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Objective: To analysis of risk factors for length of stay in intensive care unit and survival outcome from premature infants with premature rupture of membranes (PROM). Methods: A retrospective study including 189 singleton pregnant women with PPROM at 28– 34 gestational weeks was conducted. Gestational age at delivery, route of delivery, oligohydramnios, maternal age and maternal complications including gestational diabetes, preeclampsia and chorioamnionitis, newborn birth weight, gender, premature retinopathy (ROP), necrotizing enterocolitis (NEC), sepsis, fetal growth retardation (FGR), intracranial hemorrhage (ICH), bronchopulmonary dysplasia (BPD), respiratory distress syndrome (RDS), primary pulmonary hypertension (PPH), congenital cardiac disease (CCD), patent ductus arteriosus (PDA) and use of betamethasone were used to predict neonatal outcomes in terms of length of stay in the ICU and survival. Results: The preeclampsia, low birth weight, ROP, CCD, BPD, and PDA were significant confounders for length of stay in the ICU. Among them, low birth weight was the most powerful confounder for prolongation of the ICU stay (P

Systemic sclerosis (SSc), or scleroderma, is a heterogeneous and complex autoimmune disease characterized by varying degrees of skin and organ fibrosis and obliterative vasculopathy. The disease results in significant morbidity and mortality, and to date, available treatments are limited. Lung involvement is the leading cause of death of patients with SSc. Over the past year, significant advances have been made in our understanding of SSc-associated lung disease, and this review attempts to encapsulate these most recent findings and place them in context.We divide our discussion of the most recent literature into the following: first, clinical aspects of SSc lung management, including classification, imaging, biomarkers, and treatment; second, promising new animal models that may improve our ability to accurately study this disease; and third, studies that advance or change our understanding of SSc lung disease pathogenesis, thereby raising the potential for new targets for therapeutic intervention.Recent advances have resulted in a better understanding of SSc-associated lung disease, the development of new in-vivo models for exploring disease pathogenesis, and the identification of potential novel targets for the development of therapies.

Although advances in surgical technique, immunosuppressive regimens, and medical management have led to improved survival and quality of life after solid organ transplantation, infection continues to represent a major cause of morbidity and mortality in transplant recipients. Immunosuppressive therapy after transplantation compromises cell-mediated immunity in particular, leaving the patient at risk for opportunistic as well as routine community-acquired infections. Mycobacterial infection is a rare but important complication of solid organ transplantation, presenting significant risk to the patient and challenges in terms of treatment. The available literature consists predominantly of case reports and institutional experiences. This article examines both Mycobacterium tuberculosis and nontuberculous mycobacterial infection in the transplant setting.

Acetaminophen toxicity is the most common cause of acute liver failure in the United States and Europe. Although much is known about the metabolism of acetaminophen, many questions remain regarding the pathogenesis of liver injury. In this study, we examined the role of lipopolysaccharide-binding protein (LBP), a protein important in mediating cellular response to lipopolysaccharides, by using LBP wild-type and knockout (KO) mice. We found that LBP KO mice were protected from acetaminophen-induced hepatotoxicity. At 350 mg/kg of acetaminophen, LBP KO mice had significantly less liver injury and necrosis than wild-type mice. Repletion studies in LBP KO mice using an LBP-adenoviral construct resulted in significantly more hepatic injury and necrosis after acetaminophen exposure compared with mice receiving the control adenoviral construct. In conclusion, LBP KO mice are protected from toxicity with a decrease in hepatic necrosis following acetaminophen challenge. This suggests a novel role for LBP in modulating acetaminophen-induced liver injury. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/O270-9139/suppmat/index.html).

The resection of primary and secondary liver tumors has become accepted as the only curative therapy that can be offered to patients with these cancers. Technical advances made over the last two decades have improved the ability of the surgeon to perform these procedures with decreased morbidity. This article reviews hepatic anatomy, the preoperative evaluation of patients and various technical aspects involved in liver resections. The latter includes the role of intraoperative ultrasound and techniques of vascular occlusion and hepatic parenchymal dissection.

Recently, developmental neurobiologists have identified multipotential stem cells in the mature nervous systems of vertebrates. The identification of these progenitor cells, which perdure into adulthood, may have important implications for how we think about brain tumor pathology, as we must now consider the possibility that some tumors may arise from these multipotential precursor cells. Currently, neuropathological classification systems are based primarily upon morphological criteria. While these classification systems provide important information regarding prognosis, they have thus far provided little insight into how, from where, and why any given tumor arises. Even prior to having the knowledge that stem cells are present in the adult central nervous system (CNS), several investigators began to explore the idea that antigenic markers, which have proven invaluable to our understanding of what constitutes the normal repertoire of behaviors and lineages of CNS cells, may provide insights into the basic biology of brain tumors. In the following exegesis, we first highlight two papers that review some of the exciting recent advances in developmental neurobiology and point out what implications this may have on our understanding of brain malignancies. We then present several studies in which the investigators sought to test the hypothesis that the antigenic markers that have proved so useful for the developmental neurobiologist may also prove useful in trying to understand the similarities and differences in various categories of brain tumors. While none of these studies demonstrate definitively that brain tumors can or do arise from the aberrant behavior of CNS stem cells, they do provide enough circumstantial evidence that this may be the case to warrant further serious investigation of this hypothesis.

Background: We previously demonstrated an essential role for lipopolysaccharide binding protein (LBP) in the pulmonary immune response to Gram-negative bacterial infection. LBP knockout mice had significantly higher mortality, greater rates of bacteremia, and higher counts of viable bacteria in their lungs at killing than did wild-type controls. We postulate that systemic LBP gene therapy will reconstitute a protective innate immune response in LBP knockout mice and that overexpression of LBP in wild-type mice may offer a survival advantage. Methods: Twelve-to 16-week-old female C57BL/6 wild-type mice and age-matched LBP knockout mice were given 5 × 109 plaque-forming units of recombinant adenovirus containing either the gene for LBP or the irrelevant control protein β-galactosidase by tail vein injection; 72 hours later; each mouse was administered 1 × 103 colony-forming units of Klebsiella pneumoniae by intratracheal injection. Results: Administration of LBP by systemic gene therapy to LBP knockout mice improved survival from Klebsiella pneumonia to a level equivalent to or better than that in wild-type mice exposed to the same dose of bacteria (36% versus 25%). Wild-type mice given the LBP gene therapy demonstrated increased 7-day survival from Klebsiella pneumonia when compared with controls treated with β-galactosidase (68% versus 30%; p = 0.03). Conclusion: Systemic gene therapy with intravenous adenoviral vector transfer of LBP significantly improves survival in LBP knockout mice. Overexpression of LBP in wild-type mice improves survival from Klebsiella pneumonia. Raising levels of LBP in the setting of Gram-negative pneumonia may be of therapeutic benefit.

Upregulation of CD14 in Kupffer cells has been implicated in the pathogenesis of several forms of liver injury, including alcoholic liver disease. However, it remains unclear whether CD14 mediates lipopolysaccharide (LPS) signaling in this specialized liver macrophage population. In this series of experiments, we determined the role of CD14 in LPS activation of Kupffer cells by using several complementary approaches. First, we isolated Kupffer cells from human livers and studied the effects of anti-CD14 antibodies on LPS activation of these cells. Kupffer cells were incubated with increasing concentrations of LPS in the presence and absence of recombinant human LPS binding protein (LBP). With increasing concentrations of LPS, human Kupffer cell tumor necrosis factor-α (TNF-α) production (a marker for Kupffer cell activation) increased in a dose-dependent manner in the presence and absence of LBP. In the presence of anti-human CD14 antibodies, the production of TNF-α was significantly diminished. Second, we compared LPS activation of Kupffer cells isolated from wild-type and CD14 knockout mice. Kupffer cells from CD14 knockout mice produced significantly less TNF-α in response to the same amount of LPS. Together, these data strongly support a critical role for CD14 in Kupffer cell responses to LPS.

The emergence of multidrug-resistant microbes has serious implications for managing infection and sepsis and has stimulated efforts to develop alternative treatments, such as antimicrobial peptides. The objective of this study was to test a designer peptide, novispirin G10, against multidrug-resistant microorganisms. By two-stage radial diffusion assays, its activity against such organisms compared favorably with that of standard antibiotics and other antimicrobial peptides. It killed bacteria very rapidly, was nonhemolytic, and was relatively noncytotoxic. The peptide induced an immediate, massive efflux of potassium fromPseudomonas aeruginosa, suggesting that it altered the permeability of its inner membrane. The presence of human serum reduced but did not eliminate its activity. We tested the in vivo activity of novispirin G10 in rats with an infected, partial-thickness burn that covered 20% of their total body surface area. The burned area was seeded with 106CFU of a Silvadene-resistantP. aeruginosastrain, and 24 h later a single treatment with 0, 1, 3, or 6 mg of synthetic novispirin G10 (n= 16 at each concentration) per kg was given intradermally. Significant bacterial killing (P< 0.0001) was evident within 4 h in each peptide group compared to controls receiving vehicle. Antimicrobial peptides such as novispirin G10 may provide a useful alternative or adjunct to standard antibiotic agents in treating burns or other wound infections.