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Biomedical subjects

N J Haley

Publications and source records attributed to N J Haley.

At least 55 records · Page 3Linked to original sources

Thyroid hormone levels and cigarette smoking in baboons.

Using a primate animal model, two studies were undertaken to examine the effects of cigarette smoking on thyroid hormone levels. In study 1, mean total triiodothyronine (total T3) and mean total thyroxine (total T4) levels were measured in two groups of baboons (Papio cynocephalus) who were taught to smoke cigarettes using operant conditioning techniques. The smokers were divided into established and naive smokers according to pack-years of exposure. A control group of never-smoker baboons was included for comparison. Blood sampling was done after long-term cigarette consumption and again 1 week after cigarette deprivation. In the naive smoker group, mean total T3 concentrations were reduced below control group values (P less than 0.05). After cigarette deprivation for 1 week, mean total T3 values returned to normal. No significant differences in total T4 levels were observed in either group. In study 2, we assessed some other indices of thyroid function. The same groups of baboons were divided into good and poor smokers by plasma cotinine and blood carboxyhemoglobin (% COHb) levels during 28 weeks of cigarette smoking activity. Immediate fluctuations and reductions in total T3 levels were observed that were not accompanied by reductions in total T4. The animals were then cigarette deprived for 1 week and blood samples were obtained every other day during this period. Significant increases in total T3 concentrations were observed in poor smokers immediately after cessation. Both groups also exhibited significant reductions (P less than 0.05) in T3 uptake and free T4 index (FT4I) when compared to control group values. These data suggest that poor smokers are more susceptible to thyroid hormone level shifts than more established smokers, since the established smokers become habituated to the compounds contained in cigarette smoke through repeated exposure.

Animals↗

Biochemical epidemiology of cervical neoplasia: measuring cigarette smoke constituents in the cervix.

In preparation for an epidemiological investigation of cigarette smoking and cervical neoplasia, we studied methods of measuring cervical exposure to tobacco smoke. The measurement of cotinine in cervical flushes by radioimmunoassay proved to be highly accurate in distinguishing smokers from nonsmokers, achieving 100% sensitivity and 97% specificity. In most subjects, quantitative levels of cervical cotinine and nicotine mirrored recent smoking intensity. Some of the apparent exceptions may have resulted from metabolic/secretory traits of the subjects. If so, the biochemical measurement of smoke constituents in the cervix might prove more valuable for epidemiological studies of cervical neoplasia than data on current smoking behavior collected by interview.

Adolescent↗

Nicotine administration to rats: methodological considerations.

The effects of nicotine on normal physiological function are of increasing concern. Preliminary to studies on the effects of prenatal exposure to nicotine, we examined methods of administering nicotine to rats. Drinking water containing nicotine was not palatable to rats and was an unsatisfactory method in our hands, producing weight loss and large decreases in fluid intake. Administration of nicotine in a complete liquid diet produced better results but the data suggest that oral administration of nicotine may interfere with absorption of some nutrients. Osmotic mini-pumps were found to be the best mechanism of nicotine delivery of those tried. There were no significant effects on food or water intake nor on weight gain, particularly when using a short term anesthetic for pump implantation. Plasma nicotine and cotinine levels were directly correlated to dose of nicotine delivered. Plasma nicotine levels similar to levels reported in humans were obtained.

Administration, Oral↗

Uptake of sidestream smoke by Syrian golden hamsters.

An inhalation bioassay with Syrian golden hamsters is being conducted to evaluate the toxic and carcinogenic potential of cigarette sidestream smoke (SS) relative to mainstream smoke (MS). A Hamburg II smoking machine is used to deliver MS by nose-only exposure to hamsters and a modification allows for the simultaneous collection of SS for whole-body delivery to a different rack of animals. The tolerated dose of SS was determined by varying the air/smoke dilutions drawn through the animal restrainers. Preliminary data indicated that 20% carboxyhemoglobin (COHb) could be obtained in SS-exposed animals without fatality. Optimum exposure levels were determined. Monthly measurements of COHb, nicotine and cotinine indicate that the SS-exposed animals are absorbing slightly higher amounts of these smoke constituents than the MS-exposed hamsters. Tumor incidence and carcinogenicity data are being collected through complete necropsy and histology protocols and uptake data continue to be collected. These studies should help elucidate the carcinogenic potential of SS which has been suggested from its composition and from recent epidemiological data of cancer incidence in non-smokers.

Animals↗

Population screening for cholesterol determination. A pilot study.

A screening for plasma cholesterol levels was conducted at six sites in the New York metropolitan area and involved hospitals, health professionals, paraprofessionals, media experts, and instruments that provided cholesterol levels rapidly. During the five days of the testing, over 12,000 participants were screened. Because the program was limited to customary working hours and because of self-selection of participants, the subjects were probably an unusually health-conscious group as evidenced by the low prevalence of cigarette smokers (11%). Nevertheless, 12% were at moderate risk and 16% were at high risk for coronary heart disease. Approximately half of the population reported never having had their cholesterol levels tested, and over 40% had no idea what levels were optimal. A subsample of patients at risk was screened by telephone survey. In the majority of cases, when a patient's physician was consulted for advice, no action was recommended. Our results demonstrate that a large population screening can be implemented, that at least certain segments of the public will respond to such a program, and that educational efforts must be directed at both the public at large and physicians.

Adult↗

Short-term studies on the in vivo metabolism of N-oxides of nicotine in rats.

This study was designed to examine the in vivo reduction of the N-oxidation products of nicotine metabolism in rats. Male Fischer-344 rats were divided into one control and three experimental groups (n = 20). Each treatment group received either 0.02% trans-nicotine N'-oxide, 0.02% cis-nicotine N'-oxide, or 0.02% nicotine N,N'-dioxide in drinking water for 3 wk. After 7 d of metabolite administration, plasma nicotine levels in the trans-nicotine N'-oxide group rose to twice that of the cis-nicotine N'-oxide or nicotine N,N'-dioxide group. Plasma cotinine [1-methyl-5-(3-pyridinyl)-2-pyrrolidinone] concentrations reached maximum levels during wk 1 in the cis-nicotine N'-oxide and nicotine N,N'-dioxide groups but continued to increase for another 7 d in the trans-nicotine N'-oxide group. At d 15 and again at d 21, rats from each group (n = 10) were placed in metabolism chambers and given 50 ml tap water over a 24-h period. Analysis of urine obtained from a metabolism-chamber study conducted after 15 d of consumption revealed concentrations of nicotine in the trans-nicotine N'-oxide group that were 3 times higher than cis-nicotine N'-oxide-treated animals. Urinary cotinine levels were similar in all three groups. Results from a second chamber study (d 21) showed similar urinary nicotine and cotinine values in all treatment groups. Plasma total triiodothyronine (TT3) concentrations were reduced in all treatment groups during the first week. Plasma total thyronine (TT4) concentrations were reduced (p less than 0.05) in the trans-nicotine N'-oxide and cis-nicotine N'-oxide treatment groups during the first week. Plasma total thyronine (TT4) concentrations cis-nicotine N'-oxide is presented. An analytical method for separation of nicotine, cotinine, and cis- and trans-nicotine N'-oxide, as well as cis- and trans-nicotine N,N'-dioxide, is also outlined.

Age Factors↗

The delivery and uptake of nicotine from an aerosol rod.

Nicotine aerosol rods were assessed for their possible usefulness as substitutes for cigarettes. Under standard FTC conditions, the per puff delivery of the aerosol rod averaged 0.3 micrograms nicotine/puff after 10 puffs and 6.4 micrograms nicotine/puff after 60 puffs. After puffing on the rods, no nicotine was detected in the plasma or urine of seven subjects.

Aerosols↗

Serum cotinine as a measure of tobacco smoke exposure in children.

To document passive smoke exposure, we measured concentrations of serum cotinine, a major metabolite of nicotine, in 38 young children and compared the results with the smoking histories of home residents. Cotinine was detected in 26 children (68%), of which ten had no household exposure according to a questionnaire. The serum cotinine concentration was significantly elevated in blacks compared with whites after controlling for the number of smokers in the home. After stratifying by race, there was a significant direct correlation between the serum cotinine concentration and the number of smokers in the home, the amount smoked by the mother, and the amount smoked by others in the home. We conclude that the serum cotinine concentration is a useful indicator of the actual exposure of young children to tobacco smoke and that unexplained racial differences in cotinine levels exist.

Black or African American↗

Cigarette smoking as a risk for cardiovascular disease. Part VI. Compensation with nicotine availability as a single variable.

In a biochemical investigation of human smoking behavior with filter cigarettes with high draw resistance that varied only in nicotine yield, we attempted to determine which nicotine levels provide desired nicotine intake with a minimum of physiologic and biochemical consequences. Twelve prescreened subjects were divided into two study groups and supplied with cigarettes that varied in nicotine delivery. Both groups were initially monitored while smoking their usual cigarette. At the following visit, smokers in group 1 received incremental increases and smokers in group 2 received incremental decreases in nicotine levels in assigned cigarettes. All subjects were monitored upon first exposure, after 1 week of acclimatization to each experimental cigarette, and upon return to their usual brands. Subjects in both groups were unable to compensate fully for their nicotine uptake from the lowest nicotine cigarette. In subjects in group 1, new nicotine baselines began to develop after 1 week of acclimatization to cigarettes containing 0.9 and 1.3 mg nicotine. New baseline nicotine levels were also noted in subjects receiving decreases in nicotine (group 2) after smoking the cigarette containing 1.3 mg nicotine for 1 week. Carboxyhemoglobin concentrations did not differ from those measured after the usual-brand cigarettes. Plasma cotinine concentrations increased as nicotine content per cigarette increased, except when subjects smoked a 1.3 mg nicotine cigarette. Plasma thiocyanate levels did not vary in either group. Systolic and diastolic blood pressures were generally not different from control values.

Adult↗

Biomedical applications of cotinine quantitation in smoking related research.

Two studies were undertaken to assess the variability of cotinine concentrations in different biological fluids and to determine the most desirable fluid to use for specific experimental protocols. For protocols validating smoking cessation, plasma or urinary cotinine determinations provided the most accurate indicators of compliance. In studies where smokers switched from high yield to low yield cigarettes, plasma cotinine determinations were good indicators of smoker behavior. Correct interpretation of smoker status is dependent on the biological fluid selected for cotinine analysis.

Cotinine↗

New aspects of tobacco carcinogenesis.

In tobacco smoke, catechols represent a major group of cocarcinogens. Model studies have indicated that polyphenols and polysaccharides are two major groups of precursors for the catechol formation during smoking. Results from the application of BP together with catechol on mouse skin indicate that the detoxification path of BP metabolism is decreased and the formation of the BP-7,8-diol is increased in comparison to the metabolism pattern observed when BP is applied alone. It remains to be demonstrated that the increased BP-7,8-diol formation leads also to increased formation of BP-DNA adducts in epithelial tissues. The nicotine-derived N-nitrosamines represent a major group of carcinogens in chewing tobacco, snuff, and tobacco smoke. Their concentrations in processed tobacco and smoke exceed by far those of carcinogenic nitrosamines in other environmental materials. Whereas it has been shown that nicotine gives rise to NNN and NNK during tobacco chewing, the endogenous formation of these potent carcinogens upon smoke inhalation has so far not been demonstrated. However, the formation of N-nitrosoproline in cigarette smokers and snuff dippers proves that smoke and snuff have a measurable potential for the endogenous formation of carcinogenic nitrosamines. Finally, the data presented here indicate that the individuals subjected to passive smoke exposure under controlled conditions take up measurable amounts of particulate matter. The nicotine level in the saliva of nonsmokers reflect recent passive smoke exposure and levels of nicotine and cotinine in urine reflect the long-term exposure to smoke particulates. The indicators, measured in saliva and serum, make it clear that uptake of particulates due to passive smoke exposure corresponds only to a low percentage (less than 2%) of the particulates that represent the uptake of a 1 pack-a-day adult smoker. However, in special settings, such as in the exposure of infants to the smoke pollutants generated by their mothers, uptake of smoke constituents can reach levels which raise concerns as to possible long range toxic effects. A broader base of subjects and a wider range of pollution situations need to be tested in order to substantiate the significance of the dosimetry of uptake executed to date. Such measurements constitute an attempt at more accurate risk assessment for nonsmokers in smoke polluted environments.

Animals↗