Faculty Bibliography

Metastatic breast cancer may emerge from latent tumor cells that remain dormant at disseminated sites for many years. Identifying mechanisms regulating the switch from dormancy to proliferative metastatic growth has been elusive due to the lack of experimental models of tumor cell dormancy. We characterized the in vitro growth characteristics of cells that exhibit either dormant (D2.0R, MCF-7, and K7M2AS1.46) or proliferative (D2A1, MDA-MB-231, and K7M2) metastatic behavior in vivo. Although these cells proliferate readily in two-dimensional culture, we show that when grown in three-dimensional matrix, distinct growth properties of the cells were revealed that correlate to their dormant or proliferative behavior at metastatic sites in vivo. In three-dimensional culture, cells with dormant behavior in vivo remained cell cycle arrested with elevated nuclear expression of p16 and p27. The transition from quiescence to proliferation of D2A1 cells was dependent on fibronectin production and signaling through integrin beta1, leading to cytoskeletal reorganization with filamentous actin (F-actin) stress fiber formation. We show that phosphorylation of myosin light chain (MLC) by MLC kinase (MLCK) through integrin beta1 is required for actin stress fiber formation and proliferative growth. Inhibition of integrin beta1 or MLCK prevents transition from a quiescent to proliferative state in vitro. Inhibition of MLCK significantly reduces metastatic outgrowth in vivo. These studies show that the switch from dormancy to metastatic growth may be regulated, in part, through epigenetic signaling from the microenvironment, leading to changes in the cytoskeletal architecture of dormant cells. Targeting this process may provide therapeutic strategies for inhibition of the dormant-to-proliferative metastatic switch.

Amidst recent policy discussions about the health care safety net there has been relatively little information about whether the actual site of care affects care quality. We therefore used National Health Interview Survey data to describe low-income adults seeking primary care at different types of sites and the quality of access and preventive care at these sites. After adjusting for sociodemographic characteristics and illness burden, hospital-outpatient- department patients were more likely to receive vaccinations for influenza (adjusted odds ratio [AOR] 1.3, 95% confidence interval [CI] 1.0-1.6) and pneumococcus (AOR 1.4, 95% CI 1.1-1.8) than were those at clinics or health centers. Hospital-clinic patients were more likely to report delays in care due to office administrative difficulties (AOR 1.3, 95% CI 1.1-1.7) and more likely to have more than one emergency room visit (AOR 1.9, 95% CI 1.5-2.3). Physicians' office or HMO patients were less likely to report administrative delays in care than those at clinics or health centers, but there were no other differences in quality between these two site types. Policymakers and health care services analysts and providers must monitor quality as they decide how best to deliver care to vulnerable populations

BACKGROUND:Clinical prediction rules (CPR) are tools that clinicians can use to predict the most likely diagnosis, prognosis, or response to treatment in a patient based on individual characteristics. CPRs attempt to standardize, simplify, and increase the accuracy of clinicians' diagnostic and prognostic assessments. The teaching tips series is designed to give teachers advice and materials they can use to attain specific educational objectives. EDUCATIONAL OBJECTIVES/OBJECTIVE:In this article, we present 3 teaching tips aimed at helping clinical learners use clinical prediction rules and to more accurately assess pretest probability in every day practice. The first tip is designed to demonstrate variability in physician estimation of pretest probability. The second tip demonstrates how the estimate of pretest probability influences the interpretation of diagnostic tests and patient management. The third tip exposes learners to various examples and different types of Clinical Prediction Rules (CPR) and how to apply them in practice. PILOT TESTING: We field tested all 3 tips with 16 learners, a mix of interns and senior residents. Teacher preparatory time was approximately 2 hours. The field test utilized a board and a data projector; 3 handouts were prepared. The tips were felt to be clear and the educational objectives reached. Potential teaching pitfalls were identified. CONCLUSION/CONCLUSIONS:Teaching with these tips will help physicians appreciate the importance of applying evidence to their every day decisions. In 2 or 3 short teaching sessions, clinicians can also become familiar with the use of CPRs in applying evidence consistently in everyday practice.

PURPOSE: To examine the effects of bias and distortion from general health status on Rasch model-based measurements of visual function, and establish measurement equivalence across different health status groups in low vision patients. METHODS: Self-reported data were obtained from 1746 low vision patients who completed the Activity Inventory (AI) and an intake health-related questionnaire prior to their first visit to the low vision rehabilitation service. Differential Item Functioning (DIF) analysis by health status and separate Rasch analyses adjusted by health status were performed on the responses to both a DIF-free scale and the full scale of the AI. RESULTS: Of 48 Goal-level items, only 15 items showed significant DIF (P < 0.001). Comparing the vision-related estimates from the original full set of items with those from the DIF free scale; we found that only 25% of the person measure estimates differed by 0.5 logits or more and there was a strong intraclass correlation between the two scales in measuring the patients' vision-related functional ability (IC = 0.75). Patients' health status influenced the Rasch model based estimation of visual function by the AI (ANOVA, p = 0.005), but this effect was within accepted range of MISFIT statistics. CONCLUSION: Taken together, our results indicate that despite confounding effects of general health status on vision-related ability, we can still regard visual ability to be a single theoretically constructed variable for the low vision population. It appears that self-perceived comorbidities add to vision-related disability, but do not distort its measurement.

The consumer group Public Citizen asked the FDA in 2006 to put a black-box warning on Cipro and other fluoroquinolones. According to the FDA, fluoroquinolones can increase the risk of tendon inflammation and rupture from 1 in 100,000 patients to 3 or 4 in 100,000 patients. But this increased risk is miniscule when you consider the number of lives Levaquin or Cipro save in patients with pneumonia, infectious colitis or serious urinary tract infections. Medications should be prescribed on a case-by-case basis and should be based on reason rather than emotion

If black America were a country, it would rank 16th in the world in the number of people living with the AIDS virus, the Black AIDS Institute, an advocacy group, reported Tuesday. Dr. Helene Gayle, president of CARE and a former director of H.I.V. prevention efforts at the disease control centers, told reporters on Tuesday that the United States needed to devote more resources to care for people with sexually transmitted diseases

Dr. Helene Gayle, president of CARE and a former director of HIV prevention efforts at the disease control centers, told reporters on Tuesday that the United States needed to devote more resources to care for people with sexually transmitted diseases.

If black America were a country, it would rank 16th in the world in the number of people living with the AIDS virus, the Black AIDS Institute, an advocacy group, reported on Tuesday.