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Biomedical subjects

I Dennis

Publications and source records attributed to I Dennis.

4 recordsLinked to original sources
PubMed1992

Phase I study of BW12C in combination with mitomycin C in patients with advanced gastrointestinal cancer.

The effect of combining the oxyhemoglobin-modifying drug BW12C with mitomycin C was investigated in a Phase I study of 18 patients with advanced gastrointestinal cancer. The dose of BW12C was increased from 20 mg/kg to 50 mg/kg to modify the hemoglobin-oxygen saturation curve by up to 48%. The period of maximum modification was then prolonged for up to 3 hr by a maintenance infusion of 4-6 mg/kg/hr. Pharmacokinetics of BW12C and mitomycin C were performed in all patients. Peak levels of BW12C increased from 139 micrograms/ml to 378 micrograms/ml. Plasma half life was independent of dose, with an average of 3.3 hr. BW12C was well tolerated with no severe side effects. Three patients had objective tumour responses.

Adenocarcinoma↗
PubMed1992

Tumour concentrations of flavone acetic acid (FAA) in human melanoma: comparison with mouse data.

Flavone acetic acid (FAA) showed impressive effects against murine solid tumours but no activity in clinical studies. The mechanism of action in mice may involve damage to tumour vasculature or immunomodulation, and these effects may be species-specific. Alternatively, concentrations of FAA achieved in mouse tumours may be higher than in human tumours. It is important to resolve this issue since it raises important questions about the relevance of in vitro versus in vivo tumour screens and the development of FAA analogues. As part of a Cancer Research Campaign Phase II study of metastatic melanoma in which 8.4 g m-2 FAA was given as a 6 h infusion, six tumour biopsies were obtained from four patients. FAA tumour concentrations were determined by HPLC and compared with subcutaneous murine solid tumours within the same analytical laboratory. Tumour/plasma percentages (range 26-61%; mean +/- SD, 43.9 +/- 11.4%) were similar to those in mice, as was the area under the curve (AUC) extrapolated to infinity and the AUC above the putative activity threshold of 100 micrograms ml-1. We conclude that the exposure of drug-refractory human melanoma tissue to FAA was comparable to that of sensitive mouse tumours. This suggests that reduced penetration of FAA into human tumours is unlikely to explain the lack of antitumour activity observed in clinical studies and that differences in mechanism of action are predominant.

Adult↗
PubMed1991

Improving auditory warning design: relationship between warning sound parameters and perceived urgency.

This paper presents an experimental study of the effects of individual sound parameters on perceived (psychoacoustic) urgency. Experimental Series 1 showed that fundamental frequency, harmonic series, amplitude envelope shape, and delayed harmonics all have clear and consistent effects on perceived urgency. Experimental Series 2 showed that temporal and melodic parameters such as speed, rhythm, pitch range, and melodic structure also have clear and consistent effects on perceived urgency. The final experiment tested a set of 13 auditory warnings generated by an application of the earlier experimental findings. The urgency rank ordering of this warning set was predicted, and the correlation between the predicted and the obtained order was highly significant. The results of these experiments have a widespread application in the improvement of existing auditory warning systems and the design of new systems, where the psychoacoustic and psychological appropriateness of warnings could be enhanced.

Accidents, Occupational↗