Relationships Between Health Care Disparities and Coverage Policies for Breast,Colon, and Lung Cancer Screening

Disparities in outcomes exist for breast, colon, and lung cancer among diverse populations, particularly racial and ethnic underrepresented minorities (URMs) and individuals from lower socioeconomic status. For example, blacks experience mortality rates up to about 42% higher than whites for these cancers. Furthermore, although overall death rates have been declining, the differential access to screening and care has aggravated disparities. Our purpose is to assess how the coverage policies of CMS and the United States Preventive Services Task Force (USPSTF) influence these disparities. Additionally, barriers are often encountered in accessing screening tests and receiving prompt treatment. To narrow, and potentially eliminate, outcomes disparities, CMS and USPSTF could consider revising their decision-making processes regarding coverage. Some options include (1) extending their evidence base to include observational studies that involve groups at higher risk; (2) lowering the threshold ages for screening to encompass differences in incidence; (3) CMS approving screening CT colonography coverage, which can even increase compliance with other screening tests; (4) clarifying and streamlining guidelines; (5) supporting research on improving access to screening; and (6) encouraging the development of more navigation services for URMs.     

大黄酸鬼臼毒素酯对人骨肉瘤细胞作用机制的研究

目的 研究大黄酸衍生物大黄酸鬼臼毒素酯(RH-01)对人骨肉瘤(HOS)细胞的作用及其机制.方法 体外培养HOS细胞,应用MTT法测定RH-01作用72 h的IC50值,羟基磷灰石吸附实验测定RH-01在体外的骨亲和性,荧光染色观察RH-01对HOS细胞形态的影响,流式细胞仪检测细胞周期分布情况,RT-PCR检测HOS细胞周期蛋白Cyclin D1,CDK4基因表达的变化.结果 RH-01能明显抑制HOS细胞的生长,作用72 h的IC50值为0.18 μmol/L;羟基磷灰石对四环素和RH-01吸附值分别为(8.1±0.15)、(14.8±0.11)μmol/g,RH-01的骨亲和性高于四环素;荧光染色后,可见到经RH-01处理的HOS细胞膜皱褶、卷曲、破裂,核碎裂固缩,聚集成细小的凝聚块;流式细胞仪检测到细胞周期G2 M期阻滞明显;RT-PCR的半定量检测结果 表明Cyclin D1和CDK4 mRNA表达降低.结论 RH-01通过调控细胞周期驱动机制使细胞发生周期阻滞,导致HOS细胞的生长抑制,并且RH-01在体外具有良好的骨亲和性.     

Modulation of tetrodotoxin-resistant sodium channels by dihydropyrazole insecticide RH-3421 in rat dorsal root ganglion neurons

The effects of the dihydropyrazole insecticide RH-3421 on the retrodotoxin-resistant (TTX-R) voltage-gated sodium channels in rat dorsal root ganglion (DRG) neurons were studied using the whole-cell patch clamp technique. RH-3421 at 10 nM to 1 microM completely blocked action potentials. The sodium currents were irreversibly suppressed by 1 microM RH-3421 in a time- and a dose-dependent manner and the IC50 value of RH-3421 was estimated to be 0.7 microM after 10 min of application. RH-3421 blocked the sodium currents to the same extent over the entire range of test potentials. The sodium conductance-voltage curve was not shifted along the voltage axis by 1 microM RH-3421 application In contrast, both fast and slow steady-state sodium channel inactivation curves were shifted in the hyperpolarizing direction in the presence of 1 microM RH-3421. It was concluded that RH-3421 bound to the resting and inactivated sodium channels to cause block with a higher affinity for the latter state.     

Evaluation of student performance in a multi-site clinical clerkship

A method for examining the equivalency of student performance in multi-site clinical clerkships is presented. Six student performance variables within the clerkship are explored: pretest, posttest, oral examination, presentation of a subject review, general clinical performance, and patient write-ups. Student achievement on two external examinations (a University of Washington School of Medicine third-year comprehensive examination and the Part II examination of the National Board of Medical Examiners) is reviewed and compared. This method applied to an obstetrics and gynecology clerkship at the University of Washington reveals no significant differences in student performance among sites on the pretest, oral examination, and both external examinations, but there were differences on four internal measures (posttest, presentations, write-ups, and clinical ratings). The use of this information for clerkship improvement and faculty development is described.     

Pyelonephritis in pregnancy: A prospective randomized trial to prevent recurrent disease evaluating suppressive therapy with nitrofurantoin and close surveillance

It has been advocated that if a patient develops acute pyelonephritis during pregnancy, she should receive suppressive therapy for the remainder of the gestation to prevent a recurrence of the disease. We have prospectively evaluated 200 patients following an acute episode of pyelonephritis during pregnancy. All patients were followed in a special clinic. Half the patients received nitrofurantoin as suppressive therapy. Recurrent pyelonephritis occurred in 7% of the patients receiving suppressive therapy versus 8% of those patients receiving close surveillance in the clinic. The results cast doubt upon the need for suppressive therapy and instead dramatized the beneficial effects of close surveillance with cultures. The data also suggest, at least in a high-risk population, that patients with gram-negative bacilluria of less than 10⁵ colonies/ml may have a substantial risk of developing symptomatic recurrences. Prompt treatment of even low levels of gram-negative bacilluria should be considered in patients at risk for recurrent disease.     

Brain metastases in breast cancer. Epidemiology and natural history. The Institut Curie experience

Breast cancer is the second cause for brain metastases. Their incidence is rising, partly due to the therapeutic improvements which alter the natural history of breast cancer. Predictive factors for brain metastases have been identified: HER2 oncogene overexpression, lack of expression of hormone receptors, young age and triple negative status. Brain metastases prognosis remains poor with a median survival shorter than 1 year, except for solitary lesions treated by surgery or radiosurgery. We have analysed two series of data from Institut Curie (Paris and Saint-Cloud). In women younger than 65 years, with HER2 negative breast carcinoma, median survival was 7.1 months. In women older than 65 years, median survival was 4 months.     

The cardiac sodium channel mRNA is expressed in the developing and adult rat and human brain

Expression of the rat (RH-I/SkM2) and human (hH1/SCN5A) tetrodotoxin-resistant (TTX-R), voltage-sensitive sodium channels is thought to be specific to cardiac tissue. We detected RH-I/SkM2 mRNA in newborn rat brain using both RNase protection assay analysis and in situ hybridization and in adult rat brain using RNase protection assay analysis. This expression was observed primarily in developing limbic structures of the cerebrum and diencephalon, and in the medulla of the brain stem. Using RT-PCR analysis, we detected hH1/SCN5A mRNA in both fetal and adult human brain. Interestingly, mutations in the human cardiac sodium channel are known to lead to cardiac abnormalities, which result in arrhythmias and frequently in sudden cardiac death. If these mutant channels were also expressed in limbic regions of the brain, alterations in channel function could have drastic effects on the brain’s signaling ability, possibly promoting seizure activity.     

Differential sensitivity of rat voltage-sensitive sodium channel isoforms to pyrazoline-type insecticides

Pyrazoline-type insecticides are potent inhibitors of insect and mammalian voltage-sensitive sodium channels. In mammals, there are nine sodium channel alpha subunit isoforms that have unique distributions and pharmacological properties, but no published data exist that compare the relative sensitivity of these different mammalian sodium channel isoforms to inhibition by pyrazoline-type insecticides. This study employed the Xenopus oocyte expression system to examine the relative sensitivity of rat Na(v)1.2a, Na(v)1.4, Na(v)1.5, and Na(v)1.8 sodium channel alpha subunit isoforms to the pyrazoline-type insecticides indoxacarb, DCJW, and RH 3421. Additionally, we assessed the effect of coexpression with the rat beta1 auxiliary subunit on the sensitivity of the Na(v)1.2a and Na(v)1.4 isoforms to these compounds. The relative sensitivity of the four sodium channel alpha subunits differed for each of the three compounds we examined. With DCJW, the order of sensitivity was Na(v)1.4 > Na(v)1.2a > Na(v)1.5 > Na(v)1.8. In contrast, the relative sensitivity of these isoforms to indoxacarb differed from that to DCJW: the Na(v)1.8 isoform was most sensitive, the Na(v)1.4 isoform was completely insensitive, and the sensitivities of the Na(v)1.5 and Na(v)1.2a isoforms were intermediate between these two extremes. Moreover, the pattern of sensitivity to RH 3421 among these four isoforms was different from that for either indoxacarb or DCJW: the Na(v)1.4 isoform was most sensitive to RH 3421, whereas the sensitivities of the remaining three isoforms were substantially less than that of the Na(v)1.4 isoform and were approximately equivalent. The only statistically significant effect of coexpression of either the Na(v)1.2a or Na(v)1.4 isoforms with the beta1 subunit was the modest reduction in the sensitivity of the Na(v)1.2a isoform to RH 3421. These results demonstrate that mammalian sodium channel isoforms differ in their sensitivities to pyrazoline-type insecticides.     

Simultaneous optical mapping of transmembrane potential and intracellular calcium in myocyte cultures

INTRODUCTION: Fast spatially resolved measurements of transmembrane potential (Vm) and intracellular calcium (Ca(i)2+) are important for studying mechanisms of arrhythmias and defibrillation. The goals of this work were (1) to develop an optical technique for simultaneous multisite optical recordings of Vm and Ca(i)2+, and (2) to determine the relationship between Vm and Ca(i)2+ during normal impulse propagation in myocyte cultures. METHODS AND RESULTS: Monolayers of neonatal rat myocytes were stained with fluorescent dye RH-237 (Vm) and Fluo-3AM (Ca(i)2+). Both dyes were excited at the same wavelength range. The emitted fluorescence was optically separated into components corresponding to changes in Vm and Ca(i)2+ and measured using two 16 x 16 photodiode arrays at a spatial resolution of up to 27.5 microm per diode and sampling rate of 2.5 kHz. The optical setup was adjusted so that there was no optical cross-talk between the two types of measurements, which was validated in experiments involving staining with either RH-237 or Fluo-3. The amplitude of Fluo-3 signals rapidly decreased during experiments due to dye leakage. Dye leakage was substantially reduced by application of 1 mM probenecid, a blocker of organic anion transport, which had no effect on action potential duration and only minor effect on conduction velocity. In double-stained preparations, during regular pacing Ca(i)2+ transients had a rise time of 14.2 +/- 2 msec, and they followed Vm upstrokes with a delay of 5.3 +/- 1 msec (n = 9). Durations of Vm and Ca(i)2+ transients determined at 50% level of signal recovery were 54.6 +/- 10 msec and 136 +/- 8 msec, respectively. Application of 2 microM nifedipine reduced the amplitude and duration of Ca(i)2+ transients without significantly affecting conduction velocity. CONCLUSION: The results demonstrate feasibility of simultaneous optical recordings of Vm and Ca(i)2+ transients with high spatial and temporal resolution.