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The antitumour action of 5,6-dimethylxanthenone-4-acetic acid (DMXAA) is mediated through tumour-selective antivascular effects and cytokine induction. This clinical phase I trial was conducted to examine its toxicity, maximum tolerated dose, pharmacokinetics (PK) and pharmacodynamics (PD). A secondary objective was to assess its antitumour efficacy. DMXAA was administered every 3 weeks as a 20-min i.v. infusion. Dose escalation initially followed a modified Fibonacci schema but was also guided by PK and toxicity. A total of 63 patients received 161 courses of DMXAA over 19 dose levels ranging from 6 to 4900 mg m(-2). DMXAA was well tolerated at lower doses and no drug-related myelosuppression was seen. Rapidly reversible dose-limiting toxicities were observed at 4900 mg m(-2), including confusion, tremor, slurred speech, visual disturbance, anxiety, urinary incontinence and possible left ventricular failure. Transient prolongation of the corrected cardiac QT interval was seen in 13 patients evaluated at doses of 2000 mg m(-2) and above. A patient with metastatic cervical carcinoma achieved an unconfirmed partial response at 1100 mg m(-2), progressing after eight courses. The results of PK and PD studies are reported separately. DMXAA has antitumour activity at well-tolerated doses. [ABSTRACT FROM AUTHOR]

Background: Wine appears to be a significant trigger for asthma. Although sulfite additives have been implicated as a major cause of wine induced asthma, direct evidence is limited. Two studies were undertaken to assess sulfite reactivity in wine sensitive asthmatics. The first study assessed sensitivity to sulfites in wine using a single dose sulfited wine challenge protocol followed by a double blind, placebo controlled challenge. In the second study a cumulative dose sulfited wine challenge protocol was employed to establish if wine sensitive asthmatics as a group have an increased sensitivity to sulfites.Methods: In study 1, 24 asthmatic patients with a strong history of wine induced asthma were screened. Subjects showing positive responses to single blind high sulfite (300 ppm) wine challenge were rechallenged on separate days in a double blind, placebo controlled fashion with wines of varying sulfite levels to characterise their responses to these drinks. In study 2, wine sensitive asthmatic patients (n=12) and control asthmatics (n=6) were challenged cumulatively with wine containing increasing concentrations of sulfite in order to characterise further their sensitivity to sulfites in wine.Results: Four of the 24 self-reporting wine sensitive asthmatic patients were found to respond to sulfite additives in wine when challenged in a single dose fashion (study 1). In the double blind dose-response study all four had a significant fall in forced expiratory volume in one second (FEV(1)) (>15% from baseline) following exposure to wine containing 300 ppm sulfite, but did not respond to wines containing 20, 75 or 150 ppm sulfite. Responses were maximal at 5 minutes (mean (SD) maximal decline in FEV(1) 28.7 (13)%) and took 15-60 minutes to return to baseline levels. In the cumulative dose-response study (study 2) no significant difference was observed in any of the lung function parameters measured (FEV(1), peak expiratory flow (PEF), mid phase forced expiratory flow (FEF(25-75))) between wine sensitive and normal asthmatic subjects.Conclusions: Only a small number of wine sensitive asthmatic patients responded to a single dose challenge with sulfited wine under laboratory conditions. This may suggest that the role of sulfites and/or wine in triggering asthmatic responses has been overestimated. Alternatively, cofactors or other components in wine may play an important role in wine induced asthma. Cumulative sulfite dose challenges did not detect an increased sensitivity to sulfite in wine sensitive asthmatics and an alternative approach to identifying sulfite/wine sensitive asthma may be required. [ABSTRACT FROM AUTHOR]

Background: Robust data on patient-reported outcome measures comparing treatments for clinically localized prostate cancer are lacking. We investigated the effects of active monitoring, radical prostatectomy, and radical radiotherapy with hormones on patient-reported outcomes.Methods: We compared patient-reported outcomes among 1643 men in the Prostate Testing for Cancer and Treatment (ProtecT) trial who completed questionnaires before diagnosis, at 6 and 12 months after randomization, and annually thereafter. Patients completed validated measures that assessed urinary, bowel, and sexual function and specific effects on quality of life, anxiety and depression, and general health. Cancer-related quality of life was assessed at 5 years. Complete 6-year data were analyzed according to the intention-to-treat principle.Results: The rate of questionnaire completion during follow-up was higher than 85% for most measures. Of the three treatments, prostatectomy had the greatest negative effect on sexual function and urinary continence, and although there was some recovery, these outcomes remained worse in the prostatectomy group than in the other groups throughout the trial. The negative effect of radiotherapy on sexual function was greatest at 6 months, but sexual function then recovered somewhat and was stable thereafter; radiotherapy had little effect on urinary continence. Sexual and urinary function declined gradually in the active-monitoring group. Bowel function was worse in the radiotherapy group at 6 months than in the other groups but then recovered somewhat, except for the increasing frequency of bloody stools; bowel function was unchanged in the other groups. Urinary voiding and nocturia were worse in the radiotherapy group at 6 months but then mostly recovered and were similar to the other groups after 12 months. Effects on quality of life mirrored the reported changes in function. No significant differences were observed among the groups in measures of anxiety, depression, or general health-related or cancer-related quality of life.Conclusions: In this analysis of patient-reported outcomes after treatment for localized prostate cancer, patterns of severity, recovery, and decline in urinary, bowel, and sexual function and associated quality of life differed among the three groups. (Funded by the U.K. National Institute for Health Research Health Technology Assessment Program; ProtecT Current Controlled Trials number, ISRCTN20141297 ; ClinicalTrials.gov number, NCT02044172 .). [ABSTRACT FROM AUTHOR]

Interactions between phenytoin and the fluoropyrimidine derivatives, 5 fluorouracil (5FU) and capecitabine, are not commonly documented or widely recognised. As more people with significant medical comorbidities are now being considered for chemotherapy, it is increasingly likely that people receiving phenytoin will be prescribed treatment with fluoropyrimidines. We present two cases of clinical phenytoin toxicity occurring after starting treatment with 5-fluorouracil/folinic acid (5FU/FA) and a third who developed clinical phenytoin toxicity after starting capecitabine (an orally administered prodrug of fluorouracil). [ABSTRACT FROM AUTHOR]

Within a stereoscopic display the field of view (FOV) was held constant at 13.86 degrees while the geometric field of view (GFOV) was varied across four levels: 0 degrees (parallel), 13.86 degrees (veridical), 50 degrees and 100 degrees. Participants performed a distance-matching task where they adjusted the distance of a standard track from the centre of the display to match the distance of a target track from the same point. The results indicated that while the least error occurred in the veridical GFOV condition, small variations of GFOV away from the veridical have little effect. Large differences between FOV and GFOV (36 degrees and 86 degrees) increased errors markedly. A trend toward better performance in the veridical GFOV condition relative to the parallel GFOV condition suggests that the use of linear perspective information in a stereoscopic display may facilitate more accurate spatial perception. Actual or potential applications of this work include stereoscopic display design in aviation and non-aviation settings. [ABSTRACT FROM AUTHOR]

Objective: People with schizophrenia exhibit abnormalities in brain structure, often in the left hemisphere. Disturbed structural lateralization is controversial, however, and effects appear mediated by gender. The authors mapped differences between schizophrenic and normal subjects in gyral asymmetries, complexity, and variability across the entire cortex.Method: Asymmetry and shape profiles for 25 schizophrenic patients (15 men) and 28 demographically similar normal subjects (15 men) were obtained for 38 gyral regions, including the sylvian fissure and temporal and postcentral gyri, by using magnetic resonance data and a novel surface-based mesh-modeling approach. Cortical complexity was examined for sex and diagnosis effects in lobar regions. Intragroup variability was quantified and visualized to assess regional group abnormalities at the cortical surface.Results: The patients showed greater variability in frontal areas than the comparison subjects. They also had significant deviations in gyral complexity asymmetry in the superior frontal cortex. In temporoparietal regions, significant gyral asymmetries were present in both groups. Sex differences were apparent in superior temporal gyral measures, and cortical complexity in inferior frontal regions was significantly greater in men.Conclusions: Cortical variability and complexity show regional abnormalities in the frontal cortex potentially specific to schizophrenia. The results indicate highly significant temporoparietal gyral asymmetries in both diagnostic groups, contrary to reports of less lateralization in schizophrenia. Substantially larger study groups are necessary to isolate smaller deviations in surface asymmetries, if present in schizophrenia, suggesting their diagnostic value is minimal. [ABSTRACT FROM AUTHOR]

Financial incentives of various kinds have been suggested to alleviate the chronic shortage of transplantable organs in the United States. This paper analyzes the possible consequences of financial incentives on organ supply. We show that under current practice and current law (which are not the same), inducements to donate organs or to register as an organ donor may lead to a decline in the supply of organs. Furthermore, some financial incentives that have been proposed lead to time inconsistent choices. [ABSTRACT FROM AUTHOR]

Oral anabolic steroids produce striking reductions in serum concentrations of high-density lipoprotein (HDL) cholesterol. We hypothesized that this effect related to their route of administration and was unrelated to their androgenic potency. We administered oral stanozolol (6 mg/d) or supraphysiological doses of intramuscular testosterone enanthate (200 mg/wk) to 11 male weight lifters for six weeks in a crossover design. Stanozolol reduced HDL-cholesterol and the HDL2 subfraction by 33% and 71%, respectively. In contrast, testosterone decreased HDL-cholesterol concentration by only 9% and the decrease was in the HDL3 subfraction. Apolipoprotein A-I level decreased 40% during stanozolol but only 8% during testosterone treatment. The low-density lipoprotein cholesterol concentration increased 29% with stanozolol and decreased 16% with testosterone treatment. Stanozolol, moreover, increased postheparin hepatic triglyceride lipase activity by 123%, whereas the maximum change during testosterone therapy (+25%) was not significant. Weight gain was similar with both drugs, but testosterone was more effective in suppressing gonadotropic hormones. We conclude that the undesirable lipoprotein effects of 17-alpha-alkylated steroids given orally are different from those of parenteral testosterone and that the latter may be preferable in many clinical situations. [ABSTRACT FROM AUTHOR]

Focuses on the result of a study on cancer data collected during 1971 to 2001 conducted by the National Cancer Institute and the Centers for Disease Control. Information on cancer survivors; Overview of the report; Process of conducting the study.