Fluvastatin reduces oxidative damage in human vascular endothelial cells by upregulating Bcl-2.

BACKGROUND: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been widely used in clinical practise and their efficacy in reducing cardiovascular risk has been well described. OBJECTIVES: To investigate the effect of low doses of fluvastatin (nanomolar) on H(2)O(2)-induced cell damage and the underlying mechanism. METHODS AND RESULTS: Primary cultures of human umbilical vein endothelial cells were used, and the effects of fluvastatin on H(2)O(2)-induced apoptosis, necrosis, and proliferation were observed. H(2)O(2) at a concentration of 100 mum significantly induced apoptotic cell death after 24-h cell culture. Fluvastatin at low concentrations (10-100 nm) prevented H(2)O(2)-induced apoptosis, as determined by a DNA fragmentation assay and by cell counting with trypan blue and Hoechst 33342 nuclei staining. The protective effect of fluvastatin was mediated by the upregulation of Bcl-2 expression as probed by real-time polymerase chain reaction and Western blotting. Using siRNA to knock down the expression of Bcl-2, the protective effect of fluvastatin was abolished. Fluvastatin had no direct effect on the H(2)O(2)-sensitive TRPM2 calcium channel. CONCLUSIONS: These results suggest that fluvastatin has a potent protective effect against H(2)O(2)-induced apoptosis via upregulation of Bcl-2 expression. The findings provide a new insight into the mechanism by which fluvastatin is able to modulate the influence of oxidative stress on vascular endothelial cells.

Nursing home medical directors: ideals and realities.

OBJECTIVE: To evaluate what nursing home medical directors actually do, what they and other nursing home personnel believe would be desirable to do, and what problems and deficiencies are perceived. DESIGN: Mail survey with follow-up telephone interview when necessary. SETTING: Forty-five nursing facilities in upstate New York. PARTICIPANTS: The medical directors, administrators, and directors of nursing of the 45 facilities. MEASUREMENTS: Inventory of what medical directors reported as to their actual activities and time spent, and of what they, the administrators, and the directors of nursing felt should be their responsibilities and activities under ideal circumstances. RESULTS: For part-time medical directors, self-reported time spent on medical directorship activities averaged 12 hours per month; of all directors, 45% spent 8 hours or less per month. Proportion of time spent on various specific activities varied widely. There was general agreement that substantially more time should be spent, in particular, on evaluating and addressing problems of adequacy and quality of care, communicating with attending physicians about problems, and assisting with inservice training programs. CONCLUSIONS: To fill the role adequately, more time should be spent by many part-time medical directors, which will require greater financial commitment by facilities and reimbursement systems. Efforts need to made to better coordinate the expectations of medical directors and facility staff.

Physician response to notification of acute problems in nursing homes.

A frequently cited example of physicians' alleged disinterest in nursing home patients is their failure to respond rapidly or appropriately to telephone calls about acute events or important changes in patient status. This study of 45 SNFs and their 15 attached ICFs evaluated the length of time required to reach physicians by phone about significant clinical changes in patients' conditions and the appropriateness and timeliness of action taken by the physicians once contact was made. Calls on administrative matters, updating of orders, and similar routine calls were excluded. Seven hundred and fifty calls were identified from 24-hour nursing reports; the nature of the problem and the time and details of physicians' responses were recorded from patient charts. Judgment on the quality of physicians' responses was made by consensus of the regional UR committee except in the case of infections where decisions were based on detailed criteria developed in a previous study. The most frequent clinical problems were acute infections (32%), trauma (12%), GI tract disorders (11%), cardiorespiratory problems (10%), neurological disorders (7%), and diabetic control (7%). Results were very encouraging: 96% of physicians' call-backs and actions were judged to be timely, and 87% of physicians' actions taken were judged to be appropriate. However, actions taken were judged inappropriate for certain specific clinical problems, ie, in 22% (54/243) of infections, 24% (4/17) of CVA's, and 12% (6/49) of diabetic control problems. Implications for nursing home care and recommendations for improving the response to acute problems are discussed.

Systemic antibiotic use in nursing homes. A quality assessment.

In this evaluation of the prevalence and quality of systemic antibiotic use in nursing homes, 42 skilled nursing facilities (SNFs) and their 11 attached intermediate care facilities (ICFs) were surveyed. A random sample of 2238 patients (51%) from the total of 4378 beds was selected and of these, 7.7% of the total (8.6% of the SNF and 4.5% of the ICF) patients were on systemic antibiotics on the day of the survey. The most common suspected sites of infection were urinary tract (58.4%), lower respiratory tract (19.1%), and skin or subcutaneous tissue (4.6%). Criteria for appropriateness of initiating systemic antibiotics, for adequacy of initial diagnostic workup, and for appropriate specific antibiotics were developed by the authors, with input from a group of medical directors of nursing homes, based on Centers for Disease Control and Federal Drug Administration guidelines. Evidence to start an antibiotic was judged adequate in 62.4% of cases. Workups were considered inadequate in a high proportion of cases. For example, urinalysis was ordered in only 23.8% and urine culture in 57.4% of suspected urinary tract infections; chest x-ray was ordered in 24.2% and sputum culture in 3.0% of suspected lower respiratory infections. Recommendations are made as to minimum adequate workup for suspected infections and appropriate evidence to justify start of a systemic antibiotic, recognizing the limitations in diagnostic modalities in the nursing home setting and the special problems of their resident populations.