Citations

Multi-frequency signals were transmitted using a plane-wave transducer, through a water immersed phantom consisting of two finger cots, one containing 50% isopropanol alcohol and the other containing normal saline. The scattered ultrasound was received with a small hydrophone and detected with a quadrature detection system. The resulting phase quadrature data were submitted to a reconstruction algorithm which utilized the Rytov approximation to the Helmholtz equation in order to obtain the inverse solution for the distribution of refraction index within the phantom. In one experiment pseudo-random noise was generated by loading a 256 by 8-bit memory with random numbers and then synchronously reading these values through a D/A converter into an EMI power amplifier which drove the plane-wave transducer. The data received from each of 60 angles of view were spectral analyzed and specific frequencies selected for the cw reconstruction algorithm. Multiple frequency reconstructions will be shown as will the effect of frequency on the various underlying assumptions for the approximation. [Supported in part by Grants CA 24085 and NCI and ECS 7296008 from NSF.]

Purpose Contralateral prophylactic mastectomy (CPM) is one option for reducing the risk of a second breast cancer in women with a personal and family history of breast cancer. Few data are available regarding satisfaction, psychological, and social function after CPM. The purpose of this research is to evaluate women’s long-term satisfaction with CPM, factors influencing satisfaction, and psychological and social function after CPM. Patients and Methods This was a descriptive study of all women with a family history of breast cancer, known to be alive, who elected CPM at Mayo Clinic (Rochester, MN) between 1960 and 1993 (n = 621). Ninety-four percent of the women (n = 583) completed a study-specific questionnaire. Results A mean of 10.3 years after the procedure, the majority of women (83%) were satisfied with their CPM. A smaller number were neutral (8%) or dissatisfied (9%). Women who had a subcutaneous mastectomy had more problems with reconstruction, and fewer of these women were satisfied than women with simple mastectomy. Decreased satisfaction with CPM was associated with decreased satisfaction with appearance, complications with reconstruction, reconstruction after CPM, and increased level of stress in life. The majority of women experienced no change or favorable effects in self-esteem (83%), level of stress in life (83%), and emotional stability (88%). Satisfaction with body appearance, feelings of femininity, and sexual relationships were the most adversely affected with 33%, 26%, and 23% of the women responding negatively. Conclusion Although most women are satisfied with CPM, each woman should weigh the benefits alongside the potential adverse effects.

Data and simulated data from circumscribing and linear sampled arrays has been used to form high resolution reflection images by two techniques. The first technique (synthetic focusing) uses the mathematical equivalent of a lense to focus the image at each point by adding either linear (uncompressed) or nonlinear (compressed) transforms of the data. Logarithmic and square root compression is studied. The lense effect is obtained by backprojecting convolved or other linear transformed versions of the data along equal time propagation surfaces in the image with appropriate corrections for refraction and frequency dependent attenuation. The choice of apodizing function and different wave forms can greatly improve image resolution. The second technique (reflection ART) is not based on a focusing model but rather on direct inversion of a matrix (linear transform) model of the object-acoustic field interaction and data acquisition process by a Kacmarz iterative inversion method. The two methods are compared.

Quantitative images of acoustic speed distribution in excised human tissues, in excised dog myocardium, and in in vivo female breasts were obtained by ultrasound computerized tomography. The in vitro study was carried over a temperature from 20° to 40 °C. Results indicate (1) acoustic speed in human tissues (except fat) increase monotonically with temperature in this range, (2) fat shows an anomalous decrease in acoustic speed around 35 °C, (3) average acoustic speed is higher in breasts with cancer and with fibrocystic disease compared to normal breasts, and (4) acoustic speed is a function of age. The reconstruction problem in ultrasound computerized tomography is unlike its x-ray analog because of the refraction and diffraction effects. Methods to correct for the consequent degradation are discussed. The backscattering properties of in vivo myocardial tissue of dogs were studied by a high-resolution B-scanner and the potential of (renovist and indocyanine green) as ultrasound contrast agents to quantitate perfusion in the myocardium will be discussed. [Work supported by NCI-CB-64041, HV 72928, HL-07111, HL-00060, HL-00170.]

Abstract Protein kinase C (PKC) isozymes have long been implicated in carcinogenesis. However, little is known about the functional significance of these enzymes in human cancer. We recently showed that the atypical PKC (aPKC) isozyme PKCι is overexpressed in human non–small cell lung cancer (NSCLC) cells and that PKCι plays a critical role in the transformed growth of the human lung adenocarcinoma A549 cell line in vitro and tumorigenicity in vivo. Here we provide compelling evidence that PKCι is an oncogene in NSCLC based on the following criteria: (a) aPKCι is overexpressed in the vast majority of primary NSCLC tumors; (b) tumor PKCι expression levels predict poor survival in patients with NSCLC; (c) the PKCι gene is frequently amplified in established NSCLC cell lines and primary NSCLC tumors; (d) gene amplification drives PKCι expression in NSCLC cell lines and primary NSCLC tumors; and (e) disruption of PKCι signaling with a dominant negative PKCι allele blocks the transformed growth of human NSCLC cells harboring PKCι gene amplification. Taken together, our data provide conclusive evidence that PKCι is required for the transformed growth of NSCLC cells and that the PKCι gene is a target for tumor-specific genetic alteration by amplification. Interestingly, PKCι expression predicts poor survival in NSCLC patients independent of tumor stage. Therefore, PKCι expression profiling may be useful in identifying early-stage NSCLC patients at elevated risk of relapse. Our functional data indicate that PKCι is an attractive target for development of novel, mechanism-based therapeutics to treat NSCLC.

Background— The goal of this study was to determine whether the expression of vascular endothelial growth factor (VEGF) is critical for coronary collateral growth. Previous studies have provided an association between coronary collateral growth and VEGF, but none have allowed determination of a causal role. Methods and Results— We measured coronary collateral growth in rats subjected to repetitive episodes of myocardial ischemia (RI; one 40-second occlusion every 20 minutes for 2 hours 40 minutes, followed by 5 hours 20 minutes of rest, with this 8-hour cycle repeated 3 times per day for 10 days). Collateral growth was measured from blood flow (radioactive microspheres), visualization of arterial-arterial anastomoses (x-ray micro-CT), and maintenance of function during complete coronary occlusion in 3 groups of animals: sham (received instrumentation but no RI), experimental (subjected to RI), and anti–vascular endothelial growth factor (RI+anti-VEGF 0.6 mg/100 g per day) to block the endogenous actions of VEGF. In the 3 groups, native collateral flow (measurement for RI or sham protocol) averaged 0.2 to 0.3 mL · min −1 · g −1 of tissue. In the sham group, collateral flow did not increase during the protocol. Collateral flow in the control RI group increased by ≈6-fold to 1.63 mL · min −1 · g −1 tissue, but in the anti-VEGF group, collateral flow did not increase after the RI protocol (0.22 mL · min −1 · g −1 ). In acute experiments, collateral flow was unchanged during vasodilation with dipyridamole, indicating the increases in collateral flow are due to collateral growth and not vasodilation. X-ray micro-CT analysis revealed a 3-fold increase (versus sham group) in the number of arterial-arterial anastomoses per heart after RI, which was prevented by treatment with anti-VEGF. The growth of the collateral circulation was functional in the RI group because complete coronary occlusion did not induce any untoward effects on hemodynamics or arrhythmias. In the sham or anti-VEGF groups, coronary occlusion at the end of the protocol induced many arrhythmias and deterioration of function. Conclusions— From these results, we conclude that the expression of VEGF is critical to the growth of coronary collaterals.

Background— Increases in vascular (Ea), ventricular systolic (Ees), and ventricular diastolic (Ed) elastance (stiffness) may contribute to the pathogenesis of heart failure (HF) with preserved ejection fraction (HFnlEF). The prevalence of HFnlEF increases strikingly with age, particularly in women. We hypothesized that ventricular-vascular stiffening may occur with age and be more pronounced in women in the general community. Methods and Results— In a cross-sectional sample of Olmsted County, Minn, residents ≥45 years old (n=2042), clinical data, Doppler echocardiography, and blood pressure (BP) measurements were obtained. Ea was calculated from stroke volume and systolic BP and indexed to body size (EaI). Ees was calculated by a modified single-beat method using systolic and diastolic BP, stroke volume, ejection fraction, timing intervals, and an estimated normalized ventricular elastance at arterial end diastole. Operant Ed was calculated from Doppler indices reflective of atrial pressures and the diastolic filling volume. EaI, Ees, and Ed all increased with age in men and in women ( P <0.0001 for all). Ees increased more steeply with age in women ( P =0.002). Adjusted for age, EaI, Ees, and Ed were higher in women than in men ( P <0.0001 for all). Findings were similar in those without known or suspected cardiovascular disease (n=623). Conclusions— In the community, advancing age and female gender are associated with increases in vascular and ventricular systolic and diastolic stiffness even in the absence of cardiovascular disease. We speculate that this combined ventricular-vascular stiffening may contribute to the increased prevalence of HFnlEF in elderly persons and particularly in elderly women.

Policy has not adequately addressed the unique circumstances of pediatric subspecialties, many of which are facing workforce shortages. Pediatric subspecialties, which we define to include all medical and surgical subspecialties, are discrete disciplines that differ significantly from each other and from adult medicine subspecialties. Concerns about a current shortage of pediatric subspecialists overall are driven by indicators ranging from recruitment difficulties to long wait times for appointments. The future supply of pediatric subspecialists and patient access to pediatric subspecialty care will be affected by a number of key factors or forces for change. We discuss 5 of these factors: changing physician and patient demographics; debt load and lifestyle considerations; competition among providers of subspecialty care; equitable reimbursement for subspecialty services; and policy to regulate physician supply. We also identify issues and strategies that medical and specialty societies, pediatric subspecialists, researchers, child advocates, policy makers, and others should consider in the development of subspecialty-specific workforce-policy agendas.