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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.

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.

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.

OBJECTIVES:: The aim of this study was to determine the pattern of dog bites seen at the emergency department of a university hospital. The information will be used to plan prevention and enhance management strategies. METHODS:: All patients (younger than 22 years) assessed at the emergency department between January 2003 and December 2004 with a discharge diagnosis of animal bites were identified through the computerized discharge network. RESULTS:: One hundred forty-four incidents of animal bites (82 males and 62 females) occurred over the 2-year period. Eighty-nine percent was due to dog bites. Among the dog bite victims, the mean age was 11.82 years (SD, 6.39 years; range, 0.06-21.83 years). Family dogs were only involved in 15% of cases. The species of dogs were not recognized in three fifths, and attacks provoked in two fifths of victims. Most bites (90%) of bites involved only single anatomical sites. The extremities were commonly involved (right upper limb [23%], left upper limb [16%], right lower limb [35%], left lower limb [20%]). Torso (4%) and genitalia (0.8%) were uncommonly involved. Pain, erythema, bleeding, and bruising were common symptoms, but 60 patients were asymptomatic at presentation. Compared with older patients, children younger than 10 years had a much higher risk of facial injuries (25% vs. 2%, P = 0.0002; odds ratio, 21.8, 95% confidence interval, 2.9-455.9) and were more likely to be triaged as being urgent (P = 0.01). Most attacks were trivial and did not require hospitalization. Antirabies treatment was given in approximately half, analgesics in two fifths, and antibiotics in one fourth. CONCLUSIONS:: In mammalian attacks, canines are most commonly involved. Most injuries are trivial, and the limbs are usually involved. However, younger children are at higher risk of facial injuries. Extent of pain and adverse psychological impacts are typically not documented in the emergency assessment. Language: en

Background— Doxorubicin (DOX) is an important antineoplastic agent. However, the associated cardiotoxicity, possibly mediated by the production of reactive oxygen species, has remained a significant and dose-limiting clinical problem. Our hypothesis is that the hematopoietic/megakaryocytopoietic growth factor thrombopoietin (TPO) protects against DOX-induced cardiotoxicity and might involve antiapoptotic mechanism exerted on cardiomyocytes. Methods and Results— In vitro investigations on H9C2 cell line and spontaneously beating cells of primary, neonatal rat ventricle, as well as an in vivo study in a mouse model of DOX-induced acute cardiomyopathy, were performed. Our results showed that pretreatment with TPO significantly increased viability of DOX-injured H9C2 cells and beating rates of neonatal myocytes, with effects similar to those of dexrazoxane, a clinically approved cardiac protective agent. TPO ameliorated DOX-induced apoptosis of H9C2 cells as demonstrated by assays of annexin V, active caspase-3, and mitochondrial membrane potential. In the mouse model, administration of TPO (12.5 μg/kg IP for 3 alternate days) significantly reduced DOX-induced (20 mg/kg) cardiotoxicity, including low blood cell count, cardiomyocyte lesions (apoptosis, vacuolization, and myofibrillar loss), and animal mortality. Using Doppler echocardiography, we observed increased heart rate, fractional shortening, and cardiac output in animals pretreated with TPO compared with those receiving DOX alone. Conclusions— These data have provided the first evidence that TPO is a protective agent against DOX-induced cardiac injury. We propose to further explore an integrated program, incorporating TPO with other protocols, for treatment of DOX-induced cardiotoxicity and other forms of cardiomyopathy.

Purpose of review To review the current evidence on the use of infection markers for diagnostic evaluation of sepsis in neonates. Recent findings Recent research in immunology has led to the discovery of cell surface antigens, chemokines, cytokines and acute phase proteins that can potentially be used to ‘rule in’ or ‘rule out’ sepsis. The diagnostic utilities of key inflammatory mediators, including CD11b, CD64, interleukin-6 and interleukin-8, are promising and likely to become increasingly used as markers of infection for both diagnostic and prognostic purposes. Summary Serial measurements and use of combinations of markers have been reported to improve sensitivity and negative predictive value of these tests. Current markers are not infallible, however, and do not permit neonatologists to withhold antibiotics in sick infants with suspected infection. Thus, many have emerged as useful indicators for early discontinuation of unnecessary antimicrobial therapy. Some infection markers are also useful for identifying infants with severe infection and adverse prognosis. Advances in flow cytometry have allowed simultaneous measurement of key markers using only minimal blood volume. Judicious selection of a panel of markers with complementary properties could greatly increase the ability of neonatologists to diagnose infection and discern valuable prognostic information.

A preterm infant had persistent Staphylococcus capitis septicemia with 11 consecutive positive blood cultures over a period of 33 days. The clinical evidence suggested that the source of infection probably originated from the gastrointestinal tract. The combination of rifampin and linezolid treatment, together with prolonged stoppage of enteral feeding, successfully terminated the infection. Rifampin and linezolid should be considered as alternative antimicrobial agents when glycopeptides fail to eradicate Gram-positive pathogens from the host.

The clinical findings, plasma viral load, cytokines and chemokines of a 4-month-old infant with severe acute respiratory syndrome (SARS) were assessed at different phases of the disease. Ribavirin failed to inhibit SARS coronavirus (SARS-CoV) replication. One-step real time reverse transcription-polymerase chain reaction for plasma SARS-CoV RNA quantification was useful for early diagnosis and monitoring viremia.