Health informatics for pediatric disaster preparedness planning.

OBJECTIVE: 1. To conduct a review of the role of informatics in pediatric disaster preparedness using all medical databases. 2. To provide recommendations to improve pediatric disaster preparedness by the application of informatics. METHODS: A literature search was conducted using MEDLINE, CINHL and the Cochrane Library using the key words "children" AND "disaster preparedness and disaster" AND "informatics". RESULTS: A total of 314 papers were initially produced by the search and eight that met the selection criteria were included in the review. Four themes emerged: tools for disaster preparedness, education, reunification and planning and response. CONCLUSION: The literature pertaining to informatics and pediatric disaster preparedness is sparse and many gaps still persist. Current disaster preparedness tools focus on the general population and do not specifically address children. The most progress has been achieved in family reunification; however, the recommendations delineated are yet to be completed.

Controversies in the management of necrotizing enterocolitis.

BACKGROUND: Necrotizing enterocolitis (NEC) is the most frequent and lethal disease that affects the gastrointestinal tract of the premature infant. Controversy persists as to the most appropriate management once the diagnosis is confirmed. METHODS: Review of the pertinent medical literature. RESULTS: The incidence of NEC is increasing, but the survival rate is not. Initial management of NEC consists of bowel rest, orogastric decompression, intravenous hydration, and broad-spectrum antibiotics; surgical intervention is typically reserved for infants with advanced disease or evidence of intestinal perforation. There is no consensus in the literature regarding the optimal treatment strategy for patients who require surgical intervention. There exists a lack of randomized trials comparing definitive intestinal resection with or without primary anastomosis, intestinal diversion with limited resection, or peritoneal drainage without resection. CONCLUSION: An individualized approach must be taken to achieve optimum survival for patients with NEC. Isolated perforation, in our opinion, is best managed with resection and enterostomy, whereas pan-intestinal involvement is best managed with proximal diversion alone.

Inhibition of NF-kappaB by IkappaB prevents cytokine-induced NO production and promotes enterocyte apoptosis in vitro.

Nuclear factor-kappaB (N-kappaB) plays a key role in gut inflammation. NF-kappaB up-regulates proinflammatory genes encoding cytokines, adhesion molecules, and inducible nitric oxide synthase (iNOS). However, NF-kappaB has also been shown to up-regulate protective or anti-apoptotic factors. We utilized an adenoviral vector carrying a super-repressor form of the inhibitor of NF-kappaB, IkappaB, to examine the effects of NF-kappaB inhibition on cytokine-induced nitric oxide production and apoptosis in rat small intestinal epithelial cells (IEC-6). Chemical inhibitors of NF-kappaB, including pyrrolidine dithiocarbamate (PDTC), tosyl-lysine-chloromethylketone (TLCK), genistein, and N-acetyl-leu-leu-norleucinal (n-LLnL) were also utilized. Treatment of AdIkappaB-transfected cells with cytomix [1000 U/mL IFN-gamma, 1 nM IL-1beta, and 10 ng/mL tumor necrosis factor alpha (TNFalpha)] or TNFalpha-containing cytokine combinations resulted in inhibition of cytokine-induced nitrite production and a marked increase in apoptosis compared to control cells. Apoptosis occurred independently of nitric oxide (NO) production since exogenous sources of NO did not inhibit apoptosis. Inducible NOS and clAP were down-regulated in AdIkappaB-transfected cells treated with cytomix. TLCK and LLnL treatment also induced apoptosis in cytomix-treated cells, while PDTC and genistein did not. Thus, although NF-kappaB up-regulates various pro-inflammatory genes, it may also have protective or anti-apoptotic effects in enterocytes. NF-kappaB appears necessary for upregulating cIAP in IEC-6 cells upon cytokine exposure.

Early functional outcome in children with pelvic fractures.

BACKGROUND/PURPOSE: Although the mortality, morbidity, and spectrum of associated injuries in children with pelvic fractures have been extensively studied, little is known about the functional outcomes in these patients. The authors examined retrospectively functional independence measurement (FIM) at discharge in children with pelvic fractures to determine how it should influence their management protocol. METHODS: The authors reviewed the records of all patients who sustained pelvic fractures between 1993 and 1998 in the trauma registry of a level I pediatric trauma center. Patients were stratified according to demographics, type of pelvic fracture, functional independence measurement, and discharge disposition. Fractures graded 1, 2, or 3 were defined as stable, whereas grade 4 fractures were deemed unstable. RESULTS: A total of 88 children sustained pelvic fractures. Seventy-four percent had stable fractures, whereas 26% sustained unstable fractures. There was no difference in age or sex between the groups; boys were more commonly injured than girls. Motor vehicle-related crashes accounted for most injuries. The mean injury severity score (ISS) for patients with a stable fracture was 17 +/- 14 and 20 +/- 13 for unstable fractures. There was no difference in overall hospitalization nor intensive care unit stay between the unstable and stable fracture patients. Eighty percent of the patients with unstable and 52% of the patients with stable pelvic fractures were dependent based on locomotion, and similar proportions were seen for the transfer category. CONCLUSIONS: Short-term function appears to be significantly impaired in a high percentage of children with stable and unstable pelvic fractures. Therefore, aggressive rehabilitation should be instituted early in all children with pelvic fractures to achieve optimal functional outcome.

Nitric oxide and intestinal barrier failure.

The systemic inflammatory response syndrome (SIRS) is a leading cause of morbidity and mortality in adults and children. Various proinflammatory mediators have been implicated in the pathogenesis of SIRS; however, their mechanisms of action are poorly defined. Recent evidence suggests that nitric oxide (NO) plays a regulatory role in gut barrier function. Sustained upregulation of NO production in the intestine can lead to intestinal epithelial injury through the formation of peroxynitrite. Peroxynitrite can nitrate mitochondrial proteins and inhibit cellular respiration. The resultant changes in mitochondrial function lead to activation of the caspase cascade, subsequent DNA fragmentation, and enterocyte apoptosis. Enterocyte apoptosis results in a transient "bare area" in the intestinal epithelium where bacteria can attach and then penetrate the lamina propria. Bacteria that successfully escape the immune system may in turn incite a systemic inflammatory response.

Gut-derived mesenteric lymph but not portal blood increases endothelial cell permeability and promotes lung injury after hemorrhagic shock.

OBJECTIVE: To determine whether gut-derived factors leading to organ injury and increased endothelial cell permeability would be present in the mesenteric lymph at higher levels than in the portal blood of rats subjected to hemorrhagic shock. This hypothesis was tested by examining the effect of portal blood plasma and mesenteric lymph on endothelial cell monolayers and the interruption of mesenteric lymph flow on shock-induced lung injury. SUMMARY BACKGROUND DATA: The absence of detectable bacteremia or endotoxemia in the portal blood of trauma victims casts doubt on the role of the gut in the generation of multiple organ failure. Nevertheless, previous experimental work has clearly documented the connection between shock and gut injury as well as the concept of gut-induced sepsis and distant organ failure. One explanation for this apparent paradox would be that gut-derived inflammatory factors are reaching the lung and systemic circulation via the gut lymphatics rather than the portal circulation. METHODS: Human umbilical vein endothelial cell monolayers, grown in two-compartment systems, were exposed to media, sham-shock, or postshock portal blood plasma or lymph, and permeability to rhodamine (10K) was measured. Sprague-Dawley rats were subjected to 90 minutes of sham or actual shock and shock plus lymphatic division (before and after shock). Lung permeability, pulmonary myeloperoxidase levels, alveolar apoptosis, and bronchoalveolar fluid protein content were used to quantitate lung injury. RESULTS: Postshock lymph increased endothelial cell monolayer permeability but not postshock plasma, sham-shock lymph/plasma, or medium. Lymphatic division before hemorrhagic shock prevented shock-induced increases in lung permeability to Evans blue dye and alveolar apoptosis and reduced pulmonary MPO levels. In contrast, division of the mesenteric lymphatics at the end of the shock period but before reperfusion ameliorated but failed to prevent increased lung permeability, alveolar apoptosis, and MPO accumulation. CONCLUSIONS: Gut barrier failure after hemorrhagic shock may be involved in the pathogenesis of shock-induced distant organ injury via gut-derived factors carried in the mesenteric lymph rather than the portal circulation.

Post-hemorrhagic shock mesenteric lymph is cytotoxic to endothelial cells and activates neutrophils.

The goal of these experiments was to test the hypothesis that after a nonlethal episode of hemorrhagic shock, factors carried in the mesenteric lymph would promote endothelial cell injury and activate neutrophils to a greater extent than portal vein plasma. Catheters were placed in the efferent lymphatic duct draining the mesenteric lymph node complex, after which male rats were subjected to sham or actual shock (30 mmHg for 90 min), and lymph was collected. Portal vein plasma was collected from the sham-shock and shocked rats at 6 h post-shock or sham-shock. When the effect of lymph or portal blood plasma was tested on endothelial cell (HUVEC) monolayer permeability, it was found that post-shock lymph, but not post-shock portal vein plasma, increased HUVEC permeability to both 10 kDa and 40 kDa permeability probes. Subsequent experiments documented that only post-shock lymph was cytotoxic to endothelial cells as manifest both by decreased trypan blue dye exclusion and the increased release of Chromium-51 from chromium-loaded endothelial cells. Furthermore post-shock lymph induced a greater increase in neutrophil superoxide formation than pre-shock lymph, pre-shock, or post-shock portal vein plasma. Lastly, neutrophil-mediated endothelial cell injury was potentiated by the presence of post-shock lymph, and the magnitude of HUVEC injury was greater in endothelial cells incubated with post-shock lymph plus neutrophils than in monolayers incubated with post-shock lymph or neutrophils alone. These results suggest that post-shock lymph is cytotoxic to endothelial cells and activates neutrophils. Since the lung is the first organ that is exposed to mesenteric lymph, lung injury after hemorrhagic shock may be mediated by factors contained in mesenteric lymph.

Differential effects of acute hypoxia and endotoxin on the secretion and expression of bone marrow interleukin-1 and interleukin-6.

Hemorrhagic shock induces tissue hypoxia and has been demonstrated to alter the myelopoietic response to bacterial lipopolysaccharide (LPS). Interleukin-1 and interleukin-6 are important mediators of immunologic events after hemorrhagic shock. Bone marrow stroma release inflammatory cytokines, which may play a role in the regulation of myelopoiesis after injury. The aim of this study was to correlate cytokine gene expression with protein release and myelopoiesis by total bone marrow cells. The role of bone marrow stroma after exposure to hypoxia and lipopolysaccharide was also examined. BALB/c mice were designated as normoxia or hypoxia and total bone marrow cells were harvested. Hypoxia mice were exposed to 2 h of 5% O2/95% N2, and then returned to room air. Additional groups of mice were given LPS intraperitoneally. Bone marrow stroma, from BALB/c mice, was similarly designated. Myelopoiesis was assessed by growth of granulocyte-macrophage progenitor cells (CFU-GM). Interleukin-1 and interleukin-6 protein activity was assessed by bioassay. RNA was extracted from both total bone marrow cells and bone marrow stroma. By day 5, LPS alone resulted in a 93% increase in CFU-GM versus normoxia. Hypoxia and LPS exposure significantly decreased CFU-GM on days 1, 3, and 5. LPS alone induced an increase in interleukin-6. At 2, 6, and 24 h, hypoxia blunted interleukin-6 release in response to LPS. Hypoxia alone could not induce interleukin-6. However, hypoxia did induce interleukin-1 mRNA without the release of bioactive protein. In the remainder of groups, interleukin-1 protein levels and mRNA levels were correlated. Bone marrow stroma interleukin-1 and interleukin-6 protein activity was consistently correlated with that of total bone marrow. These data demonstrate that bone marrow cytokine production is differentially regulated by hypoxia. Hypoxia impairs interleukin-6 protein and mRNA in response to LPS, which may play a role in the suppression of myelopoiesis after shock. Also, bone marrow stroma plays an integral role in regulating myelopoiesis.