Publications

Curative endoscopic resection is now a viable option for a range of neoplastic lesions of the gastrointestinal tract (GIT) with low invasive potential. Risk of lymph node metastasis is the most important prognostic factor in selecting appropriate lesions for endoscopic therapy, and assessment of invasion depth is vital in this respect. To determine appropriate treatment, detailed endoscopic diagnosis and estimation of depth using magnifying chromoendoscopy is the gold standard in Japan. En bloc resection is the most desirable endoscopic therapy as risk of local recurrence is low and accurate histological diagnosis of invasion depth is possible. Endoscopic mucosal resection is established worldwide for the ablation of early neoplasms, but en bloc removal using this technique is limited to small lesions. Evidence suggests that a piecemeal resection technique has a higher local recurrence risk, therefore necessitating repeated surveillance endoscopy and further therapy. More advanced endoscopic techniques developed in Japan allow effective en bloc removal of early GIT neoplasms, regardless of size. This review discusses assessment of GIT lesions and options for endoscopic therapy with special reference to the introduction of endoscopic submucosal dissection into Western countries.

BACKGROUND & AIMS

Stress signaling, both within and outside the endoplasmic reticulum, has been linked to metabolic dysregulation and hepatic steatosis. Methionine-choline-deficient (MCD) diets cause severe fatty liver disease and have the potential to cause many types of cellular stress. The purpose of this study was to characterize hepatic stress in MCD-fed mice and explore the relationship between MCD-mediated stress and liver injury.

METHODS

Stress signaling was examined in mice fed MCD formulas for 4-21 days. Signaling also was evaluated in mice fed MCD formulas supplemented with clofibrate, which inhibits hepatic triglyceride accumulation. The role of the pro-apoptotic stress protein C/EBP homologous protein (CHOP) in MCD-mediated liver injury was assessed by comparing the responses of wild-type and CHOP-deficient mice to an MCD diet.

RESULTS

MCD feeding caused steatohepatitis coincident with the activation of cJun N-terminal kinase and caspase-12. In contrast, MCD feeding did not activate inositol-requiring protein-1 and actually suppressed the expression of X-box protein-1s. MCD feeding caused weak stimulation of double-stranded RNA-activated protein kinase-like endoplasmic reticulum-resident kinase, but robust activation of general control nonderepressible-2, followed by the phosphorylation of eukaryotic initiating factor-2α and induction of CHOP. Clofibrate eliminated MCD-mediated hepatic steatosis but did not inhibit diet-induced stress. CHOP deficiency did not alleviate, and in fact worsened, MCD-mediated liver disease.

CONCLUSIONS

MCD feeding causes an integrated stress response in the liver rather than a classic unfolded protein response. This stress response does not by itself lead to liver injury. CHOP, despite its identity as a mediator of stress-related cell death, does not play a central role in the pathogenesis of MCD-mediated liver disease.

OBJECTIVES

To examine whether demographic characteristics, health care access, and acute health care utilization differ by age among homeless adults.

METHODS

We interviewed all 2,175 adult attendees of a citywide homeless outreach event.

RESULTS

Older participants were more likely than younger participants to have a regular place for health care (59.8% vs. 44.3%, p<.01), a regular health care provider (53.6% vs. 35.6%, p<.01), and health insurance (45.5% vs. 32.1%, p<.01). Older participants were less likely to be unable to obtain needed health care (15.6% vs. 20.9%, p=.05). In a multivariate analysis, only lack of health insurance predicted inability to obtain needed care (AOR 2.9, CI 1.76-4.8).

CONCLUSIONS

Older and younger homeless adults have similarly high rates of acute health care utilization. The better access to care among older homeless adults speaks to the importance of insurance in determining access to care among homeless adults.

BACKGROUND

Intervention effects estimated from nonrandomized intervention studies are plagued by biases, yet social or structural intervention studies are rarely randomized. There are underutilized statistical methods available to mitigate biases due to self-selection, missing data, and confounding in longitudinal, observational data permitting estimation of causal effects. We demonstrate the use of Inverse Probability Weighting (IPW) to evaluate the effect of participating in a combined clinical and social sexually transmitted infection/human immunodeficiency virus prevention intervention on reduction of incident chlamydia and gonorrhea infections among sex workers in Brazil.

METHODS

We demonstrate the step-by-step use of IPW, including presentation of the theoretical background, data set up, model selection for weighting, application of weights, estimation of effects using varied modeling procedures, and discussion of assumptions for use of IPW.

RESULTS

A total of 420 sex workers contributed 840 data points on incident chlamydia and gonorrhea infection. Participators were compared with nonparticipators following application of inverse probability weights to correct for differences in covariate patterns between exposure groups and between those who remained in the intervention and those who were lost-to-follow-up. Estimators using 4 model selection procedures provided estimates of intervention effect between odds ratio 0.43 (95% CI, 0.22- 0.85) and 0.53 (95% CI, 0.26 -1.1).

CONCLUSIONS

After correcting for selection bias, loss-to-follow-up, and confounding, our analysis suggests a protective effect of participating in the intervention. Evaluations of behavioral, social, and multilevel interventions to prevent sexually transmitted infection can benefit by introduction of weighting methods such as IPW.

In a prospective randomized, controlled trial in Uganda comparing the efficacy of antiretroviral therapy during tuberculosis therapy with the efficacy of tuberculosis therapy alone in HIV-infected patients with tuberculosis who have a CD4(+) cell count >350 cells/microL, it was found that antiretroviral therapy did not accelerate microbiologic, radiographic, or clinical responses to tuberculosis therapy: 18% of participants had sputum smears positive for Mycobacterium tuberculosis after 5 months of tuberculosis therapy, despite having had negative culture results. Trial registration. ClinicalTrials.gov identifier: NCT00078247 .