterocolitis (NEC) in preterm infants. Methods: Among the top-listed target miRNAs in our previous differential microarray analysis, miR-223 and miR-451a were quantified in a pilot validation case-controlled study (NEC vs. non-NEC/nonsepsis infants; n = 6 in each group). A definitive prospective cohort study (n = 218) further assessed their clinical usefulness as noninvasive and specific diagnostic biomarkers. Fecal calprotectin was quantified in parallel for comparison. Results: Of 43 proven NEC cases in the cohort study, 24 (55.8%) had fecal samples recovered within the first 3 days of clinical presentation. Fecal miRNA-223 (10.5 fold), miR-451a (4.5 fold), and calprotectin (2.1 fold) concentrations were significant higher in NEC compared with the non-NEC group (p < 0.009). Accepting a minimum sensitivity of 0.75, the positive predictive values (PPVs) ranged between 0.19 and 0.20. Combining fecal biomarkers and CRP (Day 1) could marginally increase the PPVs (0.31–0.34) but adversely lowered the sensitivity (0.54–0.63). Conclusions: Although fecal miRNA biomarkers and calprotectin concentrations were significantly higher in the NEC group, the considerable overlapping of concentrations between groups and low recovery of stool specimens within 72 h of clinical presentation rendered fecal noninvasive tests of limited clinical value in guiding diagnosis of NEC during the acute phase. A further study is underway to evaluate their roles in surveillance for predicting high-risk premature infants developing NEC.

Recent advances in molecular and mass screening technologies have paved the way for discovery of novel diagnostic tests and/or biomarkers for accurate identification of specific diseases and organ injuries. However, new diagnostic tests/biomarkers should be subjected to thorough evaluation before introduction into routine clinical practice. This review focuses on the up-to-date methodology in designing and evaluating diagnostic tests/biomarkers, and assessing their clinical utilities for improving health care efficiency, cost-effectiveness and outcomes. In addition to improved diagnostic utilities, future diagnostic tests should be developed in collaboration with our industrial partners and be applicable at the bedside for disease surveillance.

Necrotizing enterocolitis (NEC) remains a devastating surgical emergency with high morbidity and mortality in preterm infants. Slow but steady progress has been made in past years searching for novel biomarkers of NEC, for both surveillance and diagnostic purposes. This review primarily focuses on recent discoveries: clinical applications of different categories of biomarkers for surveillance, early diagnosis, and predicting severity and prognosis; and understanding of pathophysiological mechanisms as a basis to rationalize the search for ‘gut-associated specific biomarkers’ of NEC. An important next step is to collaborate with our industrial partners to develop point-of-care tests, and to discover novel and gut-associated specific biomarkers that can be used for surveillance and early diagnosis of NEC in routine clinical settings.

Endometriosis affects women of reproductive age via unclear immunological mechanism(s). Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of myeloid cells with potent immunosuppressive and angiogenic properties. Here, we found MDSCs significantly increased in the peripheral blood of patients with endometriosis and in the peritoneal cavity of a mouse model of surgically induced endometriosis. Majority of MDSCs were granulocytic, produced ROS, and arginase, and suppressed T-cell proliferation. Depletion of MDSCs by antiGr-1 antibody dramatically suppressed development of endometrial lesions in mice. The chemokines CXCL1, 2, and 5 were expressed at sites of lesion while MDSCs expressed CXCR-2. These CXC-chemokines promoted MDSC migration toward endometriotic implants both in vitro and in vivo. Also, CXCR2-deficient mice show significantly decreased MDSC induction, endometrial lesions, and angiogenesis. Importantly, adoptive transfer of MDSCs into CXCR2-KO mice restored endometriotic growth and angiogenesis. Together, this study demonstrates that MDSCs play a role in the pathogenesis of endometriosis and identifies a novel CXC-chemokine and receptor for the recruitment of MDSCs, thereby providing a potential target for endometriosis treatment.

Preterm infants are at high risk of developing severe sepsis. Circulating hematopoietic stem and progenitor cells (HSPCs; CD45+CD34+) have been suggested to play a vital role in the host immunological defense against invading pathogens. The objectives were to investigate the regulation of circulating HSPCs in preterm infants during infection episodes, and to assess the relationship of CD45+CD34+ cells with immunological mediators and differential leukocyte populations. First, we conducted a cross-sectional case-control study comparing these parameters among infected infants (n = 23), gestational and postnatal age-matched noninfected infants (n = 46), and “healthy” control (CTL) infants (n = 12). Second, we investigated the longitudinal change of CD45+CD34+ cell concentrations in infected infants before, during, and after an infection episode, and compared them with the other two groups. Our cross-sectional results showed that CD45+CD34+ cell count and percentage were significantly reduced in infected infa...

Background: Neonatal sepsis remains an important cause of neonatal morbidity and mortality. Tools to rapidly predict antibiotic resistance in neonatal sepsis would be extremely valuable. Objectives: To develop quantitative polymerase chain reaction (qPCR) primer/probe sets that can rapidly detect antibiotic resistance genes common to a neonatal unit, and to investigate the feasibility of direct detection of antibiotic resistance genes in whole blood of infants with Gram-negative septicaemia without first isolating the organism. Methods: Primer/probe sets were designed to detect genes that produce aminoglycoside-modifying enzymes or extended-spectrum β-lactamase. In phase 1, Gram-negative organisms isolated from neonatal clinical specimens within a 12-month period were analysed by qPCR to detect preselected genes. In phase 2, blood specimens of infants with Gram-negative septicaemia were subjected to qPCR analysis to detect antibiotic resistance genes for comparison against conventional antibiotic resistance profile results. Results: Two primer/probe sets showed promising diagnostic utilities for the prediction of antibiotic resistance; the diagnostic utilities (sensitivity, specificity, positive predictive value and negative predictive value) were 90.9, 96.4, 92.6 and 95.5%, respectively, for AAC3-2 [aac(3ʼ)-IIa/aacC3/aacC2, aac(3ʼ)-IIc/aacC2] to detect gentamicin resistance, and 59.3, 99.3, 94.1 and 92.6%, respectively, for BLA-C1 (blaCTX-M-9, blaCTX-M-14, blaCTX-M-24, blaCTX-M-27) to detect cephalosporin resistance. Twenty-six infants were tested in phase 2, and both gentamicin and cephalosporin resistance patterns were predicted with 100% sensitivity and 100% specificity by AAC3-2 and BLA-C1, respectively. Conclusions: qPCR with appropriately designed primer/probe sets can predict antibiotic resistance directly from neonatal blood, and it can substantially reduce the turnaround time for antibiotic resistance results.

The small intestine is the exclusive site of arginine synthesis in neonates. Low levels of circulating arginine have been associated with the occurrence of necrotizing enterocolitis (NEC) but the mechanism of arginine dysregulation has not been fully elucidated. We aimed to investigate (i) expressional changes of arginine synthesizing and catabolic enzymes in human intestinal tissues of NEC, spontaneous intestinal perforation (SIP) and noninflammatory surgical conditions (Surg-CTL) and to investigate the (ii) mechanisms of arginine dysregulation and enterocyte proliferation upon stimulation by bacterial components, arginine depletion, ARG1 overexpression and nitric oxide (NO) supplementation. Our results showed that expressions of arginine synthesizing enzymes ALDH18A1, ASL, ASS1, CPS1, GLS, OAT and PRODH were significantly decreased in NEC compared with Surg-CTL or SIP tissues. Catabolic enzyme ARG1 was increased (>100-fold) in NEC tissues and histologically demonstrated to be expressed by infiltrating neutrophils. No change in arginine metabolic enzymes was observed between SIP and Surg-CTL tissues. In CaCO2 cells, arginine metabolic enzymes were differentially dysregulated by lipopolysaccharide or lipoteichoic acid. Depletion of arginine reduced cell proliferation and this phenomenon could be partially rescued by NO. Overexpression of ARG1 also reduced enterocyte proliferation. We provided the first expressional profile of arginine metabolic enzymes at the tissue level of NEC. Our findings suggested that arginine homeostasis was severely disturbed and could be triggered by inflammatory responses of enterocytes and infiltrating neutrophils as well as bacterial components. Such reactions could reduce arginine and NO, resulting in mucosal damage. The benefit of arginine supplementation for NEC prophylaxis merits further clinical evaluation.

CD9 has been implicated in cancer progression but its prognostic relevance and therapeutic potential in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) are largely unknown. In a cohort of pediatric BCP-ALL patients, we found that CD9+ cases had a significantly lower 5-year relapse-free survival rate than CD9− cases. Multivariate analysis demonstrated that CD9 positivity independently predicted inferior survival outcomes, and could be applied with established prognostic features, including prednisone response and cytogenetic status, to refine patient stratification. Administration of CD9 antibody substantially suppressed disease progression in NOD/SCID mice xenografted with CD9+ cell lines and primary leukemic blasts from patients with high-risk and refractory BCP-ALL, without compromising hematopoietic stem cell engraftment. Combination of anti-CD9 with conventional chemotherapy further reduced leukemic burden and prolonged animal survival. Mechanistically, CD9 blockade inhibited leukemic cell proliferation, induced G0/G1 cell cycle arrest, activated p38, and enhanced chemotherapeutic agent-induced apoptosis. Further, CD9 physically interacted with integrin very late antigen-4, regulated affinity to vascular cell adhesion molecule-1, and was involved in leukemia–stroma interaction. Collectively, our study established CD9 as a new prognostic marker, validated the preclinical efficacy of CD9 antibody, and laid the foundation for clinical development of CD9-targeted therapy for high-risk and refractory pediatric BCP-ALL.

Objective To discover specific circulating microRNA (miRNA) biomarkers for the early differentiation of necrotizing enterocolitis (NEC) from neonatal sepsis and inflammatory conditions. Study design The study comprised 3 distinct phases: differential microarray analysis to compare plasma miRNA expression profiles of NEC vs sepsis and non-NEC/nonsepsis cases, a case-control study to quantify dysregulated miRNAs as potential specific biomarkers of NEC, and a prospective cohort study to assess the diagnostic usefulness of the best miRNA biomarker(s). Results A distinct miRNA expression profile was observed in the NEC compared with the sepsis and non-NEC/nonsepsis groups. miR-1290, miR-1246, and miR-375 were discovered to be specific biomarkers of NEC in the case-control study. In the cohort study (n = 301), plasma miR-1290 (day 0; >220 copies/µL) provided the greatest diagnostic usefulness for identifying both mild medical and severe surgical NEC cases. Of 20 infants with miR-1290 >650 copies/µL, 15 were diagnosed with NEC. Incorporating C-reactive protein (day 1; >15.8 mg/L) for cases with intermediate levels (220-650 copies/µL) in a 2-stage algorithm further optimized the diagnostic profile with a sensitivity of 0.83, a specificity of 0.96, a positive predictive value of 0.75, and a negative predictive value of 0.98. Importantly, 7 of 36 infants with NEC (19.4%) could be diagnosed 7.8-32.2 hours earlier (median, 13.3 hours) using miR-1290. Conclusions Plasma miR-1290 is a novel and specific biomarker that can effectively differentiate NEC cases from neonatal sepsis. miR-1290 facilitates neonatologists to confidently and timely reach a decision for early transfer of sick infants with NEC from community-based hospitals to tertiary surgical centers.

Neonatal haemophagocytic lymphohistiocytosis (HLH) is a rare but potentially lethal condition. We recently encountered a preterm infant who developed severe HLH associated with maternal adult-onset Still's disease, which to our knowledge has not been previously reported. The infant presented with fever, generalised lymphadenopathy, transient erythematous skin rash, hepatosplenomegaly, ascites, pancytopenia, marked hyperferritinaemia, and hypofibrinogenaemia, which were features similar to maternal presentation during late pregnancy. Whole gene exome sequencing screening for familial HLH (PRF1, STX11, STXBP2, and MUNC13D genes) was negative. We postulated that factors such as auto-antibodies, antigens, or inflammatory mediators transmitted vertically from the mother could have triggered the intense inflammation in the infant. The infant responded promptly to dexamethasone, etoposide, and cyclosporin A, without the need for bone marrow transplantation. Neonatologists should be alerted to the rare diagnosis of HLH in the presence of active maternal diseases, including infection or autoimmune conditions, especially in association with fever, cytopenia, and hepatosplenomegaly.

To provide a comprehensive database of gene regulation and compare differentially regulated molecular networks in human tissues of necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP).Both NEC and SIP are devastating surgical emergencies associated with high morbidity and mortality in preterm infants. Their pathophysiology and molecular mechanisms remain unclear.Differential whole genome microarray analysis was performed on intestinal tissues collected from NEC (n = 15) and SIP (n = 12) infants and compared with tissues collected from surgical-control patients with noninflammatory intestinal conditions (n = 14). Validation of 52 target gene expressions was performed by quantitative polymerase chain reaction. Regulatory networks of significantly affected genes were constructed according to functional pathways.Extensive and significant changes of gene expression were observed in NEC tissues, which comprised multiple pathways of angiogenesis, arginine metabolism, cell adhesion and chemotaxis, extracellular matrix remodeling, hypoxia and oxidative stress, inflammation, and muscle contraction. These dysregulated genes could be networked downstream of key receptors, TLR2, TLR4, and TREM1, and mediated via NF-κB, AP-1, and HIF1A transcription factor pathways, indicating predominant microbial and inflammatory involvement. In contrast, SIP tissues exhibited much milder and less diversified expressional changes, with target genes significantly associated with G-protein-mediated muscle contraction and extracellular matrix remodeling.The molecular evidence suggests that NEC and SIP are likely 2 different diseases caused by distinct etiology and pathophysiology. This first comprehensive database on differential gene expression profiles of human NEC and SIP tissues could lead to development of disease-specific diagnostic and prognostic biomarkers and new therapeutic strategies for improving outcomes.

BACKGROUND Early detection and treatment of infected preterm infants could decrease morbidity and mortality. Neutrophil CD64 has been shown to be an excellent early diagnostic biomarker of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC). We aimed to study whether using CD64 as a daily surveillance biomarker could predict LOS/NEC before clinical manifestation. METHODS We collected 0.1 mL whole blood from very low birth weight (VLBW) infants from day 7 postnatal age until routine daily blood tests were no longer required. Four categories of responses were defined: proven sepsis, clinical sepsis, nonsepsis/non-NEC, and asymptomatic CD64 activation. RESULTS A total of 146 infants were consecutively recruited and 155 episodes of sepsis evaluation were performed. The biomarker screening utility, sensitivity, specificity, positive predictive value, and negative predictive value for surveillance of LOS/NEC using a cutoff of 5655 antibody-PE (phycoerythrin) molecules bound/cell were 89%, 98%, 41%, and 99.8%, respectively. LOS/NEC was detected a mean of 1.5 days before clinical presentation. However, 63 episodes of CD64 activation occurred in asymptomatic infants who would not otherwise have required sepsis evaluations. CONCLUSIONS As a surveillance biomarker, neutrophil CD64 detected LOS/NEC 1.5 days before clinical presentation, but at the expense of performing 41% additional sepsis evaluations. This was mainly attributed to an unexpected group of asymptomatic infants with CD64 activation, who recovered spontaneously and did not require antimicrobial treatment. The latter group has not been previously recognized in VLBW infants and could represent subclinical infection secondary to transient bacterial translocation or mild viral infection.

Background Thrombopoietin (TPO) protects against heart damages by doxorubicin-induced cardiomyopathy in animal models. We aimed to investigate the therapeutic efficacy of TPO for treatment of myocardial infarction (MI) in a rat model and explored the mechanisms in terms of the genome-wide transcriptional profile, TPO downstream protein signals, and bone marrow endothelial progenitor cells (EPCs). Methods Sprague–Dawley rats were divided into 3 groups: Sham-operated, MI (permanent ligation of the left coronary artery) and MI+TPO. Three doses of TPO were administered weekly for 2weeks, and outcomes were assessed at 4 or 8weeks post-injury. Results and conclusions TPO treatment significantly improved left ventricular function, hemodynamic parameters, myocardium morphology, neovascularization and infarct size. MI damage upregulated a large cohort of gene expressions in the infarct border zone, including those functioned in cytoskeleton organization, vascular and matrix remodeling, muscle development, cell cycling and ion transport. TPO treatment significantly reversed these modulations. While phosphorylation of janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3) and protein kinase B (AKT) was modified in MI animals, TPO treatment regulated phosphorylation of STAT3 and extracellular signal-regulated kinases (ERK), and bone morphogenetic protein 1 (BMP1) protein level. TPO also increased EPC colonies in the bone marrow of MI animals. Our data showed that TPO alleviated damages of heart tissues from MI insults, possibly mediated by multi-factorial mechanisms including suppression of over-reacted ventricular remodeling, regulation of TPO downstream signals and mobilization of endothelial progenitor cells. TPO could be developed for treatment of cardiac damages.

Preterm, very low birthweight (VLBW) infants are prone to life-threatening hypotension secondary to hypothalamic-pituitary-adrenal axis immaturity, resulting in adrenocortical insufficiency. Clinical presentations of inotrope-resistant refractory hypotension are usually evident, but interpretation of serum cortisol may pose much difficulty to front-line neonatologists. This review examines the salient pathophysiology of adrenocortical insufficiency in the immediate postnatal period, characterises its endocrinological abnormalities, and describes the typical and variant clinical presentations. Based on existing evidence, a practical scheme is proposed for logical interpretation of circulating cortisol levels and management of inotrope-resistant refractory hypotension in VLBW infants.

Recent reports have advocated treatment of congenital chylothorax with chemical pleurodesis via intrapleural administration of OK-432. Severe complications have not been reported, but recently we have encountered a life-threatening case of massive hemolysis after the procedure. The hemoglobin of the infant decreased from 8.7 to 3.1 g/dl within 48 h, with concomitant severe hyperbilirubinemia (472 μmol/l) requiring exchange transfusion. Frontline neonatologists should be aware of this rare but potentially life-threatening adverse reaction. In addition, it is possible that a longer indwelling time (3.5 vs. 0.5 h) for OK-432 pleurodesis may alter the therapeutic response.

Objectives To assess preferences of health care workers (HCWs) and parents of term and preterm infants to adverse health outcomes, and how perceived surgical mortality influences decision-making. Study design A total of 536 participants (157 HCWs, 201 parents of term infants, and 178 parents of preterm infants) were recruited to take part in a structured interview. Preferences related to treatment of a critically ill preterm infant with necrotizing enterocolitis were measured by health state rank permutation analysis and pivotal risk analysis. Between-group and subgroup comparisons were performed. Results HCWs rank adverse health states less favorably than parents of preterm infants, consistently ranking 2 of the most adverse health states worse than death. Pivotal risk values of HCWs for all health states were consistently the lowest of the 3 groups. High operative mortality was associated uniformly with reduction in pivotal risks for all groups both in favorable and adverse health states. Subgroup analyses revealed significant discrepancies in preferences between fathers and mothers as well as doctors and nurses. Regular religious practice was significantly associated with increased pivotal risks in parental subgroups. Conclusions As discrepancies in health state preferences existed between subgroups (ie, doctors vs nurses, mothers vs fathers) and perceived operative mortality consistently biased parental and HCW health state preferences, we recommend that HCWs should first identify differences regarding patient management before interviewing the parents together. HCWs should be aware of inadvertently biasing parents when discussing the risks and outcomes of surgery in conjunction with the overall long-term prognosis of the underlying condition.

Dexrazoxane (DZR) is a clinically approved agent for preventive treatment of doxorubicin-induced cardiotoxicity. The objective of this study was to investigate the cardioprotective effects of DZR in a rat model of myocardial infarction (MI).Sprague-Dawley rats were randomly divided into four groups: MI (n = 16), MI + DZR (n = 16), SHAM-operated (n = 14) and DZR-only (n = 9). MI animals were subjected to left anterior descending coronary artery ligation. DZR was administered as a single dose at 125 mg/kg intraperitoneally. Four weeks after treatment, cardiac function by echocardiography, infarct size, capillary density in the infarct border zone, bone marrow-derived endothelial progenitor cells (EPCs), and cardiac expression of Bax were measured.Our results demonstrated that MI animals had compromised heart parameters. DZR treatment in MI animals resulted in reduction in infarct size (P = 0.013) and improved cardiac functions in terms of fractional shortening (P = 0.004) and ejection fraction (P = 0.004). The capillary density (P = 0.008) and bone marrow-derived EPCs (P0.05) were higher in the MI + DZR group than those in the untreated MI group. Bax expression was down-regulated in heart tissues of MI + DZR animals (P = 0.043).Our study demonstrated that DZR exerted a cardioprotective effect in the rat model of MI, and the mechanism might be associated with anti-apoptosis and increased neovascularization.

To cite this article: Hon KL, Ching GK, Ng PC, Leung TF. Exploring CCL18, eczema severity and atopy. Pediatric Allergy Immunology 2011; 22: 704–707. Abstract Background: Childhood atopic dermatitis (AD) is a distressing disease associated with pruritus, sleep disturbance, and impaired quality of life. The pathophysiology of AD is complex, and the chemokine CCL18/pulmonary and activation-regulated chemokine (PARC) may be involved. Objective: To evaluate whether CCL18 was associated with disease severity, quality of life, nocturnal scratching, serum eosinophil, and IgE levels. Patients and methods: Patients with AD aged 20 yr or younger were recruited. Disease severity was assessed with the SCORing Atopic Dermatitis (SCORAD) index, quality of life with the Children’s Dermatology Life Quality Index (CDLQI), and nocturnal scratching with a wrist motion monitor. Concentrations of plasma CCL18/PARC, serum total IgE, and eosinophil counts were measured in these patients. Results: One hundred and eight patients with AD (mean [s.d.] age of 10.5 [4.4] yr) were recruited. The mean (s.d.) plasma concentration of CCL18/PARC was 162.2 (129.0) pg/ml, respectively. CCL18/PARC was significantly correlated with objective SCORAD (r = 0.44, p

The present study assessed the relationship between breakfast frequency and measures of obesity in Hong Kong Chinese children aged 9–18 years. A total of 11 570 children (50 % boys) underwent anthropometric measurements and completed a simple self-administered dietary behaviour questionnaire. Their parents completed a questionnaire providing demographic information. Breakfast frequency was assessed by a single question, ‘How many days over the past week did you have breakfast?’ Children were categorised into three groups: skippers (ate breakfast 0–2 times/week); semi-skippers (ate breakfast 3–4 times/week); non-skippers (ate breakfast 5–7 times/week), to assess all associated characteristics. Of the 3644 primary and 7926 secondary school students, 8 % (8·7 % of boys and 6·9 % of girls) and 14 % (14 % of boys and 15 % of girls), respectively, were breakfast skippers. The prevalence of obesity among breakfast skippers, semi-skippers and non-skippers was, respectively, 9·8, 10·6 and 3·8 % (P 0·001) for primary school students and 3·9, 3·1 and 2·4 % (P 0·001) for secondary school students. The 12 % of Hong Kong children aged 9–18 years who skipped breakfast had higher BMI, BMI z-scores and percentage of body fat (PBF) than their counterparts. The dose effects of breakfast frequency (unstandardised regression coefficient, P 0·001) on BMI and PBF were, respectively, − 0·125 kg/m2 and − 0·219 % for boys and − 0·165 kg/m2 and − 0·353 % for girls, adjusting for physical activity per additional breakfast meal per week. Further study is recommended to elucidate whether regular breakfast consumption may have a role in the prevention of childhood obesity.

The key problems faced in developing indwelling catheters are how to incorporate antibacterial agents into the substrate and how to improve the antibacterial effectiveness. In this study, an antibacterial composite coating layer is inversely in situ formed on the silicone substrate by a novel technique involving deposition of an antibacterial agent, solution casting and crosslinking of a silicone resin. The antibacterial particles were strongly bonded to the matrix silicone and evenly dispersed on the coating surface. Moreover, energy-dispersive X-ray analysis revealed the gradient distribution of the antibacterial agent, perpendicular to the composite surface. The co-instantaneous crosslinking within the coating layer and polymer substrate as well as the graded structure formed lead to good adhesion between the two parts. The silicone composite shows a highly efficient antibacterial activity with no cytotoxicity to HL-60 cells. Compared with the commonly used methods of incorporating antibacterial agents into the silicone substrate, such as multiple dip-coating, surface grafting or simple blending, the proposed process is easily operated and is promising for forming a percutaneous or subcutaneous device with the capacity for efficient sterilization in an economical way. Copyright © 2011 Society of Chemical Industry

Purpose of review Functional gastrointestinal dysmotility is a common condition that affects premature infants. Delay in achievement of full enteral nutrition results in dependence on prolonged parenteral nutrition, predisposing to adverse outcomes. Studies in recent years show apparently conflicting results regarding the use of prokinetic agents in preterm infants. This review aims to evaluate these studies to determine whether use of these agents in premature infants is beneficial and justified. Recent findings Randomized controlled trials in recent years have been performed to investigate the effectiveness of erythromycin in the treatment of nonobstructive gastrointestinal dysmotility in preterm infants. Overall, neither low-dose regimes nor prophylactic trials have been shown to be useful. High-dose regimes used as rescue therapy of infants with established gastrointestinal dysmotility have consistently shown clinical benefit. Theoretical risks of prolonged antibiotic use, such as emergence of antibiotic resistance and abnormal intestinal microbiota, have not been fully evaluated. Summary Judicious use of high-dose erythromycin in premature infants as rescue therapy is probably justifiable. Further research in this area is warranted to develop newer prokinetic agents which may improve the safety profile of therapy.

The stromal cell–derived factor-1 (SDF-1)/chemokine C-X-C receptor 4 (CXCR4) axis plays a critical role in homing and engraftment of hematopoietic stem/progenitor cells (HSCs) during bone marrow transplantation. To investigate the transcriptional regulation provided by this axis, we performed the first differential transcriptome profiling of human cord blood CD34+ cells in response to short-term exposure to SDF-1 and identified a panel of genes with putative homing functions. We demonstrated that CD9, a member of the tetraspanin family of proteins, was expressed in CD34+CD38−/lo and CD34+CD38+ cells. CD9 levels were enhanced by SDF-1, which simultaneously down-regulated CXCR4 membrane expression. Using specific inhibitors and activators, we demonstrated that CD9 expression was modulated via CXCR4, G-protein, protein kinase C, phospholipase C, extracellular signal-regulated kinase, and Janus kinase 2 signals. Pretreatment of CD34+ cells with the anti-CD9 monoclonal antibody ALB6 significantly inhibited SDF-1–mediated transendothelial migration and calcium mobilization, whereas adhesion to fibronectin and endothelial cells was enhanced. Pretreatment of CD34+ cells with ALB6 significantly impaired their homing to bone marrow and spleen of sublethally irradiated NOD/SCID (nonobese diabetic/severe combined immune-deficient) mice. Sorted CD34+CD9− cells displayed lower bone marrow homing capacity compared with that of total CD34+ cells. CD9 expression on homed CD34+ cells was significantly up-regulated in vivo. Our results indicate that CD9 might possess specific functions in HSC homing.

Traditional Chinese medicine (TCM) is popular as an alternative medicine in children with atopic dermatitis (AD). A concoction of five herbs in a capsular preparation has been confirmed to be efficacious in improving the quality of life and sparing topical corticosteroid usage. We evaluated the clinical efficacy and tolerability of the same concoction in syrup form.This was a prospective self-controlled trial set in the pediatric dermatology clinic of a teaching hospital. Children aged 4-7 years with moderate-to-severe AD received 20 ml of TCM syrup daily. Clinical parameters and laboratory markers were measured before and at 2 weeks, 7 weeks and 12 weeks of treatment, and at 4 weeks after completion. Disease severity was evaluated by the SCORing Atopic Dermatitis (SCORAD) index and quality of life by the Children's Dermatology Life Quality Index (CDLQI). Blood was obtained for a complete blood count, total IgE, eosinophil count, and biochemical studies prior to and after 3 months of TCM usage.Twenty-two patients participated in the study. There were significant improvements in the objective SCORAD, pruritus and CDLQI scores 4 weeks after study completion. There was no change in sleep score or amount of topical steroid consumption. No biochemical evidence of any adverse drug reaction was observed during the study period. The TCM syrup was generally palatable and well tolerated by the children. Adverse effects were generally mild but two patients with rash withdrew during the study.The palatability means that further evaluations and dosage studies of the concoction will be possible in young children.

Food atopy is important but inadequately studied among children with atopic dermatitis (AD). We evaluated whether any association existed between AD severity, quality of life, total IgE, eosinophil counts, and the number of food items sensitized. Specific IgE of ten common food items was measured for a group of consecutive AD patients (n=85) enrolled during a randomized trial and correlated the findings with eczema severity. Twenty-four patients (28%) were negative for any of the ten common food items. The most commonly sensitized foods were shrimp (54%), egg white (43%), wheat (42%), and peanut (41%). Atopy to beef as a protein and orange as a fruit were least common among the food items studied, even among patients positive for 8-9 IgE items. Patients with severe AD (objective SCORAD>40) were more likely to be positive for at least one of the food items (Yates corrected p=0.024 for ≥1 food-specific IgE in severe vs. moderate AD, OR 3.42 and 95% CI 1.15-10.32); and for at least seven of the food items (p=0.001 for ≥7 food-specific IgE vs. nil with OR 11.67 and 95% CI 2.29-67.77), respectively. The Spearman coefficients between the number of positive food-specific IgE and total SCORAD, objective SCORAD, area of AD involvement, Children's Dermatology Life Quality Index (CDLQI), total IgE levels, and eosinophil counts were 0.42 (p

Objectives To investigate if morbidity in young children admitted to a pediatric intensive care unit (PICU with a laboratory proven diagnosis of influenza and parainfluenza infection) had increased. Methods Retrospective study from January 2003 through December 2009 was carried out. Every child in the PICU with a laboratory-confirmed influenza or parainfluenza infection was included. Results 18 influenza (influenza A = 13 and influenza B = 5) and 17 parainfluenza admissions were identified over the 7-year period. Parainfluenza type 3 (n = 9) was the commonest subtype of parainfluenza infection. The median age of children admitted with influenza was higher than parainfluenza (4.5 vs 1.7 years, p = 0.044). Admissions associated with proven influenza and parainfluenza infections accounted for 2% of PICU annual admissions. There was only one death in 2003. 51% of these patients required ventilatory support, 45% received systemic corticosteroids, and 91% received initial broad spectrum antibiotic coverage. Bacterial co-infections were identified in 25% of these patients. The incidence of influenza admissions had not increased significantly in 2009 (H1N1 pandemic) when compared with 2003 (SARS epidemic) (p = 0.3). There were only two PICU cases of pandemic H1N1 in 2009 and both survived. The annual incidence of severe PICU cases of influenza and parainfluenza were 0.94 and 0.88 per 100,000 children per annum, respectively. Conclusions Pandemic H1N1, influenza and parainfluenza viruses may be associated with significant childhood morbidity and PICU admissions.

Preterm infants are highly susceptible to life-threatening infections that are clinically difficult to detect, such as late-onset septicemia and necrotizing enterocolitis (NEC). Here, we used a proteomic approach to identify biomarkers for diagnosis of these devastating conditions. In a case-control study comprising 77 sepsis/NEC and 77 nonsepsis cases (10 in each group being monitored longitudinally), plasma samples collected at clinical presentation were assessed in the biomarker discovery and independent validation phases. We validated the discovered biomarkers in a prospective cohort study with 104 consecutively suspected sepsis/NEC episodes. Proapolipoprotein CII (Pro-apoC2) and a des-arginine variant of serum amyloid A (SAA) were identified as the most promising biomarkers. The ApoSAA score computed from plasma apoC2 and SAA concentrations was effective in identifying sepsis/NEC cases in the case-control and cohort studies. Stratification of infants into different risk categories by the ApoSAA score enabled neonatologists to withhold treatment in 45% and enact early stoppage of antibiotics in 16% of nonsepsis infants. The negative predictive value of this antibiotic policy was 100%. The ApoSAA score could potentially allow early and accurate diagnosis of sepsis/NEC. Upon confirmation by further multicenter trials, the score would facilitate rational prescription of antibiotics and target infants who require urgent treatment.

The incidence of eczema has been increasing in developed countries. Environmental and hygiene factors have been incriminated. Although air and food pollution with heavy metals have been considered as possible culprits, these factors have never been investigated in Hong Kong. To evaluate if quality of life and eczema severity are associated with abnormal serum levels of six common heavy metals, namely, cadmium, lead, mercury, selenium, copper and zinc. Serum or whole blood was taken for measurement of six heavy metals from patients referred to the pediatric dermatology clinic. Eczema severity (SCORAD and NESS) and quality of life (CDLQI) were recorded. A total of 110 patients with eczema and 41 patients with miscellaneous skin conditions were recruited. Serum levels of the six heavy metals were generally within the upper limits of local reference ranges. Zinc levels were below the lower reference limit of 9.4 mum in 66 patients with eczema (60%) and 22 non-eczema patients (53%). Forty-four patients with eczema (40%) and 24 (58%) in non-eczema group had low copper levels. In eczema patients, lead levels were generally within normal limits but their levels were positively correlated with poor quality of life (CDLQI: r = 0.22 and p < 0.05), disease severity (objective SCORAD: r = 0.33 and p < 0.005; NESS: 0.20, p < 0.05), eosinophil count and log-transformed IgE. Copper/zinc ratio also correlated with NESS and CDLQI and was generally higher than non-eczema skin diseases. Our findings help reassure parents that levels of heavy metals generally do not exceed the local reference ranges for toxicity. However, lead levels have significant correlations with disease severity, quality of life and atopy. Low zinc and copper levels are commonly found in pediatric skin diseases and their significance needs to be determined.

We report early MR changes that occurred on day 3 and 5 weeks after the accidental cyanide ingestion in a child. As the toxicity of cyanide is based on the inactivation of cytochrome oxidase, a terminal enzyme in the cellular respiration chain, cerebral structures with the highest oxygen requirement, such as basal ganglia, cerebral cortex, and sensorimotor cortex are most commonly affected. At an early phase, the toxic changes can be visible as pronounced restricted diffusion on DWI and onset of lactate peak on MR spectroscopy when the altered signal intensity on conventional T2W and T1W sequences is still lacking. Classical T2-weighted hyperintensities develop and general reduction in fractional anisotropy (FA) is evident on diffusion tensor imaging (DTI) in the follow up study. The FA is most significantly reduced in periventricular white matter with classical T2 hyperintensities. These changes correlated well with his clinical evolution into dystonic cerebral palsy during hospitalization.

Summary Background. Atopic eczema (AE) is characterized by reduced skin hydration (SH) and impaired integrity of the skin. Proper emollient usage is an important facet of AE management and patients are encouraged to use emollients liberally. Aim. To evaluate whether the amount of emollient and skin cleanser used correlates with eczema severity, SH or transepidermal water loss (TEWL), and whether liberal usage alters disease severity, SH and TEWL. Methods. We studied SH and TEWL at three common measurement sites on the forearm (antecubital flexure, 20 mm below the antecubital flexure, mid-forearm) and determined the SCORing Atopic Dermatitis (SCORAD) score, Nottingham Eczema Severity Score (NESS), Children’s Dermatology Life Quality Index (CDLQI) and the amount of emollient and cleanser usage over a 2-week period in consecutive new patients seen at the paediatric skin clinic of a teaching hospital. Results. In total, 48 subjects and 19 controls were recruited. Patients with AE had significantly higher TEWL and lower SH in the studied sites. Emollient and cleanser usage was significantly higher (P = 0.001 and P = 0.041, respectively) in patients with AE than in controls. The amount of emollient usage was correlated with NESS, SCORAD, CDLQI, TEWL and mid-forearm SH. No such correlation was found with cleanser usage. Regardless of SCORAD, prescribing 130 g/m2/week of emollient met the requirement of 95.8% of patients, and 73 g/m2/week met that of 85.4%; for the cleanser, prescribing 136 g/m2/week met the requirement of 91.7% of patients. Although skin dryness and SH were improved, there was no significant improvement in SCORAD or TEWL after 2 weeks. In terms of global acceptability of treatment, three-quarters of patients with AE and controls rated the combination of cream and cleanser as ‘good’ or ‘very good’. Conclusions. Adequate amounts of emollient and bathing cleanser should be prescribed to patients with AE. These amounts can be conveniently estimated based on body surface area instead of the less readily available tools for disease severity, degree of SH or skin integrity. However, liberal usage of emollients and bathing cleanser alone does not seem to alter disease severity or TEWL within 2 weeks, implying that additional treatments are necessary to manage AE.

The natural history of mild childhood obstructive sleep apnoea (OSA) was examined and factors associated with disease progression were identified.Subjects were recruited from an epidemiological study which examined the prevalence of OSA in Chinese children aged 6-13 years. The first 56 consecutive children identified with mild OSA (apnoea-hypopnoea index 1-5) were invited for a repeat assessment 2 years after the diagnosis.45 children participated in the follow-up study, in 13 of whom (29%) the OSA was found to have worsened. Compared with those in whom OSA had not worsened, the worsened OSA group had a greater increase in waist circumference, a higher prevalence of large tonsils (occupyingor =50% of the airway) at both baseline and follow-up, and a higher prevalence of habitual snoring at both baseline and follow-up. The presence of large tonsils had a positive predictive value of 53% and a negative predictive value of 83% for worsening OSA over a 2-year period. Multivariate linear regression analysis showed that the change in obstructive apnoea-hypopnoea index was associated with age at baseline (beta (SE) = -0.92 (0.34), p = 0.009), gender (male = 1; female = 0) (beta (SE) = 4.69 (1.29), p0.001), presence of large tonsils at baseline (beta (SE) = 4.36 (1.24), p = 0.001), change in waist circumference (beta (SE) = 0.30 (0.09), p = 0.002) and persistently large tonsils (beta (SE) = 5.69 (1.36), p0.001) over the 2-year period.Mild OSA in the majority of children does not resolve spontaneously. Subjects with tonsillar hypertrophy, especially boys, should be closely monitored to allow early detection of worsening OSA. Weight control should be stressed in the management of childhood OSA.

To evaluate the usefulness of the Gram-specific probe-based quantitative polymerase chain reaction test for rapid detection and differentiation of Gram-negative and Gram-positive bacterial bloodstream infection in preterm infants.Cross-sectional study.University-affiliated Level III neonatal intensive care unit.Preterm infants with clinical features suggestive of late-onset infection.None.In addition to the full sepsis screen, 0.5 mL of EDTA blood was collected aseptically for Gram-specific quantitative polymerase chain reaction evaluation. The results were analyzed with respect to outcomes of bacterial culture in blood and other body fluids, including peritoneal and cerebrospinal fluids. The diagnostic utilities of the quantitative polymerase chain reaction were determined. A total of 218 suspected infection episodes were investigated, of which 42 episodes were culture positive and 176 were culture negative. For Gram-negative infection, the quantitative polymerase chain reaction test correctly identified 19 of 22 episodes, and the sensitivity and specificity were 86.4% and 99.0%, respectively. For Gram-positive infection, the test correctly identified 14/19 episodes, and the sensitivity and specificity were 73.7% and 98.5%. The remaining one episode was Candida albicans septicemia. None of the episodes with positive quantitative polymerase chain reaction test were classified into the wrong Gram stain category. More importantly, despite negative blood culture in five infants suffering from intra-abdominal sepsis (peritonitis [n = 4] and hepatosplenic abscess [n = 1]), the quantitative polymerase chain reaction test could detect the Gram-specific category of causative organisms in blood.The Gram-specific quantitative polymerase chain reaction test is reliable and highly specific for rapid identification and differentiation of Gram-negative and Gram-positive bloodstream and intra-abdominal infections. The result could be made available within 5 hrs after the specimen reaches the laboratory. A positive test is able to "rule in" bacterial bloodstream infection before blood culture results become available, and serves as a guide to predict the virulence of the causative organism according to its Gram-specific category so that critical patients can be targeted for intensive treatment.

Background: Recent studies suggest that a low antioxidant level in preterm infants may predispose them to increased oxidative stress and results in hyperbilirubinemia, whereas glucose-6-phosphate dehydrogenase (G6PD) activity was found to be higher in preterm infants than in term infants. Objectives: To evaluate (1) the oxidative effect of α-naphthol on preterm and term red blood cells, and (2) the relationship between G6PD activity and the gestational age of these infants. Methods: G6PD activities were determined in preterm and term infants by a standard diagnostic method. Whole blood samples were incubated with α-naphthol for 2 h and their pre- and post-challenged reduced glutathione (GSH) levels were quantified. Results: The mean G6PD activity in preterm infants (n = 113; 13.52 ± 0.19 U/g Hb; gestational age 30.67 ± 0.28 weeks) was significantly higher than that in term infants (n = 100; 12.36 ± 0.16 U/g Hb; gestational age 39.82 ± 0.14 weeks; p < 0.001). A significantly negative correlation was demonstrated between gestational age and G6PD activity (r = –0.34, p < 0.001). GSH levels of preterm and term subjects were similar at baseline, but were significantly decreased upon challenge with α-naphthol (p < 0.001). The percentage reduction in GSH levels was similar in the various gestational age groups. Conclusions: Our data show that G6PD activities had a negative correlation with gestational age of G6PD-normal infants. The similar response of preterm and term erythrocytes to an α-naphthol challenge indicates the manifestation of an active anti-oxidative pathway mediated by cellular GSH.

Milk intolerance due to functional gastrointestinal (GI) dysmotility is a common problem in preterm infants. In the past decade, erythromycin has been used for its motilinomimetric effect to facilitate enteral feeding in preterm infants. Although earlier studies suggested that erythromycin is an effective prokinetic agent, recent randomized control trials (RCTs) reveal conflicting findings. This review assesses the evidence from all RCTs performed to date on erythromycin for preterm infants. The results suggest that oral erythromycin administered in intermediate or high doses as a rescue treatment is associated with a shorter time to attain full enteral feeding and decrease in the duration of requirement for parenteral nutrition. More importantly, the outcome study further indicates that oral erythromycin can reduce the incidence of parenteral nutrition-associated cholestasis by almost 50% and decreases the incidence of recurrent septicemia. None of the RCTs reported any sinister adverse effects, in particular, hypertrophic infantile pyloric stenosis or fatal cardiac arrhythmia. Nonetheless, as long-term outcomes have not been fully evaluated, neonatologists should use this treatment cautiously and selectively in preterm infants with moderately severe GI dysmotility.

We report a case of neonatal subdural empyema caused by Mycoplasma hominis. The infant sustained severe birth-related eye injury and subsequently developed multiple subdural empyemata. This report illustrates the clinical presentation of this unusual infection and the crucial role of neurosurgical intervention and specific antimicrobial therapy for its successful management.

Glucose-6-phosphate dehydrogenase (G6PD)-deficient subjects are susceptible to chemical-induced oxidative haemolysis. Little is known concerning the haemolytic properties of Chinese herbal medicine on G6PD-deficient subjects. Our objective was to investigate the pro-oxidative effect of 18 commonly used Chinese herbal medicine (CHM) on human G6PD-deficient red blood cells. G6PD-deficient (n=10) and normal (n=10) whole blood samples were incubated with water extracts of CHM. The resulting levels of reduced glutathione (GSH) and methaemoglobin (MetHb) were determined by biochemical assays. Rhizoma Coptidis significantly reduced GSH level by 48.9+/-5.4% (at 1 mg/mL) in the G6PD-deficient erythrocytes (P

Introduction: Childhood poisonings are common, but usually trivial, and infrequently necessitate intensive care unit (ICU) admissions. Methods: A retrospective record review was conducted to analyze the pattern of severe poisoning-associated ICU admissions at a teaching hospital between May 2002 and December 2007. Results: Six cases (4 boys and 2 girls, aged 2 months to 11 years) of drug poisoning-associated ICU admissions were identified. Methadone was the culprit in 3 boys and 1 girl, resulting in respiratory failure, depressed conscious state and pinpoint pupils. As relevant exposure history was not immediately apparent, diagnosis at the emergency department was only made correctly in 2 patients. Phenobarbitone overdose occurred in 1 girl with past history of phenobarbitone overdose as a clue. She was also considered to have pinpoint pupils that were unresponsive to naloxone. Features consistent with cholinergic toxidrome, including small pupils, and increased secretion occurred in an infant fed with milk prepared with an herbal broth suspected to have been adulterated with a pesticide. Atropine as an antidote was used when the child was in the pediatric ICU. All children made an uneventful recovery following their short ICU stay. Conclusions: Life-threatening poisonings requiring ICU support can pose diagnostic difficulties and challenges to frontline medical officers at the emergency department. Children from all age groups can be affected. Prompt diagnosis is based on relevant history, careful clinical examination and a high index of suspicion in patients known to be at risk. The pupillary size and its reaction following treatment serves as an important diagnostic clue.

To determine the intraocular pressure (IOP) profile during and after systemic dexamethasone treatment in preterm very low birth weight (VLBW;1500 g) infants.A cohort study at a university-affiliated tertiary neonatal center.Twenty-seven VLBW infants who received a 3-week dose-tapering course of systemic dexamethasone for treatment of bronchopulmonary dysplasia were consecutively enrolled over a period of 32 months.Intraocular pressure was assessed using a handheld tonometer immediately before (week 0), during (weeks 1 and 3), and after (weeks 5, 7, and 9) commencement of the dexamethasone course. The mixed-effects models were used to evaluate the longitudinal IOP measurements at different time points.To assess the magnitude and duration of increase in IOP during systemic corticosteroid treatment.The IOP at week 1, while the infants were receiving the maximum dose of dexamethasone (0.6 mg/kg/day), was significantly higher than (1) the pretreatment IOP at week 0 (mean [+/- standard deviation]: 19.7 [+/-3.7] vs. 16.4 [+/-3.7] mmHg, respectively) (P0.0001), (2) the IOP when the infants were receiving the minimum dose of dexamethasone (0.15 mg/kg/day) at week 3 (19.7 [+/-3.7] vs. 15.8 [+/-4.3] mmHg) (P0.0001), and (3) the IOP after the dexamethasone course had been stopped between week 5 and week 9 (19.7 [+/-3.7] vs. 16.0 [+/-4.0], 15.3 [+/-3.5], and 14.5 [+/-3.3] mmHg for weeks 5, 7, and 9, respectively) (P0.0001 for all comparisons). In contrast, there was no significant difference between the pretreatment IOP (week 0) and IOP at week 3, 5, 7, or 9 (P = 0.07-0.62) and in the IOP between week 3 and week 5, 7, or 9 (P = 0.27-0.75).The use of a dose-tapering regime of dexamethasone is associated with transient increase of IOP. As IOP was significantly raised during the high-dose but not the low-dose treatment period, we speculate that the physiologic or stress dose of corticosteroids commonly advocated for treatment of serious neonatal conditions should be safe and unlikely to cause significant ocular hypertension in preterm infants.

Hair loss (alopecia) is a relatively common problem in childhood and the underlying pathophysiology and manifestations are diverse. We report four cases of hair loss with unusual distributions and discuss the outcome of their management. One child had alopecia with unilateral loss of hair over the eyebrow. He received topical corticosteroids and tacrolimus and his condition resolved. A girl had scalp alopecia which evolved to alopecia universalis. The mother and the child were non-compliant with treatment. A boy had alopecia totalis not responsive to Western or alternative treatment. The fourth child had trichotillomania and bizarre loss of scalp hair. Mother and child received psychological counselling and the child's hair loss improved. It is important to differentiate between alopecia and trichotillomania as the management is very different. Diagnosis and treatment are based on clinical assessment, evaluation of coexisting psychosocial factors and exclusion of autoimmune and other underlying disorders. In alopecia totalis or universalis, alternative therapy is often sought and tried for prolonged periods but efficacy has remained unproven. These cases serve to illustrate the principles of management of children with unusual patterns of hair loss.