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Biomedical subjects

M A Russell

Publications and source records attributed to M A Russell.

At least 73 records · Page 4Linked to original sources
PubMed1991

Sensitivity and tolerance to nicotine in smokers and nonsmokers.

We studied the responses of smokers and lifelong non-smokers to transdermal nicotine patches over 24 h in three groups of subjects: non-smokers on a 15 mg patch (n = 8), non-smokers on a 30 mg patch (n = 8) and smokers on a 30 mg patch (n = 8). Unexpectedly, the non-smokers appeared to absorb nicotine more rapidly. The increase in blood nicotine concentrations of non-smokers over the first 2 h of patch use was double that of the smokers, with mean increases of 4.5 (SD = 3.7), 10.9 (SD = 4.2) and 4.1 (SD = 2.7) ng/ml in the three groups, respectively (P less than 0.005). The smokers had no pleasant or unpleasant effects from the 30 mg patch (X Cmax 13.9 ng/ml, SD = 4.9; Tmax 8.75 h) but all eight non-smokers experienced mild nausea and lightheadedness (P less than 0.01) within the first hour, and seven dropped out (P less than 0.01) at 3-8 h due mainly to severe nausea, vomiting or headache (X Cmax 18.4 ng/ml, SD = 4.9; Tmax 5.25 h). Only one non-smoker dropped out on the 15 mg patch, but five had transient nausea in the first hour (X Cmax 7.9 ng/ml, SD = 3.0; Tmax 8.0). Our study provides evidence of chronic pharmacodynamic nicotine tolerance in smokers, but does not address whether this is acquired or innate. The higher rate of transdermal nicotine absorption in non-smokers is unexplained and requires replication.

Administration, Cutaneous↗
PubMed1991

Factors determining exposure to passive smoking in young adults living at home: quantitative analysis using saliva cotinine concentrations.

Saliva cotinine concentrations were used to examine determinants of exposure to environmental tobacco smoke in 393 non-smoking students (age range 16-19 years) attending a sixth form college and living at home. Average concentrations were low (median 0.60 ng/ml), reflecting partly the warm weather at the time of the survey and partly the predominantly middle class sample. Despite this, cotinine levels were strongly related to the extent of self-reported passive smoking in the past three days (medians 0.30, 0.60, 0.90 and 1.35 ng/ml in those reporting 'None at all', 'A little', 'Some' and 'A lot' respectively, p less than 0.0001). Individual sources of environmental tobacco smoke identified were smoking by mothers (p less than 0.0001), by fathers (p less than 0.01), and exposure at college (p less than 0.001) and when out in the evenings (p less than 0.001). The results indicate that exposure outside the home may become of equal or greater importance than family smoking in determining the overall passive smoking dose received by this age group.

Adolescent↗
PubMed1991

The future of nicotine replacement.

Following in the wake of progress forged by nicotine chewing gum, a new generation of nicotine replacement products will soon be available as aids to giving up smoking. These range from nicotine skin patches, which take 6-8 hrs to give very flat steady-state peak blood levels, to nicotine vapour inhalers which mimic the transient high-nicotine boli that follow within a few seconds of each inhaled puff of cigarette smoke. Other products undergoing clinical trials include a nasal nicotine spray and nicotine lozenges. It is argued here that it is not so much the efficacy of new nicotine delivery systems as temporary aids to cessation, but their potential as long-term alternatives to tobacco that makes the virtual elimination of tobacco a realistic future target. Their relative safety compared with tobacco is discussed. A case is advanced for selected nicotine replacement products to be made as palatable and acceptable as possible and actively promoted on the open market to enable them to compete with tobacco products. They will also need health authority endorsement, tax advantages and support from the anti-smoking movement if tobacco use is to be gradually phased out altogether.

Administration, Cutaneous↗
PubMed1990

Non-smokers show acute tolerance to subcutaneous nicotine.

Plasma nicotine concentrations following subcutaneous (SC) injection were measured in six subjects who included three life-long nonsmokers. On average, a peak plasma level of 8.5 ng/ml (SD = 3.1) was reached 15 min after the mean dose of 13.25 micrograms/kg nicotine base. Subjective effects were reported by five subjects. The peak heart rate response (mean boost 11 beats per min at 10 min) preceded and was already declining by the time plasma nicotine concentrations peaked. Hysteresis plots showed clear evidence of acute nicotine tolerance in subjects who had never smoked, indicating that acute tolerance is not an acquired phenomenon. The acquisition by smokers of chronic tolerance to nicotine has not yet been systematically demonstrated. Reliable dose-response studies in smokers and nonsmokers are needed, and use of the SC route for this purpose is discussed.

Adult↗
PubMed1990

Clonal analysis of segmental and compartmental homoeotic transformations in polycomb mutants of Drosophila melanogaster.

We describe two new effects of Polycomb mutations on the determination of compartments in the wing of Drosophila. Ventral and posterior wing compartments are transformed partially to their dorsal and anterior counterparts. Although these new phenotypes are most strongly expressed in lethal pharate adults heteroallelic for Pc2 and a new allele PcT2, they are also found regularly but with low expressivity as dominant phenotypes of all the other Pc alleles we tested. Several different intersegmental homoeotic transformations caused by Polycomb have previously been described, leading to the hypothesis that Polycomb regulates the activity of certain selector genes normally active in specific segments. We now show that the degree of expression of the inter- and intrasegmental transformations are highly correlated in a range of different Pc genotypes, and that more than one determinative decision can be affected in a single compartment. This suggests that the wild-type Pc product may act as a general regulator of several different selector genes so as to influence both early embryonic and later determinative decisions in the imaginal discs. To test this idea we used clonal analysis to look at the effects of Pc on clonal restrictions at the dorsoventral and anterioposterior compartment boundaries, and its time of action with respect to each phenotype.

Alleles↗
PubMed1990

Genetic and molecular analysis of vgU and vgW: two dominant vg alleles associated with gene fusions in Drosophila.

In the absence of a vg+ gene, extensive cell death occurs in third instar imaginal discs, which results in a complete loss of adult wing margin structures. Essentially all molecularly characterized vg alleles are associated with deletions or insertions of DNA into the vg locus. These alterations reduce or eliminate a 3.8-kb vg-specific transcript, resulting in recessive loss of function alleles. We report here the analysis of two dominant vg alleles which have been identified (vgU and vgW). The vgU allele is associated with a chromosomal inversion which splits the vg locus, resulting in a gene fusion between vg and the mastermind (mam) neurogenic locus. Reversion analysis of vgU indicates that sequences from the mam locus are required for vgU dominance. The vgW allele is also the result of a chromosomal inversion, in this case resulting in a gene fusion between vg and the homeobox-containing invected (inv) gene. It is also associated with novel dominant homeotic transformations. Revertant analysis indicates that sequences from inv are required for the dominant wing and dominant homeotic effects of vgW. The vg dominance does not appear to be mediated through a reduction of vg expression or a novel fusion transcript in either vgU or vgW. The results are consistent with a model in which inappropriate expression of inv causes the dominant homeotic effects seen in vgW.

Alleles↗
PubMed1990

The nicotine addiction trap: a 40-year sentence for four cigarettes.

It is generally recognized that smoking causes more preventable illness than any other form of drug addiction. Despite this, and unlike the case with other addictions, few services are provided to help people to give it up. Yet nicotine is highly addictive. Its role in the recruitment process, the development of dependence and as a block to smoking cessation are discussed within the context of the typical smoking career. Over 90% of teenagers who smoke 3-4 cigarettes are trapped into a career of regular smoking which typically lasts for some 30-40 years. Only 35% of regular smokers succeed in stopping permanently before the age of 60, although the large majority want to stop and try to stop. The pharmacological effects of nicotine and other factors that determine dependence on smoking, together with the attitudinal and cognitive factors that determine motivation to stop smoking, are considered within the framework of a decision-making model which reflects the cycles of change in smoking status at different stages of the smoking career. It is argued that, in future intervention strategies, the newly developed treatment approaches should be included to complement traditional motivational approaches based on educational and restrictive measures.

Adolescent↗
PubMed1990

A rapid gas-liquid chromatographic method for the determination of cotinine and nicotine in biological fluids.

A rapid method is described for the simultaneous measurement of nicotine and cotinine in biological fluids using capillary column gas-liquid chromatography. Using 100 microliters sample volume the lower limit of detection for both nicotine and cotinine was 100 pg mL-1, allowing the method to be used for the measurement of these compounds in both smokers and non-smokers. The extraction time is 3 min per sample, and by using multi-pipetting and vortexing systems 250 samples can be extracted per day. The average coefficient of variation over the nicotine range 1.0 to 100 ng mL-1 was 3.9% and for cotinine over the range 1.0 to 1000 ng mL-1 was 2.2%. Saliva cotinine concentrations were quantitatively related to passive exposure to parental smoking in a population study of 1118 non-smoking schoolchildren.

Chromatography, Gas↗
PubMed1990

Effect of ulcerative colitis and smoking on rectal blood flow.

Rectal blood flow was measured by laser doppler flowmetry over 60 minutes in eight patients with colitis in remission and eight healthy male non-smokers. Ten smokers were also examined on two occasions, one of which included smoking a cigarette. Plasma nicotine concentrations were measured in smokers. All subjects showed a pronounced fall in rectal blood flow in the first 30 minutes and patients with colitis had significantly higher values compared with smokers (p less than 0.002; p less than 0.04) and non-smokers (p less than 0.007; p less than 0.002) during the first and second 30 minutes respectively. Values in smokers and non-smokers were similar, but smoking a cigarette was associated with a significant fall in blood flow (p less than 0.04) and this change was inversely related to the rise in plasma nicotine concentration (r = -0.63; p less than 0.05). The findings may be relevant to the association between colitis and the smoking history.

Adult↗
PubMed1989

A new class of orally active glycol renin inhibitors containing phenyllactic acid at P3.

We prepared a new series of renin inhibitors based on dipeptide glycols, replacing the P4-P3 subsites with an O-(N-morpholinocarbonyl)-3-L-phenyllactic acid residue. This modification proved bioisosteric with Boc-L-phenylalanine, giving rise to highly potent human renin inhibitors (1-5 nM), e.g., SC-46944 (IC50 = 5 nM). Moreover, this change produced compounds that are orally efficacious in reducing plasma renin activity in salt-depleted marmosets.

Animals↗
PubMed1989

Nicotine gum use and outcome in a general practitioner intervention against smoking.

In a general practitioner intervention against smoking (employing nicotine chewing gum) smokers who used more than a box of gum were, prior to the intervention, more motivated to quit smoking and more dependent than those who did not use more than a box. They were also older. Even after controlling for demographic, dependence, motivational and previous success factors, those who used more than a box of gum had a significantly enhanced probability of success compared with other smokers. Although causal conclusions cannot be drawn from these analyses, stress on the importance of persistence in use of the gum is recommended.

Adult↗
PubMed1989

Subjective and behavioural effects of nicotine in humans: some sources of individual variation.

Despite its addictiveness, the subjective effects of nicotine in "smoking doses" are of low intensity compared with those of other addictive drugs. Although mildly pleasurable to many regular users, it causes no striking euphoriant effects and its effects on mood, performance and the level of arousal are relatively small. This chapter does not attempt to list or review the numerous effects of nicotine, but focuses instead on some of the multiple sources of individual variation. The subjective and behavioral effects of nicotine in humans differ markedly, not only between individuals but also within individuals, according to the stage of their smoking career, their level of dependence and the time since their last few doses. Some of the influences and mechanisms discussed include innate and acquired factors, pharmacokinetic factors, acute and chronic tolerance, learning and conditioning. It is not clear to what extent the effects of nicotine are primary, or how much they reflect reversal or relief of acquired withdrawal effects. Only one study has found a "rebound" element in the effects of withdrawal and although chronic exposure to nicotine induces an increase in the number of nicotinic receptors, chronic tolerance to nicotine has not been demonstrated in humans. Acute tolerance (tachyphylaxis) develops rapidly to many of the effects of nicotine and is completely reversible after nicotine depletion. Other effects of nicotine are less sensitive to acute tolerance. It is suggested that it is the effects of nicotine at postsynaptic receptors that are most susceptible to acute tolerance and that those mediated by its action at presynaptic receptors are less sensitive to it. Due to accumulation of nicotine and other pharmacokinetic factors, for most of the day and much of the night, regular smokers have high levels of acute tolerance to nicotine. In other words, there is a chronic partial blockade of its agonist effects at postsynaptic receptors. This explains why nicotinic receptors are upregulated rather than downregulated and why heavy smokers experience no subjective effects from a cigarette smoked during the course of a normal smoking day. When the effects of acute tolerance are unmasked after abstinence for 24 h, it is the more addicted heavy smokers who experienced more severe withdrawal effects who also have stronger subjective and heart rate effects following the first post-abstinence cigarette. Their greater sensitivity to nicotine after abstinence may reflect their higher density of unoccupied nicotinic receptors. On the other hand, those who have higher innate sensitivity may be more likely to take up smoking and to become more dependent if they

Behavior↗
PubMed1989

Prospective study of factors predicting uptake of smoking in adolescents.

Risk factors for the uptake of cigarette smoking were examined prospectively in 2159 non-smoking secondary schoolchildren aged 11-13 who participated in a survey in 1983 and were followed up 30 months later, by which time 35 per cent had taken up smoking. In a multivariate logistic model, the strongest predictors to emerge were prior experimentation with cigarettes and sex, with more girls (41%) than boys (30%) starting to smoke. Other predictors of taking up smoking were being uncertain about smoking in the future, reporting having been drunk, having a boy or girl friend, believing teachers and friends would not mind if they took up smoking, and giving lower estimates of prevalence of smoking among teachers. Parental smoking behaviour and attitudes, beliefs about the effects of smoking on health, opinions about smoking and perceived strictness of parents did not predict take up of smoking when other variables were controlled for. The odds of taking up smoking varied from 0.24 (risk = 0.19) for a child with the most favourable combination of risk factors to 3.49 (risk = 0.78) for a child with the worst prognosis. These results differ from those of many cross sectional studies and hence indicate the importance of a prospective approach to this type of research.

Adolescent↗
PubMed1988

Loss of acute nicotine tolerance and severity of cigarette withdrawal.

Twenty-one smokers underwent 24-h abstinence from cigarettes. Both prior to, and after, the abstinence period cardiovascular and subjective effects of smoking a cigarette were measured. Withdrawal symptoms found during abstinence were: irritability, depression, hunger, difficulty concentrating, restlessness and urges to smoke. In addition, the subjects reported feeling physically less well. Withdrawal discomfort was positively correlated with the strength of the subjective effects (e.g. dizziness, nausea) of smoking the post-abstinence cigarette after taking account of estimated nicotine boost from that cigarette. A similar, though only marginally significant association was found between withdrawal severity and heart rate boost from the post-abstinence cigarette. Our results suggest that the severity of withdrawal may be related to loss of acute tolerance to nicotine. It is not clear whether this is due to more rapid nicotine clearance, constitutional differences in sensitivity to nicotine in the absence of acute tolerance, or other factors. There was no evidence to support the view that higher chronic tolerance to nicotine's heart-rate effects was associated with more severe withdrawal. If anything, the reverse appeared to be the case.

Adult↗
PubMed1988

District programme to reduce smoking: can sustained intervention by general practitioners affect prevalence?

A total of 101 general practitioners in 27 practices in inner London took part in a quasi-experimental study designed to examine whether a brief intervention applied to all smokers seen by general practitioners and sustained on a continuous basis could in time have a cumulative effect and reduce the prevalence of smoking among their patients. Of 21 practices approached in our local district (Camberwell), seven were willing to undertake brief intervention with support from the smokers' clinic (SBI), four opted for intervention without support (BI), and six acted as usual care controls. A further 10 out of 12 practices approached in South Hammersmith provided an unselected group of usual care controls. A series of six cross-sectional surveys were conducted over a three-year period. Each survey consisted of all adult patients attending to see a doctor during a defined two-week period, sample sizes averaging just over 9000 per survey. The estimated decline in self-reported smoking prevalence over the 30-month period following the start of intervention was 5.5% (from 36.4% to 30.9%) in the SBI group compared with 2.1% for BI and 2.8% and 3.0% in the two usual care control groups, the decline in the SBI group being significantly greater than in the other groups which did not differ significantly between each other. These interim results provide encouraging evidence that brief intervention by general practitioners with support and back-up from a local smokers' clinic can, when sustained on a continuous basis, reach sufficient smokers to reduce smoking prevalence in their practice populations. However, firm conclusions must await longer periods of observation now that the other Camberwell practices have adopted the SBI procedures.

Age Factors↗