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R Stepney

Publications and source records attributed to R Stepney.

18 recordsLinked to original sources
PubMed1993

Synthesis and platelet aggregation inhibiting activity of acid side-chain modified hydantoin prostaglandin analogues.

A series of hydantoin prostaglandin analogues, in which the hexamethylene moiety of the acid side chain was replaced by other spacing groups possessing either ether, sulphide and/or olefin functionality, were prepared and evaluated for platelet aggregation inhibiting activity. The 4-thia analogue 13*) proved to be the most potent inhibitor (ca. 22x PGE1) and the 3-thia- and 3-oxa-analogues, 6 and 10 respectively, are approximately equipotent with BW245C (ca. 14x PGE1). Z-olefinic analogues (e.g. 11) were usually more potent than their E-isomers (e.g. 12). Structure-activity relationships are discussed in detail.

Alprostadil↗
PubMed1989

Obstacles to organ donation.

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.

Adult↗
PubMed1982

Exposure to carbon monoxide in smokers of middle- and low-tar cigarettes.

The carbon monoxide (CO) exposure of habitual middle-tar (MT) and low-tar (LT) smokers was studied in a group of 78 subjects (38 male and 40 female). CO intake from a single cigarette (measured by the rise in expired-air CO concentration) was significantly less in LT smokers. Longer term exposure, measured by pre-smoking CO levels, was also less in LT smokers, but not significantly so. A CO-based index showed that LT cigarettes were relatively more intensively smoked. Exposure to nicotine and tar was estimated by applying the index of smoking intensity to the standard nicotine and tar yields of the brands smoked. Although an indirect estimate, the results suggest that the intake of tar and nicotine is likely to be appreciably less in LT smokers than in their MT counterparts. The likely difference in intake, however, is not as great as the difference in smoking-machine yields.

Adult↗
PubMed1982

Are smokers' self-reports of inhalation a useful measure of smoke exposure.

The relation between self-assessed and objective measures of inhalation was studied in 75 smokers who assigned themselves to one of four inhalation categories, and also estimated inhalation using a rating scale. The analysis of presmoking carbon monoxide concentration in expired air, and of the rise in carbon monoxide concentration over smoking, provided an objective measure of inhalation. These was a weak but significant correlation between self-rated inhalation and rise in carbon monoxide, but no correlation with the longer-term exposure measured by presmoking levels of carbon monoxide. Differences in exposure to carbon monoxide according to self-assessed inhalation category were non-significant. It is concluded that neither subjective measure of inhalation contributes usefully to the estimation of smoke exposure among smokers who inhale.

Carbon Monoxide↗
PubMed1981

Would a medium-nicotine, low-tar cigarette be less hazardous to health?

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 mouth-level 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 brand than with the control low-tar cigarette. Both low tar 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. In terms of reducing mouth-level exposure to tar, however, the medium-nicotine, low-tar cigarette had no advantage over the control low-tar product. In part this was because of the ratio of tar to nicotine delivery obtained by human smokers was not the same as that obtained by smoking machine.

Adult↗
PubMed1981

Chemotactic response to some arachidonic acid lipoxygenase products in the rabbit eye.

The effects of arachidonic acid, its cyclo-oxygenase and lipoxygenase products and the synthetic chemotactic peptide, formyl-methionyl-leucyl-phenylalanine (FMLP) on leukocyte accumulation in the aqueous humour and intraocular pressure in the rabbit were studied in vivo. Substances were injected into the anterior chamber of the eyes of anaesthetised rabbits using a closed circuit perfusion system. Injection of arachidonic acid, prostaglandins E1 and E2, and the monohydroperoxy and hydroxy acids of the lipoxygenase pathway did not result in any significant accumulation of leukocytes in the anterior chamber. In contrast, FMLP and 5,12-diHETE (Leukotrine B4) resulted in significant dose dependent accumulation of leukocytes into the aqueous humour. Leukocytes appeared in the aqueous humour between 2 and 3 h after the injection of either FMLP or LTB4 and the response was maximal at 4 h. None of the lipoxygenase products tested had any effect on intraocular pressure in contrast to the profound effects observed with arachidonic acid and the E type prostaglandins. FMLP had a small but significant effect on intraocular pressure at the highest dose tested for leukocyte accumulation. These results indicate that the effects of the cyclo-oxygenase products of arachidonate metabolism are mainly vascular in the rabbit eye in contrast to the predominantly cellular effects of lipoxygenase products. Thus in the eye, the interaction of cyclo-oxygenase and lipoxygenase products of arachidonate metabolism may be important in the development of both acute and chronic ocular inflammation.

Animals↗
PubMed1981

Should intake of carbon monoxide be used as a guide to intake of other smoke constituents?

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.

Carbon Monoxide↗
PubMed1979

Self-titration by cigarette smokers.

An 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 low-nicotine cigarettes, which had a standard yield about 50% lower than the medium brands. But 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.

Adult↗