Publications

Until recently, most clinical guidelines in the United States were in general agreement about the tests available for colorectal cancer screening, recommending fecal occult blood tests every year, flexible sigmoidoscopy every 5 years, both these tests together, double contrast barium enema every 5 years, or colonoscopy every 10 years. However, the release of two new sets of guidelines in 2008 has made it necessary for primary care physicians to update their knowledge of the recommended screening options. The most influential factor in determining whether a patient is screened is recommendation from a physician. The primary goal of this article is to review and critique the new guidelines for average-risk screening in adults older than 50 years. Armed with this information, primary care physicians will be better educated as to the importance of offering screening to their patients, as well as the strength and weaknesses of each recommended test.

The majority of percutaneous coronary interventions (PCIs) are carried out in nonurgent situations, primarily in patients with stable coronary artery disease. Recent trials have concluded that for patients with stable coronary artery disease, treatment with optimal medical therapy versus optimal medical therapy plus PCI yields equivalent outcomes in terms of morbidity and future risk of myocardial infarction. Since PCI is a procedure with risk, it is important to identify patients for whom the benefit of the procedure outweighs the harms. PCI may be beneficial in certain subgroups, such as patients with moderate-to-severe ischemia on noninvasive testing. Although current guidelines require documentation of ischemia prior to elective PCI and this strategy is cost effective, pre-PCI stress testing appears to be underutilized, potentially leading to PCI being performed in patients who may not derive benefit from the procedure.

BACKGROUND

Transplantation of stem cells from various sources into infarcted hearts has the potential to promote myocardial regeneration. However, the regenerative capacity is limited partly as a result of the low survival rate of the transplanted cells in the ischemic myocardium. In the present study, we tested the hypothesis that combining cell and angiogenic gene therapies would provide additive therapeutic effects via co-injection of bone marrow-derived mesenchymal stem cells (MSCs) with an adeno-associated viral vector (AAV), MLCVEGF, which expresses vascular endothelial growth factor (VEGF) in a cardiac-specific and hypoxia-inducible manner.

METHODS

MSCs isolated from transgenic mice expressing green fluorescent protein and MLCVEGF packaged in AAV serotype 1 capsid were injected into mouse hearts at the border of ischemic area, immediately after occlusion of the left anterior descending coronary, individually or together. Engrafted cells were detected and quantified by real-time polymerase chain reaction and immunostaining. Angiogenesis and infarct size were analyzed on histological and immunohistochemical stained sections. Cardiac function was analyzed by echocardiography.

RESULTS

We found that co-injection of AAV1-MLCVEGF with MSCs reduced cell loss. Although injection of MSCs and AAV1-MLCVEGF individually improved cardiac function and reduced infarct size, co-injection of MSC and AAV1-MLCVEGF resulted in the best improvement in cardiac function as well as the smallest infarct among all groups. Moreover, injection of AAV1-MLCVEGF induced neovasculatures. Nonetheless, injection of MSCs attracted endogenous stem cell homing and increased scar thickness.

CONCLUSIONS

Co-injection of MLCVEGF and MSCs in ischemic hearts can result in better cardiac function and MSC survival, compared to their individual injections, as a result of the additive effects of each therapy.

BACKGROUND

Mutations in the human filaggrin gene (FLG) are associated with atopic dermatitis (AD) and are presumed to provoke a barrier abnormality. Yet additional acquired stressors might be necessary because the same mutations can result in a noninflammatory disorder, ichthyosis vulgaris.

OBJECTIVE

We examined here whether FLG deficiency alone suffices to produce a barrier abnormality, the basis for the putative abnormality, and its proinflammatory consequences.

METHODS

By using the flaky-tail mouse, which lacks processed murine filaggrin because of a frameshift mutation in the gene encoding profilaggrin that mimics some mutations in human AD, we assessed whether FLG deficiency provokes a barrier abnormality, further localized the defect, identified its subcellular basis, and assessed thresholds to irritant- and hapten-induced dermatitis.

RESULTS

Flaky-tail mice exhibit low-grade inflammation with increased bidirectional, paracellular permeability of water-soluble xenobiotes caused by impaired lamellar body secretion and altered stratum corneum extracellular membranes. This barrier abnormality correlates with reduced inflammatory thresholds to both topical irritants and haptens. Moreover, when exposed repeatedly to topical haptens at doses that produce no inflammation in wild-type mice, flaky-tail mice experience a severe AD-like dermatosis with a further deterioration in barrier function and features of a T(H)2 immunophenotype (increased CRTH levels plus inflammation, increased serum IgE levels, and reduced antimicrobial peptide [mBD3] expression).

CONCLUSIONS

FLG deficiency alone provokes a paracellular barrier abnormality in mice that reduces inflammatory thresholds to topical irritants/haptens, likely accounting for enhanced antigen penetration in FLG-associated AD.

BACKGROUND

Noninfectious nonallergic rhinitis (NINAR) is characterized by self-reported hyperreactivity to nonspecific physical or chemical stimuli. The relationship between these two classes of triggers is not well established, however. We compared NINAR subjects with predominantly physical or chemical triggers versus normal controls with respect to subjective (symptomatic) and objective (obstructive) responses to cold, dry air challenge.

METHODS

We studied 14 NINAR subjects and 10 normal controls. Exposures consisted of 15 minutes of cold dry air (0 degrees C/5% RH) or warm moist air (25 degrees C/50% RH) on two separate days a week apart. Subjects rated symptoms using visual analog scales and had their nasal airway resistance measured at baseline, immediately after, and at 15-minute intervals for 1 hour postexposure.

RESULTS

The majority of NINAR subjects reported physical triggers as more troublesome than chemical. Immediately postprovocation, the mean net proportional change in nasal airway resistance from baseline was +0.18 in NINAR (physical), +0.05 in NINAR (chemical), and -0.01 in control subjects (NS). However, a pooled linear regression by number of physical triggers (0-5) revealed a 7.5% increase in cold air-induced nasal airway resistance per trigger reported (p<0.05). Similarly, raising the criterion number of physical triggers from >or=1 to >or=2 also distinguished NINAR subjects from controls in a bivariate analysis.

CONCLUSION

Either considering self-reported physical triggers as a continuous scale (0-5) or requiring more physical triggers (>or=2 rather than >or=1) to define NINAR successfully predicts objective nasal reactivity to cold air provocation.

In the post-Human Genome Project era, the debate on the concept of race/ethnicity and its implications for biomedical research are dependent on two critical issues: whether and how to classify individuals and whether biological factors play a role in health disparities. The advent of reliable estimates of genetic (or biogeographic) ancestry has provided this debate with a quantitative and more objective tool. The estimation of genetic ancestry allows investigators to control for population stratification in association studies and helps to detect biological causation behind population-specific differences in disease and drug response. New techniques such as admixture mapping can specifically detect population-specific risk alleles for a disease in admixed populations. However, researchers have to be mindful of the correlation between genetic ancestry and socioeconomic and environmental factors that could underlie these differences. More importantly, researchers must avoid the stigmatization of individuals based on perceived or real genetic risks. The latter point will become increasingly sensitive as several 'for profit companies' are offering ancestry and genetic testing directly to consumers and the consequences of the spread of the services of these companies are still unforeseeable.

OBJECTIVE

This project analyzed the psychometric properties of the Agency for Healthcare Research and Quality Hospital Survey on Patient Safety Culture (HSOPSC) including factor structure, interitem reliability and intraclass correlations, usefulness for assessment, predictive validity, and sensitivity.

METHODS

The survey was administered to 454 health care staff in 3 hospitals before and after a series of multidisciplinary interventions designed to improve safety culture. Respondents (before, 434; after, 368) included nurses, physicians, pharmacists, and other hospital staff members.

RESULTS

Factor analysis partially confirmed the validity of the HSOPSC subscales. Interitem consistency reliability was above 0.7 for 5 subscales; the staffing subscale had the lowest reliability coefficients. The intraclass correlation coefficients, agreement among the members of each unit, were within recommended ranges. The pattern of high and low scores across the subscales of the HSOPSC in the study hospitals were similar to the sample of Pacific region hospitals reported by the Agency for Healthcare Research and Quality and corresponded to the proportion of items in each subscale that are worded negatively (reverse scored). Most of the unit and hospital dimensions were correlated with the Safety Grade outcome measure in the tool.

CONCLUSION

Overall, the tool was shown to have moderate-to-strong validity and reliability, with the exception of the staffing subscale. The usefulness in assessing areas of strength and weakness for hospitals or units among the culture subscales is questionable. The culture subscales were shown to correlate with the perceived outcomes, but further study is needed to determine true predictive validity.