Resuscitation-induced gut edema and intestinal dysfunction.

BACKGROUND: Mesenteric venous hypertension and subsequent gut edema play a pivotal role in the development of intra-abdominal hypertension. Although gut edema is one cause of intra-abdominal hypertension, its impact on gut function is unknown. The purpose of this study was to create a model of acute hydrostatic gut edema and to evaluate its effect on gut motility and barrier function. METHODS: The first study, group A, evaluated the effect of gut edema on transit over time using 20 mL/kg 0.9% saline. The second study, group B, focused on the 12-hour time period using 80 mL/kg 0.9% saline. Rats were randomized to superior mesenteric vein partial occlusion (venous hypertension) or sham surgery. At 6, 12, and 24 hours, group A underwent intestinal transit and tissue water weight measurements. At 12 hours, group B underwent tissue water, transit, ileal permeability and resistance, lactate and myeloperoxidase activity, and mucosal injury measurements. RESULTS: Venous hypertension with fluid resuscitation caused acute hydrostatic gut edema, delayed intestinal transit, increased mucosal permeability to macromolecules, and decreased tissue resistance over time. Mucosal injury was minimal in mesenteric venous hypertension. CONCLUSION: Acute mesenteric venous hypertension and resuscitation-induced gut edema, in the absence of ischemia/reperfusion injury, is associated with delayed intestinal transit and altered gut barrier function.

A synthetic validity approach to testing differential prediction hypotheses.

A new method is presented for conducting differential prediction analyses that makes it possible to test differential prediction hypotheses with adequate statistical power even when the sample size within a job or a job family is very small. This method, called synthetic differential prediction analysis, represents an application of the logic of synthetic validation to differential prediction analyses. The authors explain this new method and describe its application in a selection-system validation study conducted in a large organization.

Use of single nucleotide polymorphisms (SNP) and real-time polymerase chain reaction for bone marrow engraftment analysis.

Allogeneic bone marrow transplant engraftment assays use polymorphisms in the human genome to determine the relative percentages of donor and recipient cells present in the recipient. We describe a novel posttransplant assay approach using single nucleotide polymorphisms (SNPs), the most common type of polymorphism in humans. Using samples of defined genotype, we used real-time polymerase chain reaction (PCR) and allele-specific fluorescent TaqMan probes to assay a SNP of the cytochrome P450 CYP2C9 gene. Standard curves of chimeric mixes showed a linear relationship between the ratio of two alleles and the ratio of their respective fluorophore emission, except for mixes with a low percentage (< 5%) of the less common allele. We validated the SNP real-time PCR assay by comparing it to Southern hybridization analysis, analyzing DNA mixes in a blinded fashion with both methods. The correlation between the two methods was high. We have produced a statistical model that varies allele frequency to predict how many SNPs would be required to produce a functional SNP panel. Additional development will be necessary to produce such a panel of highly informative SNPs for clinical use. A real-time PCR SNP assay may ultimately provide more accurate quantification and shortened turnaround time compared to current post-engraftment assays.