Search

A growing body of evidence from clinical trials and epidemiological studies has identified elevated resting heart rate as a predictor of clinical events. Proof of direct cause and effect is limited, because current drugs that lower heart rate (eg, beta-blockers) have multiple mechanisms of action. A new class of drug, selective If inhibitors, is under investigation as a ‘pure’ heart rate-reducing medication and will help confirm if there is a causal link between elevated heart rate and cardiovascular outcomes. The present paper reviews the evidence for elevated heart rate as a cardiovascular risk factor and some of the current clinical trials testing this hypothesis.

The current study documented the implementation of three‐dimensional conformal radiotherapy and assessed the tumor control and toxicity of such treatment in a large, multisite community practice.The authors retrospectively reviewed their first 222 consecutive patients with clinically localized (N0) prostate carcinoma treated with a 6‐field conformal technique from October 1993 through March 2000. Standardized target definitions, dose planning constraints, and gantry angles were utilized to develop the treatment plan. Patients were categorized by low, intermediate, and high risk. Low risk was defined as T1a–T2a disease, a Gleason score < 7, and prostate‐specific antigen (PSA) level ≤ 10.0 ng/mL (n = 47 [21%]). Intermediate risk was defined as T2b disease, a Gleason score > 6, or PSA level > 10.01 ng/mL (n = 60 [27%]). High risk was defined as 2 of the above risk factors or as T3 disease, a Gleason score > 7, or a PSA level > 20 (n = 115 [52%]). Biochemical disease recurrence was defined in accordance with the American Society for Therapeutic Radiology and Oncology definition. Urinary and bowel toxicity were graded using the Radiation Therapy Oncology Group morbidity scoring system.The median follow‐up after radiotherapy for surviving patients was 47 months (range, 0–99 months). The 2 and 5‐year actuarial biochemical control rates for all patients were 84% and 78%, respectively. Using logistic regression analysis, lower dose (< 75.6 gray [Gy] vs. 75.6 Gy; P = 0.006), higher risk group (P = 0.033), higher stage (P = 0.045), and higher PSA level (P = 0.001) were significantly associated with biochemical disease recurrence. Toxicity was not significantly correlated with a higher radiotherapy dose.Dose escalation to 75.6 Gy using a 6‐field conformal technique was feasible in the authors' community practice and resulted in acceptable toxicity and early biochemical outcomes. Cancer 2004. © 2004 American Cancer Society.

Abstract: Thirty-two patients with breast abnormalities and 10 normal volunteers were examined with magnetic resonance imaging (MRI) utilizing a 0.5-Tesla superconducting magnet imaging system. Sagittal, coronal, and transverse breast imaging with the 50-cm body coil and with a specialized 168 cm breast coil allowed the evaluation of a single breast. Soft-tissue contrast was clearly apparent using proton density-weighted. T1 weighted, calculated T1 images. In addition, the feasibility and potential clinical utility of three-dimensional color imaging was evaluated using computer-based interactive algorithms for edge detection of the breast and for abnormal structures within the breast. MR scan data were correlated with conventional xeromammography, ultrasound, clinical, data, and pathological specimens. In vivo and in vitro breast imaging was evaluated in a feasibility study. It was concluded that MR imaging is a most sensitive modality for the identification of breast lesions, especially when the adjacent normal tissue is primarily fat. There does appear to be significant overlap in soft-tissue contrast when the adjacent breast parenchymal tissue is fibrocystic in nature. The T1 parameter may be a relatively specific measure for identifying a malignant breast mass.

Intracellular glutathione (GSH) concentrations were titrated in Chinese hamster ovary cells by exposure to various concentrations of diethylmaleate (DEM). The various steady state levels of GSH obtained were maintained throughout the experimental time course. Cells were incubated at 42° after DEM addition in order to produce thermal dose response curves using colony formation as the end point. The slope of the dose response curve was subsequently determined and compared to the intracellular GSH concentration. This comparison indicated Chinese hamster ovary cells contain multiple reservoirs of GSH which in turn regulate thermal toxicity in a stepwise manner. Removal of 50% or less of the GSH did not affect thermal sensitivity. A small increase in sensitivity occured when 50 to 80% of the GSH was removed. Removal of greater than 80% of the GSH increased thermal toxicity significantly. The facts that 10 and 20 µM DEM produce extensive GSH depletion and only small changes in survival imply that a threshold concentration of GSH must be removed before thermal toxicity is affected.