Continued development of the Nimbus/University of Pittsburgh (UOP) axial flow left ventricular assist system

Nimbus and the University of Pittsburgh (UOP) have continued the development of a totally implanted axial flow blood pump under the National Institutes of Health (NIH) Innovative Ventricular Assist System (IVAS) program. This 62 cc device has an overall length of 84 mm and an outer diameter of 34.5 mm. The inner diameter of the blood pump is 12 mm. It is being designed to be a totally implanted permanent device. A key achievement during the past year was the completion of the Model 2 pump design. Ten of these pumps have been fabricated and are being used to conduct in vitro and in vivo experiments to evaluate the performance of different materials and hydraulic components. Efforts for optimizing the closed loop speed control have continued using mathematical modeling, computer simulations, and in vitro and in vivo testing. New hydraulic blade designs have been tested using computational fluid dynamics (CFD) and flow visualization. A second generation motor was designed with improved efficiency. To support the new motor, a new motor controller fabricated as a surface mount PC board has been completed. The program is now operating under a formal QA system.     

Patient-specific predictions for clinical decision-making

There are many ways in which clinicians make decisions regarding therapy for an individual patient. Invariably, the decision is supplemented by collateral information which is obtained from clinical trials. Prospective and retrospective clinical studies take an unnecessary adversarial position but each method has its place. Parametric survival analysis can produce patient-specific predictions of an event of interest for an individual patient based on the risk factor profile of that patient, and these methods are just as applicable to prospective clinical studies as they are to retrospective clinical studies. Parametric survival analysis can estimate the distribution of time to an event, estimate the phases of hazard (instantaneous risk of the event), determine risk factors associated with the event in each of the identified phases of risk, predict the time-related probability of an event for a specific patient based on his or her risk factor profile, and by risk adjustment compare the effectiveness of different therapies.     

Iodized oil enhances the thermal effect of high-intensity focused ultrasound on ablating experimental liver cancer

The influence of the biological medium on high-intensity focused ultrasound (HIFU) therapy for ablating experimental liver cancer was studied. In study 1, the temperature rise in the focal zone in the presence of iodized oil or castor oil was observed in vitro. The results showed that HIFU with iodized oil produced a higher and faster temperature rise than did HIFU with castor oil, whether high-power (500 W/cm2) or relatively low-power (136 W/cm2) conditions were used (P = 0.0008 and P = 0.0004 respectively). With the excised liver samples, the temperature also rose higher and more rapidly after injection of iodized oil into the liver than when castor oil was injected (P = 0.0239), and the target liver tissue revealed more radically and extensive destruction with iodized oil than with castor oil. In study 2, 48 nude mice, bearing primary liver cancer LTNM4 implanted subcutaneously, were randomly divided into four groups. Group I (n = 12) were the controls, group II (n = 12) were injected with iodized oil alone, group III (n = 12) received HIFU treatment, and group IV (n = 12) were exposed to HIFU after iodized oil injection. Significant inhibition of tumor growth was seen in groups III and IV as compared with group I or group II (P < 0.05), the tumor growth inhibition rate on the 28th day after treatment being 87% and 93% respectively. Significantly improved survival was noted in groups III and IV compared with groups I and II (P < 0.05). Histologically, group IV showed more complete tumor necrosis than did group III. These data suggest that HIFU combined with iodized oil might have achieve of synergism, location and targeting in the treatment of liver cancer.     

Nationwide survey of fluoroscopy: radiation dose and image quality

PURPOSE: To determine the average abdominal entrance air kerma, low-contrast sensitivity, and spatial resolution in upper gastrointestinal tract fluoroscopy in the United States. MATERIALS AND METHODS: A random sample of fluoroscopic facilities was selected to be surveyed for the Nationwide Evaluation of X-ray Trends program. Measurements were performed by using a newly developed fluoroscopic phantom. The surveys were conducted by state radiation control personnel. RESULTS: Average air kerma rates 1 cm above the tabletop, free in air, were 43 mGy/min (n = 340). The rate increased to 64 mGy/min when a 1.6-mm-thick copper filter, which simulated the use of barium contrast medium, was added to increase attenuation. The average entrance air kerma, free in air, for radiographs was 3.4 mGy, and an average of 12 radiographs were obtained per examination. Of 352 facilities surveyed, 306 (87%) were able to resolve wire mesh with 20 or more lines per inch. Of 339 facilities for which percentage contrast could be calculated, 192 (57%) had minimum percentage contrast values of 4% or more. CONCLUSION: Spatial resolution for fluoroscopy is adequate for most of the facilities surveyed, but a substantial proportion of facilities could not visualize low-contrast test objects, which strongly suggests image quality problems.     

Homocamptothecins: synthesis and antitumor activity of novel E-ring-modified camptothecin analogues

Homocamptothecin (hCPT), a camptothecin (CPT) analogue with a seven membered beta-hydroxylactone which combines enhanced plasma stability and potent topoisomerase I (Topo I)-mediated activity, is an attractive template for the elaboration of new anticancer agents. Like CPT, hCPT carries an asymmetric tertiary alcohol and displays stereoselective inhibition of Topo I. The preparation and biological screening of racemic hCPT analogues are described. The 10 hCPTs tested were better Topo I inhibitors than CPT. Fluorinated hCPTs 23c, d,f,g were found to have potent cytotoxic activity on A427 and PC-3 tumor cell lines. Their cytotoxicity remained high on the K562adr and MCF7mdr cell lines, which overexpress a functionally active P-glycoprotein. Fluorinated hCPTs were more efficacious in vivo than CPT on HT-29 xenografts. In this model, a tumor growth delay of 25 days was reached with hCPT 23g at a daily dose of 0.32 mg/kg, compared to 4 days with CPT at 0.625 mg/kg. Thus difluorinated hCPT 23g warrants further investigation as a novel Topo I inhibitor with high cytotoxicity toward tumor cells and promising in vivo efficacy.     

Angiographically defined primary angiitis of the CNS: is it really benign?

Children with B-progenitor cell acute lymphoblastic leukemia whose lymphoblasts at diagnosis accumulate high levels of methotrexate (MTX) and MTX polyglutamates (MTXPGs) appear to have a good prognosis. This has been attributed to increased sensitivity of their blast cells to MTX. However, the proportion of children who are cured of B-progenitor cell acute lymphoblastic leukemia exceeds the number whose lymphoblasts accumulate high MTXPG levels. We report that lymphoblasts from patients with < 50 chromosomes who have translocations that involve the short arm of chromosome 12 accumulate low levels of MTXPGs. These patients appear to have an excellent survival because none of 14 patients with translocations affecting 12p has relapsed, 26-79 months following diagnosis.     

Lymphoma cell burden in progenitor cell grafts measured by competitive polymerase chain reaction: less than one log difference between bone marrow and peripheral blood sources

The suppressor of Hairy-wing [SU(HW)] binding region disrupts communication between a large number of enhancers and promoters and protects transgenes from chromosomal position effects. These properties classify the SU(HW) binding region as an insulator. While enhancers are blocked in a general manner, protection from repressors appears to be more variable. In these studies, we address whether repression resulting from the Polycomb group genes can be blocked by the SU(HW) binding region. The effects of this binding region on repression established by an Ultrabithorax Polycomb group Response Element were examined. A transposon carrying two reporter genes, the yellow and white genes, was used so that repression and insulation could be assayed simultaneously. We demonstrate that the SU(HW) binding region is effective at preventing Polycomb group repression. These studies suggest that one role of the su(Hw) protein may be to restrict the range of action of repressors, such as the Polycomb group proteins, throughout the euchromatic regions of the genome.