Summary and conclusionsAn 11-week crossover study was carried out in which 12 subjects smoked high-nicotine (1-84 mg standard yield) and low-nicotine (0-6 mg) cigarettes after an initial period of smoking their usual brands with a medium-nicotine yield (mean 1-4 mg). Plasma and urine nicotine concentrations, carboxyhaemoglobin (COHb) concentration, puffing behaviour, 24-hour cigarette consumption, and butt nicotine content were measured. The changes in plasma nicotine and blood COHb concentrations showed that the smokers compensated for about two-thirds of the difference in standard yields when switched to either high-or low-nicotine cigarettes. Thus, compared with the medium-nicotine brand, the intake of nicotine and carbon monoxide was only about 10% higher when subjects smoked the high-nicotine cigarettes, which had a standard yield 30-40% higher than the medium brands; and only about 15% lower when they smoked the lownicotine cigarettes, which had a standard yield about 50% lower than the medium brands. Butt nicotine content and urine nicotine concentrations followed a similar pattern. Changes in puffing behaviour and in 24-hour cigarette consumption were only slight.The results show clear evidence of both upward and downward self-titration of nicotine and carbon monoxide (and tar) intakes when smokers change to cigarettes with standard yields that differ over the range studied.Introduction Do smokers adjust their nicotine intake to some habitual optimal level when smoking cigarettes of different strengths ? Evidence concerning this self-titration hypothesis is conflicting, but a clear answer is important in planning and evaluating the effects of safer-smoking strategies in which smokers are advised to switch to cigarettes of decreased nicotine, tar, and carbon

Attitudes towards transplantation were investigated in national surveys of the general public (n = 1471), the medical profession (n = 590) and key clinical staff in units referring potential organ donors (n = 380). A clear majority of doctors would like to see more transplants. Only 16 per cent of doctors opposed them on cost grounds, and a 50 per cent 5-year survival rate is seen as more than adequate clinical justification. However, doctors are less supportive of liver and heart grafts than of kidney and cornea grafts. Few lay people would refuse donation of specific organs, but 30 per cent worry that doctors might be pressured into removal of organs when they are not sure the patient is dead. Religious or moral objection is rare. Intensive care unit staff felt the most important factor restricting organ harvest in their own units was dislike of adding to relatives' distress, followed by lack of training in approaching relatives and adverse media publicity. Only 11 per cent thought reservations on brain stem death a likely or possible influence. Enhanced public awareness of the need for transplants was seen as the most important means of increasing organ harvest. Required request would be controversial and perhaps impossible to implement. We conclude that the time, effort and expense involved in potential organ donation do not play a substantial part in limiting referral. Neither do reservations about brain stem death. Increased training of staff (both in communication skills and in the professional responsibility to encourage donation) and greater public awareness are seen as the twin foundations of a realistic approach to enhancing referral.

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The relation between blood carboxyhaemoglobin (COHb) and plasma nicotine concentrations was studied in a group of 12 smokers smoking cigarettes of three levels of standard delivery. While the intake of carbon monoxide from a single cigarette was unrelated to the intake of nicotine, presmoking "trough" concentrations of the two substances (reflecting longer-term exposure) were highly correlated. Various other measures of nicotine exposure were at best only moderately correlated with blood nicotine concentrations.Thus trough COHb concentrations might be used to provide a reliable indication of the exposure to nicotine of individual smokers smoking the same type of cigarette, and of the relative exposure to nicotine of populations smoking cigarettes of different standard deliveries.

SummaryResponse to social cues was studied in two groups of smokers; 14 sedative smokers, who report smoking predominatly under high arousal conditions e.g. anxiety, and 14 stimulant smokers, whose ‘need’ to smoke is greatest under low arousal conditions e.g. boredom. The smoking behaviour of each group was studied in two experimental conditions, during which subjects watched one of two 30 minute video films. The videos were similar apart from the presence of clips of people smoking in one of the films. Seeing people smoke on the video significantly increased smoking rate and intensity in stimulant smokers only. This finding suggests that establishing the precise cues to which different kinds of smokers respond is important in broadening our understanding of the theoretical distinctions made between smokers.

SummaryThe results of 16 published experiments which have investigated the effect of reduced tar and nicotine delivery on cigarette consumption were analysed. Smokers switched to brands of lower delivery were found to have significantly increased consumption, the greatest increases in consumption occurring after the largest reductions in delivery. A linear regression of the data shows the consumption increase predicted for different levels of delivery reduction. The relevance of this data to changes in cigarette consumption taking place in the general smoking population is discussed.

Smoking behaviour and exposure to carbon monoxide, nicotine, and tar were studied in 19 middle-tar smokers. All smoked their own brands for three weeks and then switched to either a conventional low-nicotine, low-tar brand (control) or a medium-nicotine, low-tar cigarette for a further three weeks, the order then being reversed. The medium-nicotine, low-tar brand also had a low delivery of carbon monoxide.With the medium-nicotine, low-tar cigarette mouthlevel delivery and intake of nicotine was similar to that with the smokers' usual brands, and significantly greater than with the control low-tar cigarette. Intake of carbon monoxide from the medium-nicotine, low-tar cigarette was significantly less than with either own or control brands. With both low-tar brands mouth-level exposure to tar was reduced relative to smokers' usual cigarettes. There was no evidence, however, that the reduction in tar exposure was greater with the medium-nicotine University of Cambridge Clinical School, Department of Medicine, Addenbrooke's Hospital, Cambridge CB2 2QQ R STEPNEY, MA, MSC, research psychologist brand than with the control low-tar cigarette. Both lowtar brands were "oversmoked" relative to subjects' usual middle-tar cigarettes.The medium-nicotine, low-tar cigarette was marginally more acceptable than the control brand, and the particular design used in the study resulted in a lower intake of carbon monoxide. Ink terms of reducing mouthlevel exposure to tar, however, the medium-nicotine, low-tar cigarette had no advantage over the control lowtar product. In part this was because the ratio of tar to nicotine delivery obtained by human smokers was not the same as that obtained by smoking machine.

Drugs taken for cancer can interact with each other, with agents taken as part of supportive care, with drugs taken for comorbid conditions (which are particularly common in the elderly patients), and with herbal supplements and complementary medicines. We tend to focus on the narrow therapeutic window of cytotoxics, but the metabolism of tyrosine kinase inhibitors by the cytochrome P450 3A4 enzyme (CYP3A4) makes some TKIs particularly prone to interference with or from other agents sharing this pathway. There is also potential for adverse pharmacokinetic interactions with new hormonal agents used in advanced prostate cancer.