Expression of Q227L-galphas in MCF-7 human breast cancer cells inhibits tumorigenesis.

The effects of expression of mutant (Q227L)-activated Galphas and elevation of cAMP on mitogen-activating protein kinase (MAPK) activity and the transformed phenotype were studied in the MCF-7 human mammary epithelial cell line. Elevation of cAMP partially inhibited the epidermal growth factor-stimulated DNA synthesis and the intrinsic MAPK (ERK-1 and ERK-2) of serum-starved MCF-7 cells. Addition of 8Br-cAMP or expression of mutant (Q227L)-activated Galphas in MCF-7 cells blocked the ability of these cells to grow in an anchorage-independent manner, as assessed by colony formation in soft agar. 8Br-cAMP in the culture medium also blocked estrogen stimulation of MCF-7 cell proliferation in vitro. MCF-7 cells expressing Q227L-Galphas grew very slowly in vitro, and when these cells were injected s.c. into athymic mice implanted with estrogen pellets, the frequency of tumor formation was reduced greatly and the sizes of the tumors formed were much smaller than those in mice injected with MCF-7 cells that had been transfected with the empty vector. These results indicate that the intracellular levels of cAMP in transformed mammary epithelial cells can be a crucial factor in determining the expression of the transformed phenotype. Interactions between the Gs/adenylyl cyclase and MAPK-1,2 signaling pathways could be one mechanism by which expression of the transformed phenotype in mammary epithelial cells are regulated.

A study of proactive ethics consultation for critically and terminally ill patients with extended lengths of stay.

OBJECTIVE: To assess the effect of proactive ethics consultation on documented patient care communications and on decisions regarding high-risk intensive care unit (ICU) patients. DESIGN: Prospective, controlled study. PATIENTS: Ninety-nine ICU patients treated with >96 hrs of continuous mechanical ventilation. INTERVENTIONS: Three groups were compared: a) a baseline group enrolled in the study prior to the establishment of the hospital's ethics consultation service; b) a control group where ethics consultation was at the option of the care team; and c) a treatment group where the ethics service intervened proactively after patients received >96 hrs of continuous mechanical ventilation. Patient care planning, for subjects in the proactive group, was reviewed with physicians and with the care team using a standardized set of prompting questions designed to focus discussion of key decision-making and communication issues for critically and terminally ill patients. Issues and concerns were identified and action strategies were suggested to those in charge of the patient's care. Formal ethics consultation, using a patient care conference model, was made available upon request. MEASUREMENTS AND MAIN RESULTS: Post discharge chart reviews of the three groups indicated no statistically significant differences on important demographic variables including age, gender, and acuity. Comparisons of survivors and nonsurvivors for the three groups indicated, at statistically significant levels, more frequent and documented communications, more frequent decisions to forego life-sustaining treatment, and reduced length of stay in the ICU for the proactive consultation group. CONCLUSION: Proactive ethics consultation for high-risk patient populations offers a promising approach to improving decision-making and communication and reducing length of ICU stay for dying patients.

The evolution of functional endoscopic sinus surgery in the Commonwealth of Virginia.

This is the largest retrospective analysis of sinus surgery ever reported involving 5,860 surgical as well as 6,769 diagnostic sinus procedures during a six year period, 1988-1993. During this time interval, the frequency of endoscopic procedures has increased dramatically. Because of the increased frequency of this procedure, we see the need for strict definition of the clinical indications for surgery for patients with chronic or acute sinusitis. In addition, the number of open procedures, namely the Caldwell-Luc procedure, as a treatment for sinusitis remained relatively constant despite the frequent use of endoscopic technique. Because of the endoscopic surgery's increased acceptance and advantages over the open surgical technique, we emphasize the need for continuing educational programs to train surgeons to perform the endoscopic procedure or referral of the patient to an otolaryngologist experienced in this technique.