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Biomedical subjects

C Feyerabend

Publications and source records attributed to C Feyerabend.

At least 19 recordsLinked to original sources
PubMed1992

Randomised controlled trial of nasal nicotine spray in smoking cessation.

Studies with nicotine chewing gum and nicotine skin patches indicate that nicotine replacement can help people to give up smoking. The rapidity with which nicotine is absorbed when given as a nasal spray suggests that it might be effective for those for whom the other means of replacement are too slow. The efficacy and safety of a nasal nicotine spray as an adjunct to group treatment for stopping smoking were assessed in a randomised, double-blind, placebo-controlled trial in which 227 cigarette smokers attending the Maudsley Hospital Smokers Clinic received 4 weeks of supportive group treatment plus active nicotine (0.5 mg per shot) or placebo nasal spray. The main end-point was biochemically validated complete abstinence from smoking from the third week of group treatment until the 12-month follow-up. Side-effects were assessed by self-reports and, where necessary, by physical examination. Of subjects assigned to active treatment 26% (n = 30) were validated abstinent throughout the year, compared with 10% (n = 11) of those assigned to placebo (relative abstinence rate 2.6, 95% CI 1.5-4.5, p less than 0.001). The advantage of the active spray was greatest in the heaviest smokers. Plasma nicotine concentrations from the spray were typically between one-half and three-quarters of baseline smoking levels. Tobacco-withdrawal symptoms, craving for cigarettes, and weight gain in abstinent subjects were reduced by the active spray. Minor irritant side-effects were frequent in both active and placebo sprays, but only 2 subjects had the spray discontinued as a result. No serious adverse effects were encountered. Nasal nicotine spray combined with supportive group treatment is an effective aid to smoking cessation.

Administration, Intranasal↗
PubMed1992

Effect of transdermal nicotine patches on cigarette smoking: a double blind crossover study.

The effect of transdermal nicotine patches on ad libitum cigarette smoking was examined in 30 subjects by measuring behavioural, biochemical and subjective aspects of smoking during a week of smoking without patches, and then a week each of nicotine and placebo patches in a randomised double blind crossover design. While wearing nicotine patches the subjects did not reduce the number of cigarettes smoked, but their expired carbon monoxide was reduced by 14%, they obtained less satisfaction from their cigarettes, and reported fewer and weaker urges to smoke. Down-regulation of nicotine intake from cigarettes was imprecise, such that when subjects wore nicotine patches their post-cigarette plasma nicotine concentration increased to an average of 45 ng/ml compared with 37 ng/ml in both no patch and placebo patch conditions. As the nicotine patches produced a plasma nicotine concentration of 15.9 ng/ml in abstinent subjects, this suggests a 22% reduction in nicotine intake from cigarettes while wearing nicotine patches. No serious symptoms of nicotine overdose were reported. It is suggested that the continuous absorption of nicotine from the patch may cause a build-up of acute tolerance to both toxic and pleasant subjective effects from smoking.

Administration, Cutaneous↗
PubMed1992

Nicotine intake and dependence in Swedish snuff takers.

Two studies examining nicotine intake in users of Swedish moist oral snuff are reported. Absorption form a single pinch (2 g) in ten users after overnight abstinence was fairly rapid. The increment in plasma nicotine concentrations averaged 9.9 ng/ml (SD 6.5) after 10 min and peaked at 14.5 ng/ml (SD 4.6) shortly after discarding at 30 min. Among groups of habitual snuff takers (n = 27) and cigarette smokers (n = 35) studied on a day of normal snuffing/smoking, peak blood nicotine levels after use were similar [averaging 36.6 ng/ml (SD 14.4) and 36.7 ng/ml (SD 16.1), respectively], but there was a tendency to higher cotinine levels in the snuffers (399.2 ng/ml versus 306.3 ng/ml). The snuff takers and cigarette smokers reported similar levels of subjective dependence on tobacco. Epidemiological study of Swedish snuff users could clarify whether the cardiovascular risks of tobacco are attributable to nicotine or to other smoke components, as in their case nicotine intake is not accompanied by combustion products.

Adult↗
PubMed1992

Nasal nicotine spray: a rapid nicotine delivery system.

Plasma nicotine concentrations following administration by two types of nasal nicotine spray were compared in ten subjects. Absorption was particularly rapid during the first 2.5 min, the average rise in blood nicotine concentrations during this time being 8.6 ng/ml for the two products, followed by a small further rise to an average peak increase of 10.5 ng/ml 5 min after the dose of 2 mg nicotine base (mean 27.8 micrograms/kg). Despite a four-fold Cmax variation between subjects, the levels of individual subjects were fairly consistent across the two products. There were no significant differences between the two products in blood nicotine concentrations or cardiovascular responses, and the correlation between the AUCs from the two products was 0.68 (P = 0.01). Eight subjects reported subjective feelings of light-headedness or slight dizziness, which are not typical after slower absorption from nicotine gum or skin patches. Blood nicotine levels within the smoking range were soon built up with repeated doses, even in the subject with the least efficient nasal absorption. In a second study of ad libitum use under clinical conditions both products appeared sufficiently acceptable for therapeutic use as an aid to smoking cessation. There was no tendency to escalate to excessive use over 4 weeks, and blood nicotine concentrations in nine subjects averaged only 44% of their prior smoking levels. Only one subject had levels equivalent to prior smoking and possible reasons why this was not more common are discussed.

Administration, Intranasal↗
PubMed1992

Exposure to passive smoking among bar staff.

The median saliva cotinine concentration in 42 non-smoking bar staff in central London and Birmingham was 7.95 ng/ml, indicating a nicotine intake of about 0.6 mg per day. Pubs appear to give rise to exceptionally heavy exposure to environmental tobacco smoke. Passive smoking in pubs is of concern for its impact both on customers and on those for whom the pub is a place of work.

Adult↗
PubMed1992

Determinants of passive smoking in children in Edinburgh, Scotland.

OBJECTIVES: Using saliva cotinine as a quantitative marker, we examined the contribution of factors other than parental smoking to children's passive exposure to tobacco smoke. METHODS: Saliva specimens from a random sample of 734 7-year-old schoolchildren in Edinburgh, Scotland, were analyzed for cotinine. Their parents completed a questionnaire covering smoking habits and conditions in the home. RESULTS: A number of independent predictors of cotinine were identified in addition to the main one of smoking by household members. These predictors included home ownership, social class, day of the week, season of the year, number of parents present, crowding in the home, the number of children in the household, and sex. Cotinine was higher in children from less advantaged backgrounds, during winter, on Mondays, in girls, and when fewer other children were present. The effects were similar between children from nonsmoking and smoking homes. CONCLUSIONS: Questionnaire measures of parental smoking are insufficient to fully characterize young children's exposure to passive smoking. Because socioeconomic variables contribute to measured exposure, passive-smoking studies that treat class as a confounder and control for it may be overcontrolling.

Child↗
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

Quantifying serum antibody class and subclass responses by enzyme immunoassay in humidifier-related disease.

Antibody activity in the major classes and IgG subclasses against antigens in factory humidifier water was quantified by enzyme immunoassay (EIA) in 88 subjects who were exposed at work to the output from these contaminated humidifiers. Those with work-related symptoms had significantly higher mean titres than those who were symptom free, although values overlapped. The individuals with the highest IgG antibody titres also had the highest titres of IgM and IgA antibody, and these parameters did not discriminate between those with and without symptoms any better than the IgG titre. This was also true for the IgG subclasses where activity was predominantly measured in IgG1. Quantifying the IgG antibody allowed us to demonstrate a significant correlation with years of work exposure (P less than 0.001). There was no significant association between antibody and cigarette smoking, as assessed by smoking history and confirmed objectively by serum cotinine levels. There was a significant correlation with total IgG level (P less than 0.001) suggesting that a non-specific immune enhancement may accompany the specific response. The antibody titres were followed up to 3 years after modification of the humidification systems, and during this time symptoms resolved and the antibody levels progressively fell to undetectable levels. The EIA was adapted to measure antigen at nanogram levels thus providing a rapid test for screening of humidifer water as well as a technique that may help identify the nature of the antigens involved.

Air Conditioning↗
PubMed1979

Improved gas chromatographic method and micro-extraction technique for the measurement of nicotine in biological fluids.

A rapid and sensitive method for the measurement of nicotine in plasma, urine, saliva and breast milk is described. An internal standard (quinoline) is added to the samples and these are made alkaline and extracted with diethyl ether. The solvent is evaporated to small bulk and extracted with dilute acid which is then made alkaline. The nicotine is finally extracted into butyl acetate and an aliquot of this extract is injected onto a gas-chromatograph fitted with a nitrogen detector. Quantitation relies on comparison of peak areas and the calibration curve is linear over the concentration range 0.5 to 100 ng ml-1. Nicotine concentrations as low as 0.1 ng ml-1 can be measured. In addition, a micro-method is described which requires only 100 microliter of sample and yields an accurate result in 5 min.

Chromatography, Gas↗
PubMed1978

Adjustment of smokers to dilution of tobacco smoke by ventilated cigarette holders.

This study was designed to examine the extent to which smokers would compensate for the dilution of smoke produced by ventilated cigarette holders. Peak plasma nicotine and carboxyhemoglobin levels were measured in 18 smokers when they had been smoking normally and when they had been using holders which dilute the smoke by about 20% (holder 1) and 60% (holder 2) for periods of 2 days and 7 days. Comparison of the observed blood levels with the "expected" levels estimated from the dilution factors of the holders showed that subjects partially compensated on holder 2 but showed little or no compensation on holder 1. There were no changes in the number of cigarettes smoked when using the holders so any compensation achieved must have been due to increasing the intake from each cigarette. There was wide individual variation in the amount of compensation with about 50% of subjects compensating fairly consistently on both holders. Degree of compensation was not significantly associated with usual cigarette consumption, plasma nicotine and carboxyhemoglobin levels when smoking without a holder, the nicotine yields of the subjects' cigarettes, or the experience of withdrawal symptoms and the degree of satisfaction when using the holders. It cannot be determined from this study whether the compensation observed was mediated by a need to regulate the intake of nicotine rather than some other factor.

Adult↗
PubMed1978

The effect of nicotine on fetal breathing movements in conscious pregnant ewes.

Nicotine (0.14--0.25 mg/kg), injected intravenously or intraarterially into conscious pregnant ewes, caused a decrease in fetal PaO2 within 5 minutes, persisting for up to 30 minutes. There was a significant fall in the incidence of fetal breathing movements. These changes did not occur if the ewe was treated with an alpha-blocking agent (phentolamine) or if the nicotine was infused for 30 minutes at 0.27 to 0.85 mg/minute. Nicotine crossed the placenta; fetal concentrations equaled those in the ewe 5 minutes after the injection and remained at or above maternal levels for 1 hour. Nicotine given directly to the fetus (0.005--0.03 mg/kg estimated fetal weight) stimulated fetal breathing movements in a dose-related manner. We suggest that the maternal injection of nicotine results in a fall of uterine blood flow by a sympathomimetic action, leading to transient fetal hypoxemia and a reduction of fetal breathing movements and that a similar phenomenon may occur when a pregnant woman smokes cigarettes.

Animals↗
PubMed1977

Nicotine chewing gum as a substitute for smoking.

The capacity of nicotine-containing chewing gum to produce plasma nicotine levels comparable to heavy cigarette smoking was tested in 21 subjects. On a fixed schedule of one piece of gum (4 mg nicotine) per hour, the average peak plasma nicotine concentration was 175-7 nmol/l (28-5 ng/ml) compared to 189-3 nmol/l (30-7 ng/ml) obtained from normal ad libitum smoking. Unpleasant side effects were common and in some cases plasma nicotine concentrations were two and even three times as high as with smoking; The chewing gum provided some satisfaction to all but four subjects, but its degree was not related to the concentration of plasma nicotine it produced, neither was there an inverse relation between the plasma nicotine concentration while taking the gum and the subjective sense of missing cigarettesmthis suggests that the capacity of the gum to act as a substitute for smoking is not necessarily related to its capacity to provide nicotine. Flexible dosage dictated by individual needs would probably lower the incidence of side effects and might secure closer approximation to smoking concentrations of plasma nicotine.

Adult↗
PubMed1976

Effect of nicotine chewing gum on smoking behaviour and as an aid to cigarette withdrawal.

In a double-blind, placebo-controlled, crossover trial the effect of 2-mg nicotine chewing gum was studied in 43 smokers when they were smoking as inclined and when they were trying to stop smoking. Although 70% of the smokers stopped smoking during treatment, only 23% were still abstinent after one year. The effect of the nicotine, though significant, was small compared with the overall reduction in smoking. When the subjects were smoking as inclined cigarette consumption was reduced by an average of 37% on the nicotine gum compared with 31% on placebo gum, while avergage carboxyhaemoglobin (COHb) levels were reduced by 26% and 15% on the active and placebo gums respectively. When subjects tried to stop smoking there was a further considerable reduction in cigarette consumption, but no longer any difference between the two gums. Nevertheless, average COHb was still lower on the active gum. Plasma nicotine levels on the nicotine gum averaged only 10-7 ng/ml compared with 27-4 ng/ml after smoking. Better results could be expected with 4-mg nicotine gums.

Adult↗
PubMed1976

Plasma nicotine levels after cigarette smoking and chewing nicotine gum.

Plasma nicotine levels were measured over seven hours of smoking cigarettes (1-2 mg nicotine) in a single subject under standardised conditions, and were compared with the levels obtained from chewing-gum containing either 2 mg or 4 mg nicotine. Levels comparable to those resulting from smoking were not obtained with the 2-mg gum, but peak levels on the 4-mg gum averaged 40-1 ng/ml from the third gum onwards compared with 49-2ng/ml after cigarettes. Nicotine was absorbed much more slowly from the gum than from cigarettes. It took 15-30 minutes for the 4-mg gum to raise the plasma nicotine by an average of 11-9 ng/ml compared with an average increase of 27-8 ng/ml within two minutes of completing each cigarette. In a sample of 15 smokers attending a withdrawal clinic the average plasma nicotine concentration while taking 2-mg nicotine chewing-gum was only 10-8 ng/ml compared with 30-4 ng/ml two minutes after smoking a cigarette. Although plasma nicotine levels equivalent to those following cigarette smoking may be obtained by chewing at least 10 pieces of 4-mg nicotine gum daily, the slower rate of absorption may limit its therapeutic value as a substitute for cigarette smoking.

Absorption↗
PubMed1976

Cigarette smoking and fetal breathing movements.

Cigarette smoking caused a reduction in the incidence of fetal breathing movements in normal and abnormal pregnancies. The size of the reduction varied, being greatest in small-for-dates pregnancies and pregnancies complicated by fetal distress in labour and least in pre-eclamptic pregnancies. The fall in the amount of fetal breathing movements was significantly related to the rise in maternal plasma nicotine after smoking but was unrelated to the rise in barboxyhaemoglobin. Smoking non-nicotine (herbal) cigarettes produced increases in carboxyhaemoglobin concentrations similar to those observed after smoking tobacco cigarettes, and was not associated with a fall in the incidence of fetal breathing movements. Chewing gum containing nicotine produced rises in plasma nicotine concentration similar to those observed after smoking tobacco cigarettes and was associated with a significant reduction in the incidence of fetal breathing movements. Hence nicotine appeared to be the factor in cigarette smoke responsible for the reduction in the incidence of fetal breathing movements. Nicotine was present in the cord blood of infants whose mothers smoked. The possible mechanism by which nicotine caused a reduction in the incidence of fetal breathing movements and its possible relevance to the detrimental effects of smoking on the fetus are considered.

Birth Weight↗