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Biomedical subjects

C Feyerabend

Publications and source records attributed to C Feyerabend.

At least 91 records · Page 5Linked to original sources

Relation of nicotine yield of cigarettes to blood nicotine concentrations in smokers.

Blood nicotine and carboxyhaemoglobin (COHb) concentrations were studied in 330 smokers (206 women and 124 men). Blood nicotine concentrations in individual smokers varied from 25 to 444 nmol/l (4 to 72 ng/ml). The average concentration, 203 nmol/l (33 ng/ml), was the same in the men and the women, although cigarette consumption was higher in the men. Despite large differences in nicotine yield, there was no relation between blood nicotine concentration and the type of cigarette smoked: smokers of plain, untipped cigarettes (1.9 mg nicotine), cigarettes with unventilated filters (1.3 mg nicotine), and cigarettes with ventilated filters (0.8 mg nicotine) had similar blood nicotine concentrations. Cigarette consumption was also similar in these three groups. The correlation between blood nicotine concentration and nicotine yield of cigarette, though significant, was low (0.21, p < 0.001), showing that the nicotine yield of the cigarettes accounted for only 4.4% of the variation in blood nicotine concentrations. Similarly, the low correlation of 0.30 between COHb concentration and cigarette consumption suggests that cigarette consumption accounted for only 9% of the variation in the amount of smoke taken into the smokers' lungs. These results suggest that the assumed health advantage of switching to lower-tar and lower-nicotine cigarettes may be largely offset by the tendency of smokers to compensate by increasing inhalation. The findings of epidemiological studies showing lower risks with filter-tipped cigarettes may be attributable to other factors such as biases in the samples and changes in the quality and carcinogenicity of tobacco tar, rather than to reduced tar intake.

Carboxyhemoglobin↗

A new age for snuff?

Blood-nicotine levels were measured during non-inhaled cigar smoking and after taking snuff. The rate of nicotine absorption from non-inhaled cigar smoking was slow. This may explain why many cigarette smokers continue to inhale when they switch to cigars. In contrast, the rate of absorption from snuff was extremely rapid. Peak levels which matched those of cigarette smoking were reached within 5 min. Snuff could be an acceptable and less harmful substitute for cigarette smoking.

Humans↗

Smokers' response to shortened cigarettes: dose reduction without dilution of tobacco smoke.

This study was designed to examine the response of smokers to shortening their usual brand of cigarettes. The shortening reduces the dose of smoke available from each cigarette without affecting concentration and therefore differs from dose reduction by dilution, which occurs when smokers switch to cigarettes with lower tar and nicotine deliveries. Measures of smoking behavior (e.g., cigarette consumption, puff rate), mouth-level nicotine intake (calculated from butt content), and intake to the lungs (plasma nicotine and COHb) were made in 10 smokers after 48 hr ad libitum smoking of full, three-quarter, and half-length cigarettes in a Latin square design. Mouth-level smoke intake was maintained on shortened cigarettes due to a combination of 2 types of compensatory maneuver: (1) by increasing the intensity of puffing and thereby extracting proportionately more of the smoke available from each cigarette and (2) by smoking more cigarettes. The amount of smoke inhaled, on the other hand, was only partially maintained (58% compensation). This was achieved by increase in cigarette consumption alone. There was achieved by increase in cigarette consumption alone. There was no evidence of any compensatory increase in the amount of smoke inhaled from each cigarette. Increase in consumption was thus the only maneuver that contributed to maintaining smoke intake at lung level; mouth-level intake was regulated by increasing intake per cigarette as well as consumption.

Adult↗

Assay of nicotine in biological materials: sources of contamination and their elimination.

A previous method for the measurement of nicotine in biological samples was subject to occasional interference from a contaminant which eluted simultaneously with the internal standard (quinoline). This has been rectified by substituting isoquinoline as the internal standard and modifying the operating conditions of gas chromatography. Other source of contamination in nicotine assays such as the analytical reagents, the atmosphere and the sample itself are discussed in detail.

Chromatography, Gas↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Plasma nicotine levels after smoking cigarettes with high, medium, and low nicotine yields.

Plasma nicotine three minutes after smoking a cigarette was measured in 10 sedentary workers in mid-morning and five hours later on four typical working days. The average mid-morning level after they had been smoking their usual cigarettes (mean nicotine yield 1-34 ng) was 150-4 nmol/l (24-4 ng/ml) (range 95-6-236-7 nmol/l (15-5-38-4 ng/ml)). Despite great variation between smokersthe mid-morning levels of each smoker were fairly consistent over the four mornings and correlated 0-82 with their carboxyhaemoglobin levels. After continuing to smoke their usual brand or switching to a high-nicotine brand (3-2 mg) average afternoon levels of 185-6 and 180-0 nmol/6 (30-1 and 29-2 ng/ml) respectively were not significantly higher than the morning levels, but after switching to low-nicotine cigarettes (0-14 mg) the plasma nicotine dropped to an average of 52-4 nmol/l (8-5 ng/ml). The changes between morning and afternoon while smoking usual or high-nicotine cigarettes showed marked individual variation. The findings suggest that the plasma nicotine level just after a cigarette depends more on the way the cigarette is smoked than on its nicotine yield or the number which have been smoked over the preceding few hours.

Adult↗

Blood and Urinary nicotine in non-smokers.

Of 39 urban non-smokers about half had measurable quantities of nicotine in their plasma (range 0 to 5times5 ng. per ml.) and almost all had nicotine in their urine during the early afternoon. The average concentration of urinary nicotine in non-smokers under natural conditions was 10times7 ng. per ml., but after deliberate exposure to tobacco smoke (mean duration seventy-eight minutes) in an unventilated room (38 p.p.m. of carbon monoxide) the average urinary nicotine level (80 ng. per ml.) was significantly higher than in non-smokers who had not been deliberately exposed to smoke (P less than 0times 001). Under natural conditions there was no overlap between the urine levels of non-smokers and the far higher levels of 18 smokers (mean 1236 ng. per ml.), suggesting that urinary nicotine may provide a more accurate assessment of an individual's smoking-status than blood-carboxyhaemoglobin. It is concluded that, as a result of passive smoking, most urban non-smokers have measurable amounts of nicotine in their bodyfluids for most of their lives.

Air Pollution↗

A rapid gas-liquid chromatographic estimation of nicotine in biological fluids.

A rapid gas-liquid chromatographic method for the estimation of nicotine in plasma is described. Nicotine is extracted from alkalinized plasma into diethyl ether. This is then concentrated by evaporation and, after an acid back extraction is re-extracted into n-heptane (nitrogen detector) or dichloromethane (flame ionization detector) before injection onto the gas chromatography. Thirty samples a day can be analysed by this method which enables concentrations of 0.1 ng ml- minus 1 nicotine to be measured. It is thus possible to measure nicotine in plasma and urine samples from non-smokers.

Chromatography, Gas↗