A bayesian strategy for evaluating treatments applicable only to a subset of patients

If we wish to evaluate the efficacy of a proposed treatment applicable only to a subset of the patient population, then a comparison of the results of the proposed treatment with historical experience may be misleading if the applicability of the proposed treatment is itself of prognostic value. We present a Bayesian strategy to estimate the response rate of patients eligible for the proposed treatment but who receive standard therapy; we can compare the results with the experimentally observed response rate of patients who receive the proposed therapy. I extend the approach to apply to time to event data that may be censored, such as time to disease progression. One can use the information obtained in this fashion to evaluate experimental designs for future trials of the proposed treatment.     

Expression and functional analysis of voltage-activated Na+ channels in human prostate cancer cell lines and their contribution to invasion in vitro

Ion channels are important for many cellular functions and disease states including cystic fibrosis and multidrug resistance. Previous work in the Dunning rat model of prostate cancer has suggested a relationship between voltage-activated Na+ channels (VASCs) and the invasive phenotype in vitro. The objectives of this study were to 1) evaluate the expression of VASCs in the LNCaP and PC-3 human prostate cancer cell lines by Western blotting, flow cytometry, and whole-cell patch clamping, 2) determine their role in invasion in vitro using modified Boyden chambers with and without a specific blocker of VASCs (tetrodotoxin). A 260-kd protein representing VASCs was found only in the PC-3 cell line, and these were shown to be membrane expressed on flow cytometry. Patch clamping studies indicated that functional VASCs were present in 10% of PC-3 cells and blocking these by tetrodotoxin (600 nmol/L) reduced their invasiveness by 31% (P = 0.02) without affecting the invasiveness of the LNCaP cells. These results indicate that the reduction of invasion is a direct result of VASC blockade and not a nonspecific action of the drug. This is the first report of VASCs in a human prostatic cell line. VASCs are present in PC-3 but not LNCaP cells as determined by both protein and functional studies. Tetrodotoxin reduced the invasiveness of PC-3 but not LNCaP cells, and these data suggest that ion channels may play an important functional role in tumor invasion.     

Treatment of varicocele for male infertility: a comparative study evaluating currently used approaches

It has been stated that energy adjustment can control for recall bias in case-control studies. Simulation of recall bias and cases and controls in a nutritional survey of German adults was conducted to examine its impact on five dietary effects, (adding a macronutrient, substituting one macronutrient for another, adding a macronutrient while keeping the other energy sources constant, and changing the macronutrient to energy ratio through addition or substitution) using various energy adjustment models. If energy adjustment were an effective means of correcting measurement error, the energy adjusted dietary effects, after a subtraction of energy and fat intake, should equal those in the original data set. Simulation of differential under-reporting of fat and energy intake by cases but not controls showed this to dramatically impact all five considered dietary effects, even after energy adjustment. The influence of the assumed recall bias on the different effects depends on the error type structure, inflating an odds ration of 1.8 to as much as 12.3 or reducing it to 0.45 when 100 kcal of fat was substituted for 100 kcal of other macronutrients. Although energy adjustment may serve many functions, it cannot correct for differential error. Depending upon the nature of the hypothesized effect and the error type, energy adjustment may also distort risk ratios in the presence of non-differential bias. The concern that cases and controls report their energy intakes with different degrees of error remains a critical consideration that must be addressed through improved measurements, and not energy adjustment under any of the currently used models.     

Effects of pulsatile and nonpulsatile coronary perfusion on performance of the canine left ventricle

This study compares the effect of pulsatile (Group C, Fib/P) and nonpulsatile (Group B, Fib/NP) coronary perfusion on myocardial performance during 2 hours of normothermic ventricular fibrillation. Group A (BH/NP), used as a base-line observation, consisted of 2 hours of nonpulsatile coronary perfusion in beating hearts. The assessment of ventricular performance included diastolic ventricular compliance, myocardial oxygen consumption and lactate extraction, regional myocardial blood flow, and histology. After 120 minutes of ventricular fibrillation, Group C showed normal ventricular diastolic compliance as compared to a 50 per cent decrease in Group B (p less than 0.01). Myocardial oxygen consumption was not significantly different from that in Group B. Because of a 70 per cent increase in oxygen extraction above Group B (p less than 0.05), total left ventricular myocardial blood flow was reduced (103 +/- 23 versus 260 +/- 36 ml. per 100 Gm. per minute, p less than 0.05) and had near-constant resistance. Lactate extraction was significantly greater and more stable as compared to Group B (9.28 +/- 1.33 versus 1.8 +/- 1.08, p less than 0.05). Left ventricular endocardial/epicardial flow ratio was greater in Group C (1.21 +/- 0.08 versus 1.06 +/- 0.06, p less than 0.05). Minimal subendocardial histologic changes were present as compared to the marked patchy subendocardial ischemic changes seen in Group B. The results demonstrate that the addition of pulsatile flow to coronary perfusion minimized the deleterious effects of prolonged ventricular fibrillation on myocardial performance.