Publications

BACKGROUND & AIMS

Capsule endoscopy (CE) and double-balloon enteroscopy (DBE) allow complete small-bowel examination but consume additional health care resources. A cost-minimization analysis determined the optimal initial management strategy for obscure occult gastrointestinal bleeding (OGIB).

METHODS

We compared 5 strategies: initial small-bowel follow-through, enteroclysis, push enteroscopy (PE), CE, or DBE. Incorporation of multiple tests was allowed with costs taken from a third-party payer perspective. We modeled medically refractory disease with 2 separate model end points in which treatment or definitive diagnosis was necessary and in which visual diagnosis was sufficient to suspend testing. Sensitivity analyses included variations in parameter estimates, Monte Carlo simulation, and structural variations in the model in which DBE was not available as an initial strategy.

RESULTS

When treatment or definitive diagnosis was necessary, the optimal strategy was initial DBE at a cost of $3824. An initial CE strategy costs an incremental $440. CE was preferred when DBE exceeded $1849 or when the sensitivity of DBE decreased to less than 68%. If DBE was unavailable as an initial test then CE was preferred to PE unless CE exceeded $1190, capsule retention was greater than 3%, or 64% of lesions were within reach of PE. When visual diagnosis was sufficient, initial CE was preferred.

CONCLUSIONS

For OGIB, initial DBE may be the least expensive strategy when treatment or definitive diagnosis is necessary and initial CE may be preferred when visual identification is sufficient. In settings where DBE is not available as an initial test, initial CE may be the preferred strategy.

Under the heading "How tobacco protects you against the flu", the German chemical industry portrays a tobacco grower in an idyllic tobacco plantation. Despite the recent ban of transnational tobacco advertising within the European Union, using tobacco to promote another industry and potential societal health benefits might indirectly promote the social acceptability of tobacco to social leaders. The tobacco control community should thus monitor the use of other industries as a new method to circumvent the tobacco advertising ban and to support the social acceptability of tobacco by associating it with potential health benefits.

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.

Protease inhibitors (PIs) are widely assumed to be associated with a syndrome of insulin resistance accompanied by hyperlipidemia and fat redistribution. Insulin resistance in HIV infection has numerous other causes, however, which include not only the direct effects of antiretroviral drugs but also factors such as aging and restoration to health accompanied by fat accumulation. Studies of PIs in HIV-infected and noninfected patients indicate that some of these drugs are associated with reduced insulin sensitivity (greater acute versus chronic effects) that may be due to direct blockade of the insulin-sensitive glucose transporter in muscle and fat cells. Other studies have shown that insulin levels increase over time with antiretroviral therapy, likely the result of improved health, fat accumulation, and aging, and that increases in visceral fat and upper trunk fat are associated with a higher risk of insulin resistance in HIV-infected and -uninfected individuals alike. This article summarizes a presentation on insulin resistance in HIV infection made by Carl Grunfeld, MD, PhD, at the 10th Annual Ryan White HIV/AIDS Program Clinical Update in Phoenix in June 2007.

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.

Described as the body's largest organ, the skin is strategically located at the interface with the external environment where it has evolved to detect, integrate and respond to a diverse range of stressors. A flurry of recent findings has established the skin as an important peripheral (neuro)endocrine organ that is tightly networked to central stress axes. This capability is contributing to the maintenance of body homeostasis, and in this way could be harnessed for therapeutic strategies.

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.