Evaluation of decision rules for identifying low bone density in postmenopausal African-American women

OBJECTIVE: While African-American women tend to have greater bone mineral density (BMD) than caucasian women, they are still at risk of developing osteoporosis later in life. Clinical decision rules (i.e., algorithms) have been developed to assist clinicians identify women at greatest risk of low BMD. However, such tools have only been validated in caucasian and Asian populations. Accordingly, the objective of this study was to compare the performance of five clinical decision rules in identifying postmenopausal African-American women at greatest risk for low femoral BMD. METHODOLOGY: One hundred-seventy-four (n=174) postmenopausal African-American women completed a valid and reliable oral questionnaire to assess lifestyle characteristics, and completed height and weight measures. BMD at the femoral neck was measured via dual energy x-ray absorptiometry (DXA). We calculated sensitivity, specificity, positive predictive value, and negative predictive value for identifying African-American women with low BMD (T-Score < or = -2.0 SD) using five clinical decision rules: Age, Body Size, No Estrogen (ABONE), Osteoporosis Risk Assessment Instrument (ORAI), Osteoporosis Self-Assessment Tool (OST), Simple Calculated Osteoporosis Risk Estimation (SCORE), and body weight less than 70 kg. RESULTS: Approximately 30% of African-American women had low BMD, half of whom had osteoporosis (BMD T-Score < or = -2.5 SD). Sensitivity for identifying women with a low BMD (T-Score < or = -2.0 SD) ranged from 65.57-83.61%, while specificity ranged from 53.85-78.85%. Positive predictive values ranged from 80.95-87.91%, while negative predictive values ranged from 48.44-58.33%. CONCLUSION: Our data suggest that the clinical decision rules analyzed in this study have some usefulness for identifying postmenopausal African-American women with low BMD. However, there is a need to establish cut-points for these clinical decision rules in a larger, more diverse sample of African-American women.     

Taxol-induced cell cycle arrest and apoptosis: dose-response relationship in lung cancer cells of different wild-type p53 status and under isogenic condition

The effective dose, schedule, molecular basis of the cytotoxicity of taxol and their dependence on the genetic background in tumor cells are still not well understood. Here, we examined how the dose-response relationship for taxol varies in lung cancer cells with different p53 status and under isogenic conditions. DNA content analyses in A 549 (p53, +/+) and H 1299 (p53, -/-) cells, showed that taxol progressively induced G2/M arrest in both cell lines in a concentration-dependent manner, which was accompanied by a parallel decrease in the G1 population. G2/M arrest, however, occurred at a lower concentration in A 549 cell lines than in H 1299 cells. The S-phase population in A 549 cells was not significantly changed up to 0.025 microM, but dropped by six-fold at 1.0 microM taxol, in contrast to that in H 1299 cells. A sub-G1 apoptotic population was present at 24 h, even at 0.002 microM taxol, when G2/M arrest was not appreciably detected. In both cell lines, the maximum apoptosis of about 28% was achieved at 0.025 microM taxol, implicating that wild-type p53 does not modulate the level of taxol-induced apoptosis. When we examined the role of the wild-type p53 in isogenic cell lines developed in a H 1299 background, the maximum level of apoptosis was in the range of 28-34% at a drug concentration around 0.03 microM, not significantly different from that observed in parental H 1299 cells. We conclude that taxol is effective in inducing apoptosis at very low doses (0.020-0.035 microM), and that the presence or absence of the wild-type p53 does not make a statistically significant difference in the level of apoptotic cell death in these lung cancer cell lines, but the maximum is attained at a lower drug concentration in the presence of p53.     

6-minute walk work for assessment of functional capacity in patients with COPD

The 6-min walk (6MW) test is commonly used to assess exercise capacity in patients with COPD and to track functional change resulting from disease progression or therapeutic intervention. Not surprisingly, distance covered has been the preferred outcome for this test. However, distance walked does not account for differences in body weight that are known to influence exercise capacity. OBJECTIVE: The aim of this study was to evaluate the 6-min distance x body weight product (6MWORK) as an improved outcome measure with a solid physiologic foundation. PATIENTS AND METHODS: One hundred twenty-four men and women with moderate-to-severe COPD volunteered and completed the testing sequence, which included pulmonary function, a peak effort ramp cardiopulmonary exercise study with gas exchange, and the 6MW. Means and SD were generated for the variables of interest. Differences were analyzed using analysis of variance techniques. Correlation coefficients and receiver operating characteristic (ROC) curves were calculated for the 6-min walk distance (6MWD) and 6MWORK with indexes of pulmonary function, work performance, and Borg scores for dyspnea and effort. RESULTS: Men and women presented with a significant smoking history that also differed by gender (48 vs 66 pack-years, respectively; p < 0.01). The mean (+/- SD) FEV(1) values were 45 +/- 12.6% and 48 +/- 12.1%, respectively (not significant), while the diffusing capacity of the lung for carbon monoxide (DLCO) was 14.7 +/- 6.1 vs 10.3 +/- 3.9 mL/min/mm Hg, respectively (p < 0.001), for men and women. The 6MWD averaged 416.8 +/- 79.0 m for men and 367.8 +/- 78.6 m for women, and these differences were significant (p < 0.002). When 6MWD was compared as the percent predicted of normal values, each gender presented with a similar reduction of 78.6 +/- 14.5% vs 79.9 +/- 17.5% (p > 0.05), respectively. 6MWORK averaged 35,370 +/- 9,482 kg/m and 25,643 +/- 9,080 kg/m (p < 0.0001) for men and women, respectively. 6MWORK yielded higher correlation coefficients than did 6MWD when correlated with DLCO, lung diffusion for alveolar ventilation, FEV(1), FEV(1)/FVC ratio, watts, peak oxygen uptake, peak minute ventilation, and peak tidal volume. The ROC curve demonstrated that 6MWORK had a significantly larger calculated area under the curve (p < 0.05) [plot of 100-sensitivity to specificity for each variable of interest for all subjects] than 6MWD when differentiating an objectively selected definition of low work capacity vs high work capacity (bike ergometry work, < 55 vs > 55 W, respectively). CONCLUSIONS: We conclude that work calculated as the product of distance x body weight is an improved outcome measure for the 6MW. 6MWORK can be used whenever the 6MW is required to estimate a patient's functional capacity. This measure is also a common measure, which can be converted to indexes of caloric expenditure for direct cross-modality comparisons.