Faculty Bibliography

BACKGROUND: Postoperative ileus (POI) can worsen outcomes, increase cost, and prolong hospitalization. An objective marker could help identify POI patients who should not be prematurely fed. We developed a disposable, non-invasive acoustic gastro-intestinal surveillance (AGIS) biosensor. We tested whether AGIS can distinguish healthy controls from patients recovering from abdominal surgery. STUDY DESIGN: AGIS is a disposable plastic device embedded with a microphone that adheres to the abdominal wall and connects to a computer that measures acoustic event rates. We compared intestinal rates of healthy subjects using AGIS for 60 min after a standardized meal to recordings of two postoperative groups: (1) patients tolerating standardized feeding and (2) POI patients. We compared intestinal rates among groups using ANOVA and t tests. RESULTS: There were 8 healthy controls, 7 patients tolerating feeding, and 25 with POI; mean intestinal rates were 0.14, 0.03, and 0.016 events per second, respectively (ANOVA p < 0.001). AGIS separated patients from controls with 100 % sensitivity and 97 % specificity. Among patients, rates were higher in fed versus POI subjects (p = 0.017). CONCLUSION: Non-invasive, abdominal acoustic monitoring distinguishes POI from non-POI subjects. Future research will test whether AGIS can identify patients at risk for development of POI and assist with postoperative feeding decisions.

Angiotensin II causes cardiovascular injury in part by aldosterone-induced mineralocorticoid receptor activation, and it can also activate the mineralocorticoid receptor in the absence of aldosterone in vitro. Here we tested whether endogenous aldosterone contributes to angiotensin II/salt-induced cardiac, vascular, and renal injury by the mineralocorticoid receptor. Aldosterone synthase knockout mice and wild-type littermates were treated with angiotensin II or vehicle plus the mineralocorticoid receptor antagonist spironolactone or regular diet while drinking 0.9% saline. Angiotensin II/salt caused hypertension in both the knockout and wild-type mice, an effect significantly blunted in the knockout mice. Either genetic aldosterone deficiency or mineralocorticoid receptor antagonism reduced cardiac hypertrophy, aortic remodeling, and albuminuria, as well as cardiac, aortic, and renal plasminogen activator inhibitor-1 mRNA expression during angiotensin II treatment. Mineralocorticoid receptor antagonism reduced angiotensin II/salt-induced glomerular hypertrophy, but aldosterone deficiency did not. Combined mineralocorticoid receptor antagonism and aldosterone deficiency reduced blood urea nitrogen and restored nephrin immunoreactivity. Angiotensin II/salt also promoted glomerular injury through the mineralocorticoid receptor in the absence of aldosterone. Thus, mineralocorticoid antagonism may have protective effects in the kidney beyond aldosterone synthase inhibition.

BACKGROUND: Effective collaboration and teamwork is essential to providing safe hospital care. The objective of this study was to assess the effect of an intervention designed to improve interdisciplinary collaboration and lower the rate of adverse events (AEs). METHODS: The study was a controlled trial of an intervention, Structured Inter-Disciplinary Rounds, implemented in 1 of 2 similar medical teaching units in a tertiary care academic hospital. The intervention combined a structured format for communication with a forum for regular interdisciplinary meetings. We conducted a retrospective medical record review evaluating 370 randomly selected patients admitted to the intervention and control units (n = 185 each) in the 24 weeks after and 185 admitted to the intervention unit in the 24 weeks before the implementation of Structured Inter-Disciplinary Rounds (N = 555). Medical records were screened for AEs. Two hospitalists confirmed the presence of AEs and assessed their preventability and severity in a masked fashion. We used multivariable Poisson regression models to compare the adjusted incidence of AEs in the intervention unit to that in concurrent and historic control units. RESULTS: The rate of AEs was 3.9 per 100 patient-days for the intervention unit compared with 7.2 and 7.7 per 100 patient-days, respectively, for the concurrent and historic control units (adjusted rate ratio, 0.54; P = .005; and 0.51; P = .001). The rate of preventable AEs was 0.9 per 100 patient-days for the intervention unit compared with 2.8 and 2.1 per 100 patient-days for the concurrent and historic control units (adjusted rate ratio, 0.27; P = .002; and 0.37; P = .02). The low number of AEs rated as serious or life-threatening precluded statistical analysis for differences in rates of events classified as serious or serious and preventable. CONCLUSION: Structured Inter-Disciplinary Rounds significantly reduced the adjusted rate of AEs in a medical teaching unit.

Structure-mechanism relationships are key determinants of host defense peptide efficacy. These relationships are influenced by anatomic, physiologic and microbiologic contexts. Structure-mechanism correlates were assessed for the synthetic peptide RP-1, modeled on microbicidal domains of platelet kinocidins. Antimicrobial efficacies and mechanisms of action against susceptible ((S)) or resistant ((R)) Salmonella typhimurium (ST), Staphylococcus aureus (SA), and Candida albicans (CA) strain pairs were studied at pH 7.5 and 5.5. Although RP-1 was active against all study organisms, it exhibited greater efficacy against bacteria at pH 7.5, but greater efficacy against CA at pH 5.5. RP-1 de-energized SA and CA, but caused hyperpolarization of ST in both pH conditions. However, RP-1 permeabilized ST(S) and CA strains at both pH, whereas permeabilization was modest for ST(R) or SA strain at either pH. Biochemical analysis, molecular modeling, and FTIR spectroscopy data revealed that RP-1 has indistinguishable net charge and backbone trajectories at pH 5.5 and 7.5. Yet, concordant with organism-specific efficacy, surface plasmon resonance, and FTIR, molecular dynamics revealed modest helical order increases but greater RP-1 avidity and penetration of bacterial than eukaryotic lipid systems, particularly at pH 7.5. The present findings suggest that pH- and target-cell lipid contexts influence selective antimicrobial efficacy and mechanisms of RP-1 action. These findings offer new insights into selective antimicrobial efficacy and context-specificity of antimicrobial peptides in host defense, and support design strategies for potent anti-infective peptides with minimal concomitant cytotoxicity.

Abdominal obesity is associated with metabolic risk factors for coronary heart disease (CHD). Although we previously found that using liposuction surgery to remove abdominal subcutaneous adipose tissue (SAT) did not result in metabolic benefits, it is possible that postoperative inflammation masked the beneficial effects. Therefore, this study provides a long-term evaluation of a cohort of subjects from our original study. Body composition and metabolic risk factors for CHD, including oral glucose tolerance, insulin resistance, plasma lipid profile, and blood pressure were evaluated in seven obese (39 +/- 2 kg/m(2)) women before and at 10, 27, and 84-208 weeks after large-volume liposuction. Liposuction surgery removed 9.4 +/- 1.8 kg of body fat (16 +/- 2% of total fat mass; 6.1 +/- 1.4 kg decrease in body weight), primarily from abdominal SAT; body composition and weight remained the same from 10 through 84-208 weeks. Metabolic endpoints (oral glucose tolerance, homeostasis model assessment of insulin resistance, blood pressure and plasma triglyceride (TG), high-density lipoprotein (HDL)-cholesterol, and low-density lipoprotein (LDL)-cholesterol concentrations) obtained at 10 through 208 weeks were not different from baseline and did not change over time. These data demonstrate that removal of a large amount of abdominal SAT by using liposuction does not improve CHD metabolic risk factors associated with abdominal obesity, despite a long-term reduction in body fat.

To study the change in intrapulmonary bacterial growth rate over time during Gram-negative pneumonia, a two-hit model of recurrent bacterial aspiration was developed in mice. A mutant of Klebsiella pneumoniae was isolated that could be distinguished from the wild type when cultured on appropriate media. These strains were intranasally administered, 4 h apart, to mice whose lungs were quantitatively cultured 24 h later. The relative burden of each aspirated inoculum was determined, and, using the administered dose and the number of bacteria from each inoculum present at the end of the experiment, first-order growth constants for each inoculum were calculated. Results indicate that after an initial aspiration of this organism, subsequently aspirated bacteria proliferate more slowly. When two aspirations occurred 4 h apart, the bacteria aspirated first represented 96% of total lung burden at 24 h. The growth constant of the second inoculum was related to the magnitude of the first inoculum in an inverse, nonlinear fashion. When parallel experiments were performed in complement C3-deficient mice, no suppression of the second inoculum was noted, suggesting that early upregulation of antibacterial activity in the lung is a C3-mediated event.