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Biomedical subjects

C Feyerabend

Publications and source records attributed to C Feyerabend.

At least 55 records · Page 3Linked to original sources

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↗

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↗

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↗

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↗

Serum cotinine as an objective marker for smoking habit in head and neck malignancy.

Cigarette-smoking is a well-established aetiological factor in squamous cell carcinoma of the larynx. In Great Britain the majority of patients with laryngeal cancer are treated by radiotherapy with salvage surgery if necessary. A troublesome side effect of radiotherapy is mucositis which may exacerbate hoarseness, dysphagia, airway obstruction or pain. Although it is a common belief that continued smoking and alcohol consumption during radiotherapy may increase the frequency and severity of these side effects this has not been demonstrated objectively. This study confirms and illustrates the relationship between such radiotherapy reactions to continued smoke exposure by using an objective biochemical marker of smoking status.

Alcohol Drinking↗

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↗

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↗

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↗

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↗

The relationship of salivary cotinine to respiratory symptoms, spirometry, and exercise-induced bronchospasm in seven-year-old children.

The effects of passive tobacco smoke exposure upon respiratory symptoms and lung function were assessed in a cross-sectional survey of 770 children 7 yr of age, using cotinine as a quantitative biochemical marker of exposure. Salivary cotinine levels were strongly related to the number of smokers in the home, but three-quarters of children from nonsmoking households had detectable salivary cotinine, and 10% of this group were in the upper two-fifths of the distribution of measured tobacco smoke exposure. Smoking by persons other than members of the household may deserve greater attention in future studies of young children. After adjustment for housing tenure, most respiratory symptoms were unrelated to salivary cotinine, but a "tendency for colds to go to the chest" was twice as prevalent in the upper two-fifths as in the lower two-fifths of the cotinine distribution. No association was found between salivary cotinine and reports of wheeze or measured reduction in FEV1 after 6 min of free running. After adjustment for sex, height, test conditions, and housing tenure, all baseline spirometric indices except FVC were inversely associated with salivary cotinine. Only FEF75-85 and FEF75 were significantly reduced, the difference for each index between the top and bottom quintiles of the cotinine distribution being about 7%, equivalent to a reduction of 1.1% (95% CL, 0.1 to 2.1%) per doubling of cotinine concentration. These changes may be evidence of small airways damage, which could later progress to more severe respiratory impairment.

Asthma↗

Passive smoking, salivary cotinine concentrations, and middle ear effusion in 7 year old children.

OBJECTIVE: To assess the contribution of passive exposure to tobacco smoke to the development of middle ear underpressure and effusion. DESIGN: Cross sectional observational study. SETTING: One third of the primary schools in Edinburgh. SUBJECTS: 892 Children aged 6 1/2 to 7 1/2 were examined, and satisfactory tympanograms were obtained in 872. Results of assay of salivary cotinine concentrations were available for 770 children, and satisfactory tympanograms were available for 736 of these. END POINT: Correlation of the prevalence of middle ear underpressure and effusion with concentrations of the marker of nicotine, cotinine, in the saliva of the children. MEASUREMENTS AND MAIN RESULTS: Middle ear pressure and compliance were measured in both ears by impedance tympanometry. Salivary cotinine concentrations were assayed by gas-liquid chromatography. Cotinine concentrations increased with the number of smokers in the household. Girls had higher concentrations than boys, and children living in rented housing had higher concentrations than those living in housing owned by their parents. There was a trend towards more abnormal tympanometric findings with increasing cotinine concentration, the odds ratio for a doubling of the cotinine concentration being 1.14 (95% confidence interval 1.03 to 1.27). After adjustment for the sex of the child and housing tenure the odds ratio for a doubling of the cotinine concentration was 1.13 (1.00 to 1.28). CONCLUSIONS: The results of this study are consistent with those of case-control studies of children attending for an operation to relieve middle ear effusion. They indicate that the disease should be added to the list of recognised hazards associated with passive smoking. About one third of the cases of middle ear effusion in this study were statistically attributable to exposure to tobacco smoke.

Acoustic Impedance Tests↗

Effect of smoke-free cigarettes on 24 h cigarette withdrawal: a double-blind placebo-controlled study.

In a double-blind randomised trial, 40 cigarette smokers used either nicotine-containing or placebo smoke-free cigarettes during 24 h abstinence from smoking. Subjects in the nicotine group experienced smaller increases in irritability and difficulty concentrating and fewer urges to smoke than those who received placebo. Nicotine smoke-free cigarettes were rated as more satisfying, more helpful and more effective in relieving craving than placebo. After 24 h use nicotine smoke-free cigarettes provided average blood nicotine levels of 6.3 ng/ml, i.e., 29.2% of smoking levels. The most frequent side effects were irritation of the throat and coughing. Overall, side effects were rated as not serious. Although the smoke-free cigarette in its present form is not very efficient in delivering nicotine, it was effective in alleviating initial tobacco withdrawal. It is possible that by providing both nicotine and "behavioural" replacement it may be particularly useful in the first stages of stopping smoking. The product is worth further investigation.

Adult↗

Elimination of cotinine from body fluids: implications for noninvasive measurement of tobacco smoke exposure.

Cotinine elimination from plasma, saliva, and urine was studied over 11 days in five subjects (three nonsmokers and two occasional smokers). Half-lives for cotinine averaged 16-19 hours in the different body fluids (range 10 to 27 hours between subjects). There was no tendency for the half-life in saliva to be longer than in plasma or urine. We conclude that choice of body fluid for cotinine assay in smoking studies should depend on practical rather than pharmacokinetic considerations.

Adult↗

Nicotine replacement in smoking cessation. Absorption of nicotine vapor from smoke-free cigarettes.

Nicotine replacement is a promising new approach to aid smoking cessation, and various methods of delivery are being developed. One new device is a smoke-free cigarette (Favor) that has been test-marketed in several US states. Without lighting up, it delivers nicotine vapor and is free of other harmful products of tobacco smoke. To examine its therapeutic potential, we measured plasma nicotine concentrations before, during, and after its use in eight male subjects. Very little nicotine was absorbed when it was puffed like a conventional cigarette. However, with an intensive schedule of puffing at four further smoke-free cigarettes over a 20-minute period, plasma nicotine concentrations were increased by an average of 17.3 ng/mL (107.3 nmol/L) (range, 10.9 to 30.4 ng/mL [67.6 to 188.5 nmol/L]). Heart rate and blood pressure also increased significantly. The rate of nicotine absorption was slow and resembled that obtained from nicotine chewing gum, suggesting that most of the nicotine was deposited in the mouth, throat, and large airways and did not reach the lung alveoli. Despite the slow absorption, the plasma nicotine levels produced could be of therapeutic value as an aid to smoking cessation.

Absorption↗

Comparison of tests used to distinguish smokers from nonsmokers.

Questionnaire and biochemical measures of smoking were studied in 211 hospital outpatients. Eleven different tests of smoke intake were compared for their ability to categorize smokers and nonsmokers correctly. The concentration of cotinine, whether measured in plasma, saliva, or urine, was the best indicator of smoking, with sensitivity of 96-97 per cent and specificity of 99-100 per cent. Thiocyanate provided the poorest discrimination. Carbon monoxide measured as blood carboxyhaemoglobin or in expired air gave sensitivity and specificity of about 90 per cent. Sensitivities of the tests were little affected by the presence among the claimed nonsmokers of a group of 21 "deceivers" who concealed their smoking. It is concluded that cotinine is the measure of choice, but for most clinical applications carbon monoxide provides an acceptable degree of discrimination and is considerably cheaper and simpler to apply.

Carbon Monoxide↗