Biochemical modulation in the treatment of advanced cancer: a study of combined leucovorin, fluorouracil, and iododeoxyuridine

Multiple studies have shown that leucovorin-fluorouracil regimens are modestly superior to fluorouracil alone in the treatment of advanced colorectal cancer. Laboratory data suggest that iododeoxyuridine could further enhance the efficacy of leucovorin-fluorouracil regimens. This report describes the Phase I clinical evaluation of a leucovorin-fluorouracil-iododeoxyuridine chemotherapy regimen. Twenty-four patients received treatment with leucovorin (500 mg/m2), fluorouracil (500 mg/m2), and iododeoxyuridine (escalating doses) on days 1 and 8 of a 21-day cycle. The maximum tolerated dose of iododeoxyuridine was 1200 mg/m2, with a recommended Phase II dose of 1000 mg/m2. Myelosuppression (leukopenia) was dose limiting; other commonly observed treatment toxicities were nausea/vomiting, mucositis, and hyperlacrimation. Although the 1200 mg/m2 dose was tolerated during the initial few cycles of therapy, chronic administration could not be maintained secondary to dose-limiting neutropenia. Since neutropenia was dose limiting, in a follow-up study, 10 patients received a modified regimen (treatment on days 1 and 6 instead of days 1 and 8) with the addition of granulocyte colony-stimulating factor (days 8-19). The addition of granulocyte colony-stimulating factor, however, did not permit further escalation of the iododeoxyuridine dose. Three partial responses and six minor responses were observed. Phase II studies of this regimen are ongoing in advanced colorectal and advanced pancreatic cancer to determine response rates in these diseases.     

The West Wing as Endorsement of the U.S. Presidency: Expanding the Bounds of Priming in Political Communication

This study uses priming as a theoretical basis from which to investigate potential effects of NBC's The West Wing on individual-level perceptions of the U.S. presidency. As a result, this work extends political communication-based priming research to entertainment television content. Josiah Bartlet, the fictional president portrayed on the show, is generally perceived more positively by viewers than either the Republican President George W. Bush or Democrat William Jefferson Clinton. Perceptions of the importance of being engaging to presidential success rose as a result of watching the program, and The West Wing viewers retained more positive images of Bush and Clinton after the viewing experience. Viewing The West Wing seems to prime more positive images of the U.S. presidency that subsequently influence individual-level perceptions of those individuals most directly associated with this office. The authors make theoretical connections to previous work on role display and trust in democratic institutions.     

0.125% ropivacaine is similar to 0.125% bupivacaine for labor analgesia using patient-controlled epidural infusion

In order to assess the lifetime risk of skin cancer for recreational users from dermal exposure to polycyclic aromatic hydrocarbons (PAHs), sediment samples were collected from beach sites along the St. Marys River near Sault Ste. Marie, Ontario, and in Hamilton Harbor and Toronto Harbor, Ontario, and analyzed for PAHs. Dermal exposure and lifetime skin cancer risk were estimated as follows: Concentrations of 11 PAHs with sufficient or limited evidence of carcinogenicity or mutagenicity were converted to benzo(a)pyrene (BaP) equivalents using toxic equivalency factors (TEFs). Lifetime dermal exposure values were derived based on the BaP equivalents in the silt + clay fraction taken as representative of suspended sediment particulates to which recreational users would be exposed. The lifetime health risk of skin cancer associated with such exposures was above the negligible risk level of 1.0 x 10(-6) at offshore Rytac, Lake George Channel, and Bell Point beaches in the St. Marys River; at Pier 4 Park in Hamilton Harbor; and at Humber Bay, Sunnyside Beach, Cherry Beach, and Water Rats Sailing Club in Toronto Harbor. Risk was negligible inshore at the Rytac and Bell Point beaches and at Squirrel Island and Ojibway Trailer Park along St. Marys River, at Lax Beach in Hamilton Harbor; and at Centre Island in Toronto Harbor. Strategies to reduce risk were developed with these communities; a key recommendation was to take a bath or shower within 24 h after a swim because virtually all the PAHs on the skin would be removed.     

Homophone effects in visual word recognition depend on homophone type and task demands.

This experiment examined how the characteristics of homophones and their mates influence homophone effects, as a function of task demands. Two types of homophones were presented: 1) low-frequency homophones with higher-frequency mates that are not animal names (e.g., maid--made), and 2) low-frequency homophones with mates that are, on average, of equivalent frequency and are animal names (e.g., foul--fowl). We observed a double dissociation: In the lexical decision task (LDT), there was a homophone effect for the first type of homophones but not for the second, whereas in the semantic categorization task (SCT) the opposite was true. These results suggest that in these tasks the effects of homophony arise when the homophone's mate creates competition in terms of the type of processing emphasized in the task, namely, orthographic processing in the LDT and semantic processing in the SCT. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The affinities of procolipase and colipase for interfaces are regulated by lipids

It has been suggested that at physiological pH, the trypsin-catalyzed activation of the lipase cofactor, procolipase, to colipase has no consequence for intestinal lipolysis and serves primarily to release the N-terminal pentapeptide, enterostatin, a satiety factor (Larsson, A., and C. Erlanson-Albertsson 1991. The effect of pancreatic procolipase and colipase on pancreatic lipase activation. Biochim. Biophys. Acta 1083:283-288). This hypothesis was tested by measuring the adsorption of [14C]colipase to monolayers of 1-stearoyl-2-oleoyl-sn-3-glycerophosphocholine and 13, 16-cis, cis-docosadienoic acid in the presence and absence of procolipase. With saturating [14C]colipase in the subphase, the surface excess of [14C]colipase is 29% higher than that of procolipase, indicating that colipase packs more tightly in the interface. With [14C]colipase-procolipase mixtures, the proteins compete equally for occupancy of the argon-buffer interface. However, if a monolayer of either or both lipids is present, [14C]colipase dominates the adsorption process, even if bile salt is present in the subphase. If [14C]colipase and procolipase are premixed for > 12 h at pH approximately 8, this dominance is partial. If they are not premixed, procolipase is essentially excluded from the interface, even if procolipase is added before [14C]colipase. These results suggest that the tryptic cleavage of the N-terminal pentapeptide of procolipase may be of physiological consequence in the intestine.     

Evaluation of fetal movements as an early labour admission test in low-risk pregnancies

Fetal movements were quantified in 182 low-risk women in early labour using the Hewlett-Packard M1350A (Boblingen, Germany) fetal heart rate monitor. There were no statistically significant differences in adverse intrapartum or neonatal outcomes detected by the fetal heart rate pattern or fetal movement profile. This study confirms the feasibility of obtaining, a measure of fetal movement in early labour but does not support its use as an admission test in low-risk pregnancies.     

A comprehensive modeling environment for the simulation of groundwater flow and transport

A comprehensive graphical modeling environment has been developed to address the needs of the computer simulation of groundwater flow and transport. The Department of Defense Groundwater Modeling Systems (GMS), developed at the Engineering Computer Graphics Laboratory at Brigham Young University, is part of a multi-year project funded through the Department of Defense, Department of Energy and Environmental Protection Agency. GMS is a graphically based software tool providing facility through all aspects of the groundwater flow and transport modeling process. Facilities include geometric modeling of hydrostratigraphy, two- and three-dimensional mesh generation, graphically based model input for specific flow and transport codes, interpolation and geostatistics as well as complete three-dimensional scientific visualization.     

How healthy are the police? A survey of life-style factors

AIMS: To examine the prevalence of five life-style behaviours among New South Wales police. DESIGN: A cross-sectional survey using a self-administered questionnaire. SETTING AND PARTICIPANTS: A total of 852 police were recruited from metropolitan Sydney. MEASUREMENTS: Prevalence related to age and sex of self-reported alcohol consumption, cigarette smoking, inadequate exercise, perception of overweight and stress symptoms. RESULTS: A high level (89%) of participation was achieved in the survey. Almost half (48%) of males and more than two-fifths (40%) of females consumed alcohol excessively including continuous hazardous or harmful consumption and binge drinking. Excessive drinking was more prevalent among younger police. There were 8% of male and 15% of female police who reported that they did not drink alcohol. Over one-quarter (27%) of male and one-third (32%) of female respondents reported smoking. Almost half (46%) of men and women (47%) believed that they were overweight. More than one-fifth (21%) of men and less than one-quarter (24%) of women reported that they did not exercise. Finally, 12% of men and 15% of women reported feeling moderate to severe symptoms of stress. CONCLUSIONS: The police work-force offers an opportunity to screen for a large number of healthy, young and high risk individuals (particularly men) who are hard to reach in other settings and who rarely visit their general practitioner. A sizeable majority (83%) of NSW police had at least one unhealthy life-style behaviour with 19% reporting 3-5 unhealthy factors. The high prevalence of excessive alcohol consumption among police is of particular concern. More active health promotion and provision of brief interventions among police may reduce morbidity and mortality associated with unhealthy life-styles.     

M cells as portals of entry for HIV

Accumulating evidence points toward active uptake by mucosal antigen sampling cells as the mechanism for rectal HIV acquisition. Organized lymphoid tissue in the intestine consists of lymphoid follicles with an epithelium containing M cells specialized for uptake and transport of microorganisms, bringing them into contact with lymphoid cells. M cells have been found in the human colon and rectum, and adherence and uptake of HIV by M cells in mouse and rabbit Peyer's patches has been demonstrated in vitro. In an in vivo mouse model of viral acquisition, reovirus is actively taken up by M cells into rectal lymphoid tissue containing CD4 lymphocytes and macrophages, which are targets and replication sites for HIV. Immunization strategies for prevention of HIV transmission should include a mucosal component to prevent initial entry, since elimination from cellular sanctuaries remains an elusive goal.     

Time resolved second harmonic generation studies of double layer reorganization: sulfate adsorption and desorption on a polycrystalline silver electrode

The kinetics of the adsorption and desorption of non-specifically adsorbed anions on polycrystalline Ag electrodes biased within the limits of the ideally polarisable region have been investigated using time resolved second harmonic generation. The transient SH intensity directly correlates with the time and potential dependent surface charge density on the electrode. Attempts to fit the temporal data with existing theoretical models were unsuccessful and suggest the need for more detailed models.