Publications

OBJECTIVE

Hepatic ischemia-reperfusion can be associated with acute lung injury. Alveolar epithelial type II cells (ATII) play an important role in maintaining lung homeostasis in acute lung injury.

DESIGN

To study potentially new mechanisms of hepatic ischemia-reperfusion-induced lung injury, we examined how liver ischemia-reperfusion altered the proteome of ATII.

SETTING

Laboratory investigation.

SUBJECTS

Spontaneously breathing male Zucker rats.

INTERVENTIONS

Rats were anesthetized with isoflurane. The vascular supply to the left and medial lobe of the liver was clamped for 75 mins and then reperfused. Sham-operated rats were used as controls. After 8 hrs, rats were killed.

MEASUREMENTS AND MAIN RESULTS

Bronchoalveolar lavage and differential cell counts were performed, and tumor necrosis factor-alpha and cytokine-induced neutrophil chemotactic factor-1 in plasma were determined by enzyme-linked immunosorbent assay. ATII were isolated, lysed, tryptically digested, and labeled using isobaric tags (iTRAQ). The samples were fractionated by cation exchange chromatography, separated by high-performance liquid-chromatography, and identified using electrospray tandem mass spectrometry. Spectra were interrogated and quantified using ProteinProspector. Quantitative proteomics provided quantitative data for 94 and 97 proteins in the two groups. Significant changes in ATII protein content included 30% to 40% increases in adenosine triphosphate synthases, adenosine triphosphate/adenosine diphosphate translocase, and catalase (all p < .001). Following liver ischemia-reperfusion, there was also a significant increase in the percentage of neutrophils in bronchoalveolar lavage (48% +/- 26%) compared with sham-operated controls (5% +/- 3%) (p < .01), and plasma tumor necrosis factor-alpha levels were also significantly increased.

CONCLUSIONS

The proteins identified by quantitative proteomics indicated significant changes in moderators of cell metabolism and host defense in ATII. These findings provide new insights into possible mechanisms responsible for hepatic ischemia-reperfusion-related acute lung injury and suggest that ATII cells in the lung sense and respond to hepatic injury.

BACKGROUND

Studies in persons without HIV infection have compared percentage body fat (%BF) and waist circumference as markers of risk for the complications of excess adiposity, but only limited study has been conducted in HIV-infected subjects.

OBJECTIVE

We compared anthropometric and magnetic resonance imaging (MRI)-based adiposity measures as correlates of metabolic complications of adiposity in HIV-infected and control subjects.

DESIGN

The study was a cross-sectional analysis of 666 HIV-positive and 242 control subjects in the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) study assessing body mass index (BMI), waist (WC) and hip (HC) circumferences, waist-to-hip ratio (WHR), %BF, and MRI-measured regional adipose tissue. Study outcomes were 3 metabolic risk variables [homeostatic model assessment (HOMA), triglycerides, and HDL cholesterol]. Analyses were stratified by sex and HIV status and adjusted for demographic, lifestyle, and HIV-related factors.

RESULTS

In HIV-infected and control subjects, univariate associations with HOMA, triglycerides, and HDL were strongest for WC, MRI-measured visceral adipose tissue, and WHR; in all cases, differences in correlation between the strongest measures for each outcome were small (r

CONCLUSION

Relations of simple anthropometric measures with HOMA, triglycerides, and HDL cholesterol are approximately as strong as MRI-measured whole-body adipose tissue depots in both HIV-infected and control subjects.

OBJECTIVE

Inflammation is a potential mechanism to explain the accelerated atherosclerosis observed in HIV- and hepatitis C virus (HCV)-infected persons. We evaluated C-reactive protein (CRP) in HIV-infected and HIV/HCV-coinfected individuals in the era of effective antiretroviral (ARV) therapy.

DESIGN

Cross-sectional study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM) cohort and controls from the Coronary Artery Risk Development in Young Adults (CARDIA) study.

METHODS

CRP levels were measured in 1135 HIV-infected participants from the FRAM cohort and 281 controls from the CARDIA study. The associations of HIV and HIV/HCV infection with CRP levels were estimated by multivariable linear regression.

RESULTS

Compared with controls, HIV monoinfection was associated with an 88% higher CRP level in men (P < 0.0001) but with no difference in women (5%; P = 0.80) in multivariate analysis. CRP levels were not associated with ARV therapy, HIV RNA level, or CD4 cell count. Compared with controls, HIV/HCV coinfection was associated with a 41% lower CRP level in women (P = 0.012) but with no difference in men (+4%; P = 0.90). Among HIV-infected participants, HCV coinfection was associated with 50% lower CRP levels after multivariable analysis (P < 0.0001) in men and women. Greater visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were strongly associated with CRP levels. Among HIV-infected participants, CRP levels were 17% (P < 0.001) and 21% (P = 0.002) higher per doubling of VAT and SAT; among controls, CRP levels were 34% (P < 0.001) and 61% (P = 0.009) higher, respectively.

CONCLUSIONS

In the absence of HCV coinfection, HIV infection is associated with higher CRP levels in men. HCV coinfection is associated with lower CRP levels in men and women.

BACKGROUND

Veterans Affairs medical centers (VAMCs) provide better preventive and chronic disease care when compared with other health care organizations, although recent health care quality improvement initiatives outside the VAMC sector may have narrowed quality differences.

METHODS

Using the nationally representative 2000 and 2004 surveys of the Behavior Risk Factor Surveillance System, which included 152,310 community-dwelling insured adults in 2000 and 251,570 in 2004, we compared self-reported use of 17 recommended ambulatory care services for cancer prevention, cardiovascular risk reduction, diabetes mellitus management, and infectious disease prevention among insured adults receiving and not receiving care at VAMCs.

RESULTS

A total of 2852 insured adults (1.9%) received care at VAMCs in 2000 and 7155 (2.4%) received care at VAMCs in 2004. Use of 9 of the 17 services was greater in 2004 when compared with 2000 (P < or = .05). In 2000, receiving VAMC care was associated with greater use of 6 of the 17 services; in 2004, receiving VAMC care was associated with greater use of 12 of the 17 services (P < or = .05). In 2004, greater use among these 12 services ranged from 10% greater use of cholesterol screening to 40% greater use of colorectal cancer screening. For 13 of the 17 services, the likelihood of service use among adults receiving VAMC care when compared with adults not receiving VAMC care was not significantly different in 2004 than in 2000. However, this likelihood was significantly greater (for VAMC vs non-VAMC use) in 2004 than in 2000 for breast cancer screening (relative risk [RR], 1.21 [95% confidence interval {CI}, 1.15-1.25] vs 0.80 [95% CI, 0.58-0.98]; P < .001), dilated eye examination among adults with diabetes (RR, 1.12 [95% CI, 1.07-1.15] vs 1.01 [95% CI, 0.88-1.09]; P = .04), and influenza (RR, 1.30 [95% CI, 1.24-1.36] vs 1.06 [95% CI, 0.89-1.21]; P = .006) and pneumococcal (RR, 1.27 [95% CI, 1.23-1.31] vs 1.04 [95% CI, 0.86-1.21]; P = .005) vaccinations.

CONCLUSION

Despite increasing emphasis on quality of care and improved performance throughout the US health care system, adults receiving VAMC care remain more likely to receive recommended ambulatory care.

The ideal treatment strategy for Crohn's disease (CD) remains uncertain, as does the optimal endpoint of therapy. Top-down versus step-up describes two different approaches: early use of immunomodulators and biological agents in the former versus initial treatment with steroids in the latter, with escalation to immunomodulators or biological drugs in patients proven to be steroid refractory or steroid dependent. Top-down therapy has been associated with higher rates of mucosal healing. If mucosal healing proves to be associated with better long-term outcomes, such as a decreased need for hospitalization and surgery, top-down therapy may be the better approach for many patients. The main concern with the top-down approach is the toxicity of the immunomodulators and biological agents, which have been linked with infectious complications as well as an increased risk of lymphoma. It is unlikely that one strategy will be best for all patients given the underlying heterogeneity of CD presentation and severity. Ultimately, we must weigh the safety and efficacy of the therapies with the risks of the disease itself. Unfortunately our ability to risk stratify patients at diagnosis remains rudimentary. The purpose of this paper is to review the data that supports or refutes the differing treatment paradigms in CD, and to provide a rationale for an approach, termed the "accelerated step-up" approach, which attempts to balance the risks and benefits of our currently available therapies with the risk of disease related complications as we understand them in 2008.