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N Benowitz

Publications and source records attributed to N Benowitz.

At least 19 recordsLinked to original sources
PubMed2001

Predictors of cotinine levels in US children: data from the Third National Health and Nutrition Examination Survey.

STUDY OBJECTIVE: To determine what factors predict cotinine levels in US children. DESIGN: Cross-sectional study. SUBJECTS: Nationally representative sample of 5,653 US children, both with and without reported tobacco smoke exposure in their homes. METHODS: We stratified the children into those with reported passive smoke exposure at home and those without this exposure. We used regression models to predict the log of the cotinine level of the participants with the following independent covariates: age; race/ethnicity; number of rooms in the home; sex; parental education; family poverty index; family size; region; and, among children with reported passive smoke exposure, the number of cigarettes smoked in the home. RESULTS: Children exposed to passive smoke had a mean cotinine level of 1.66 ng/mL, and children not exposed to passive smoke had a mean level of 0.31 ng/mL. Among children with reported smoke exposure, non-Mexican-American race/ethnicity, young age, low number of rooms in the home, low parental education, and an increasing number of cigarettes smoked in the home were predictors of increased serum cotinine levels. Among children with no reported smoke exposure, significant predictors of increased cotinine levels included black race, young age, Midwest region of the United States, low number of rooms in the home, low parental education, large family size, and low family poverty index. CONCLUSION: While the reported number of cigarettes smoked in the home is the most important predictor of cotinine levels in children exposed to smoke and may provide an opportunity for clinical intervention, other demographic factors are important among children both with and without reported smoke exposure.

Adolescent↗
PubMed2000

Diagnosis and treatment of nicotine dependence with emphasis on nicotine replacement therapy. A status report.

Tobacco use is a global health care problem. Repetitive exposure to nicotine produces neuroadaptation resulting in nicotine dependence. Cigarette smoking is particularly addictive due to the repeated delivery of bolus doses of nicotine to the bloodstream. Although compulsive tobacco use is sustained by nicotine addiction, it is the toxic combustion products in tobacco smoke such as carbon monoxide and oxidant gases that adversely affect the cardiovascular system. Smoking cessation produces significant health benefits and is a very cost-effective intervention. Evidence that nicotine is the addictive component of tobacco provides the rationale for using nicotine replacement therapy to aid cessation. Nicotine replacement therapy doubles successful smoking cessation rates and evidence-based guidelines for the treatment of tobacco addiction recommend routine use of nicotine replacement therapy, particularly in heavily dependent smokers. Success rates of up to 40% can be achieved in specialist clinics. Despite early concerns regarding the safety of nicotine replacement therapy in smokers with heart disease, it is now clear that the health risks of using nicotine replacement therapy to assist such patients to stop, or significantly reduce, smoking far outweigh any treatment-related risks.

Administration, Cutaneous↗
PubMed1999

Caffeine consumption and menstrual function.

The relation between caffeine intake and menstrual function was examined in 403 healthy premenopausal women who belonged to Kaiser Permanente Medical Care Program in 1990-1991. A telephone interview collected information about caffeinated beverage intake as well as other lifestyle, demographic, occupational, and environmental factors. Subjects collected daily urine samples and completed a daily diary for an average of five menstrual cycles. Metabolites of estrogen and progesterone were measured in the urine, each cycle was characterized as anovulatory or ovulatory, and a probable day of ovulation was selected when appropriate. Logistic regression and repeated measures analyses were performed on menstrual parameters. Women whose caffeine consumption was heavy (>300 mg of caffeine per day) had less than a third of the risk for long menses (> or =8 days) compared with women who did not consume caffeine (adjusted odds ratio = 0.30, 95% confidence interval 0.14-0.66). Those whose caffeine consumption was heavy also had a doubled risk for short cycle length (< or =24 days) (adjusted odds ratio = 2.00, 95% confidence interval 0.98-4.06); this association was also evident in those whose caffeine consumption was heavy who did not smoke (adjusted odds ratio = 2.11, 95% confidence interval 1.03-4.33). Caffeine intake was not strongly related to an increased risk for anovulation, short luteal phase (< or =10 days), long follicular phase (> or =24 days), long cycle (> or =36 days), or measures of within-woman cycle variability.

Adult↗
PubMed1998

Importance of chronopharmacokinetics in design and evaluation of transdermal drug delivery systems.

Circadian and meal effects on nicotine kinetics determine in part blood nicotine concentrations and in doing so may influence cigarette smoking behavior throughout the day. We have shown previously that nicotine clearance varies by approximately 17% (from peak to through) due to diurnal factors throughout the day and that meals increase nicotine clearance by about 42%. Until now pharmacokinetic analyses of nicotine absorption from patches have assumed a constant clearance of nicotine over 24 hr. Using 11 individual kinetic estimates from a previous study, we analyzed plasma nicotine concentrations vs. time data of two nicotine patch studies, and conducted a set of simulations to determine the extent to which time-varying kinetics would influence the design of transdermal drug delivery systems, intented to maintain a constant plasma nicotine concentration over 24 hr. Not incorporating time-varying kinetics leads to biased estimates of the delivery rate of the nicotine patches, and increases the variability in the delivery rates estimates. The hypothetical transdermal drug delivery systems designed assuming constant nicotine clearance results in a systematical underdosing during the first 12 hr after beginning therapy. The transdermal drug delivery systems obtained assuming the correct time-varying clearance shows three components: 1) an early high delivery rate, followed by 2) a rather constant, but slightly decreasing at night, release rate and 3) transient increases in delivery rate for 2 hr after each meal. The effect of circadian variations in clearance could be compensated for in patch design by decreasing the delivery rate during the night. Transient variations in clearance due to meals would require the corresponding use of rapid drug delivery dosage forms. The methods we devise to predict optimal dosing regimens in presence of chronopharmacokinetics might be useful for other medications in which blood levels need to be precisely controlled.

Administration, Cutaneous↗
PubMed1997

Cotinine effects on nicotine metabolism.

BACKGROUND: Nicotine clearance and half-life are known to be significantly reduced in smokers compared to nonsmokers. Cotinine is the major primary metabolite of nicotine, and it accumulates in the body with regular smoking. Nicotine and cotinine appear to be metabolized by the same liver enzyme. Therefore we hypothesized that cotinine inhibits nicotine metabolism, resulting in slower nicotine clearance in smokers compared with nonsmokers. METHODS: This was a crossover, randomized, double-blind, and placebo-controlled study. The subjects were 12 healthy nonsmoking volunteers. They received two intravenous infusions of deuterium-labeled nicotine-d2 and cotinine-d4 (0.5 micrograms/kg/min), once with oral cotinine treatment of 0.25 mg/kg twice a day and once with placebo. Nicotine and cotinine pharmacokinetic parameters were determined for each infusion. RESULTS: During oral cotinine treatment, average plasma levels of cotinine ware 900 ng/ml, comparable to levels observed in some very heavy smokers. Cotinine had no effect on the disposition kinetics of nicotine-d2. The half-life of cotinine after low-dose cotinine-d4 infusion was comparable to that after high-dose cotinine described in previous studies. The half-life of labeled cotinine derived from nicotine was significantly longer than the half-life of cotinine administered as cotinine. CONCLUSIONS: Cotinine is not responsible for the lower nicotine clearance observed in smokers. Our data suggest that the pharmacokinetics of low-dose cotinine in nonsmokers do not differ from those of high-dose in smokers, and therefore cotinine levels can be used quantitatively in environmental tobacco exposure. The longer half-life of cotinine derived from nicotine suggests that slow release of nicotine from tissues is responsible for the apparent long half-life of cotinine in nonsmokers exposed to environmental tobacco smoke.

Adult↗
PubMed1997

Caffeinated beverages, decaffeinated coffee, and spontaneous abortion.

We examined the relations between spontaneous abortion and the consumption of caffeine, individual caffeine-containing beverages (coffee, tea, and soda), and decaffeinated coffee in a prospective study of 5,144 pregnant women. We collected information about potential risk factors for spontaneous abortion, including consumption of caffeinated beverages and decaffeinated coffee before and during pregnancy, by interview in the first trimester. Neither total estimated caffeine nor individual caffeinated beverage consumption during the first trimester was associated with an appreciable increase in risk for spontaneous abortion. The adjusted odds ratio for consumption of greater than 300 mg per day of caffeine was 1.3 [95% confidence interval (CI) = 0.8-2.1] after adjustment for maternal age, pregnancy history, cigarette and alcohol consumption, employment, race, gestational age at interview, and marital and socioeconomic status. The adjusted odds ratio for spontaneous abortion related to consumption of three or more cups of decaffeinated coffee during the first trimester was 2.4 (95% CI = 1.3-4.7) in the same model. Although we could not demonstrate this with available data, we suspect that this association was due to bias resulting from the relations among fetal viability, symptoms of pregnancy such as nausea, and consumption patterns during pregnancy.

Abortion, Spontaneous↗
PubMed1997

What should be the elements of any settlement with the tobacco industry?

Litigation and regulatory assaults on the tobacco companies may create a willingness among tobacco manufacturers to bargain resources and acceptance of public policy changes for limitations of liability, as has been seen by the recent settlement with the Liggett Group. Two elements absolutely critical to any plan are the elimination of tobacco advertising and promotion and the removal of addiction as a reason for tobacco use. Minimal components of any settlement should include: (a) acceptance by the tobacco manufacturers of the causal relationship between tobacco use and disease, and the addictive nature of nicotine; (b) a total ban on tobacco advertising and promotion; (c) FDA jurisdiction over tobacco products and their nicotine content, with the intent of removing nicotine as soon as acceptable nicotine substitution products are available; (d) reimbursement to the states for Medicaid and other state expenditures attributable to smoking, to the maximum extent feasible; (e) funding for local, state, and federal programmes and research in tobacco control; (f) acceptance of legislation and regulations protecting the right of non-smokers to breathe air free of tobacco smoke; (g) funding for a large, national, media-led, anti-tobacco campaign; and (h) cessation assistance for addicted smokers. If negotiations toward a settlement proceed, it is essential that the public health community participate in defining the elements of any agreement to ensure that whatever agreement develops is focused on reducing tobacco-related disease rather than continuing the profitability of American tobacco companies. That participation requires articulation of the core elements essential to an acceptable agreement. If resolution of the public health issues surrounding continued sale of tobacco products can be reached in the United States, it may provide a model for similar resolution in other countries.

Adolescent↗
PubMed1996

Chronopharmacokinetics of nicotine.

RATIONALE: For high-clearance drugs such as nicotine, hemodynamic changes throughout the day may be expected to influence the rate of metabolism. MATERIAL AND METHODS: To assess the effects of meals and diurnal rhythms on nicotine clearance, an intravenous infusion of nicotine bitartrate was administered for 48 hours to 11 subjects. Two models to determine nicotine clearance variation throughout the day are described. Both models were used to estimate the mean effect of meal and diurnal rhythms on nicotine clearance and individual parameters that were regressed against baseline covariates. Clearance was modeled as a function of time [CL(t)] and split it in three components: a (constant) baseline value (theta 1), its circadian (diurnal) variation, and the effect of meal: CL(t) = [theta 1 + circadian(t)] [1 + meal(t)]. A two-compartmental (time-variant) model incorporating CL(t) was then fitted to the data providing estimates of CL(t) conditional on literature values of the time-invariant parameters (volume of distribution and intercompartmental clearances). RESULTS: The estimated circadian(t) showed a maximum at approximately 11 AM and a flat minimum from 6 PM to 3 AM; the estimated meal(t) showed a sharp increase up to 1 hour (after the meal), at which point clearance is increased 42%, and a slower decrease thereafter, returning to baseline (zero) after 2.8 hours. Individual estimates of baseline clearance are found to have a linear relationship with body weight. No other covariate, sex in particular, effect could be found.

Adult↗
PubMed1996

Society for Research on Nicotine and Tobacco.

The proceedings of the inaugural scientific meeting of the Society for Research on Nicotine and Tobacco (SRNT) are summarized. The primary objective of the meeting was to foster the exchange of information on the effects of nicotine and tobacco use, as well as factors which influence their use, drawing from biological, behavioral and social sciences. Much of this research can be viewed as a tale of "two" drugs--nicotine as a key to an important public health problem, and nicotine as a classical tool of physiological and pharmacological research. A historical overview of research on "both" drugs is provided first. Public policy alternatives for reducing the prevalence of tobacco use have been derived in part from basic and clinical research results and are briefly outlined. Evidence for genetic determinants on nicotine use and effects is presented using data from twin studies and from molecular genetic research with humans and animals. Consistent with this research, there is evidence of individual differences in pharmacokinetics and effects of nicotine, which could account for differences in smoking behavior and nicotine dependence. Finally, recent developments in the therapeutic uses of nicotine and novel nicotinic agonists with schizophrenia, Alzheimer's disease, Parkinson's disease, Tourette's syndrome and ulcerative colitis are presented. Overall, the research presented at the meeting demonstrated the vast diversity of areas of study involving nicotine and tobacco, as well as the rich opportunities for cross-communication among researchers from different disciplines.

Animals↗
PubMed1996

Predictors of carbon monoxide and hydrogen cyanide exposure in smoke inhalation patients.

OBJECTIVE: A prospective study of civilian (nonfirefighter) smoke inhalation patients was carried out to test the hypotheses that: 1) absorption of carbon monoxide and hydrogen cyanide from smoke can be predicted by clinical examination and historical data; and, more specifically 2) a history of exposure to burning synthetic polymers is an important predictor of systemic cyanide levels. METHODS: The study was conducted over a three-year period at six urban hospitals. Patients with or without burns who were exposed to smoke within five hours of hospital arrival were sampled for carboxyhemoglobin, whole blood cyanide, urine cotinine and urine creatinine. Controls consisted of a smaller group of smoking status-matched, nonsmoke-exposed burn patients. ANALYSIS: Historical information was obtained on SMOKING status, FIRETYPE (structural vs other), MATERIAL burned (natural vs synthetic) and LAGTIME (from exposure to sampling). A smoke inhalation SCORE (0-10) was assigned to each case, based on physical examination findings and changes on chest X ray, and carboxyhemoglobin and cyanide levels were entered into various multivariate linear regression models. RESULTS: A total of 40 cases and 9 controls were recruited, ranging in age from 15 to 92 years. Thirty-four cases were discharged alive and six expired in-hospital. Observed carboxyhemoglobin levels ranged from 1.2% to 41.6% in cases (mean 8.6%), and from 0.5 to 7.3% in controls (mean 2.9%). Observed cyanide levels ranged from nondetectable (< 0.05 micrograms/mL) to 2.79 micrograms/mL in cases (mean 0.25 micrograms/mL), and from nondetectable to 0.11 micrograms/mL in controls (mean 0.03 micrograms/mL). Among cases, linear regression models explained up to 35% of the observed variance in carboxyhemoglobin levels (p < 0.001) and up to 48% of the variance in cyanide levels (p = 0.0001). CONCLUSIONS: SCORE was the strongest predictor of both carboxyhemoglobin and cyanide levels; LAGTIME also explained significant variance for [log-transformed] carboxyhemoglobin. Historical factors, such as FIRETYPE, MATERIAL, and SMOKING status, did not explain significant variance in most of the statistical models employed.

Adolescent↗
PubMed1996

Neural and endocrine circuits mediating inhibition of bradykinin-induced plasma extravasation by subcutaneous and spinal-intrathecal nicotine.

In this study we evaluated the mechanisms underlying s.c. and spinal intrathecal (i.t.) nicotine inhibition of bradykinin-induced plasma extravasation in the knee joint of the rat (J. Pharmacol. Exp. Ther. 262: 889-895, 1992; ibid., 264: 839-844, 1993). The dose-response curve for the inhibitory action of s.c. nicotine on bradykinin-induced plasma extravasation was attenuated by adrenal medullectomy and by intra-articular perfusion of ICI-118,551 (a beta-2 adrenoceptor antagonist). In addition, the dose-response curve of s.c. nicotine was attenuated by acute surgical lumbar sympathectomy and by intra-articular phentolamine (an alpha adrenoceptor antagonist). The dose-response curve for i.t. nicotine (up to 1 mg/kg) was not attenuated by intra-articular ICI-118,551 and was potentiated by adrenal medullectomy. The action of i.t. nicotine was also not affected by intra-articular phentolamine or by acute surgical lumbar sympathectomy. These results suggest that the inhibition of bradykinin-induced plasma extravasation in the knee joint of the rat by s.c., but not i.t., nicotine is mediated through the sympathoadrenal and sympathetic systems.

Animals↗
PubMed1993

Saliva nicotine as an index of plasma levels in nicotine skin patch users.

This study examined whether salivary nicotine concentrations would provide a useful index of plasma concentrations in studies of the effects of transdermal nicotine administration. Twenty-four subject smokers abstained from smoking for 12 h prior to admission to a clinical research unit ward and for 36 h while remaining confined to the ward. Three doses of nicotine skin patches were applied to different groups of subjects, and blood and saliva samples were collected at several time points. Saliva flow was stimulated by three different methods: (a) sucking on a lemon candy, (b) dissolving a sugar cube in the mouth, and (c) chewing on parafilm. Nicotine and cotinine concentrations were measured in both saliva and blood using gas chromatography. There was a high correlation between blood and saliva values of nicotine (r = 0.82). Overall, saliva nicotine concentrations were approximately 8.1 times higher than those of plasma. Saliva and blood cotinine concentrations were also highly correlated (r = 0.94), replicating results of previous studies. Results suggest that saliva nicotine may be a useful marker of nicotine intake during nicotine skin patch treatment. Saliva collection may be advantageous under conditions in which blood collection is impractical and may provide greater sensitivity because of the high concentration of nicotine in saliva relative to that in blood.

Administration, Cutaneous↗
PubMed1992

Smokeless tobacco, cardiovascular risk factors, and nicotine and cotinine levels in professional baseball players.

BACKGROUND: The use of smokeless tobacco (ST), which has increased in popularity over the past 2 decades, results in considerable systemic exposure to nicotine. Nicotine might contribute to atherosclerosis by an effect on cardiovascular risk factors. METHODS: The effects of ST use on cardiovascular risk factors and cotinine and nicotine levels were studied in 1061 professional baseball players during spring training in 1988 and 1989. RESULTS: Of the study participants 477 (45%) were users. ST use was more common among Whites (55%) than among Blacks (29%) or Hispanics (21%), and users reported heavier consumption of alcohol (p less than .001) and had higher mean serum caffeine levels (p less than .001) than nonusers. ST users did not differ from nonusers in adjusted levels of systolic and diastolic blood pressure, pulse, and total or HDL-cholesterol. Among ST users, participants using snuff had higher mean serum cotinine levels than those who used chewing tobacco (p less than .001). There was no association between serum cotinine levels and adjusted levels of any cardiovascular risk factor studied. However, higher diastolic blood pressures were associated with higher mean serum nicotine levels (p = .02). CONCLUSIONS: Smokeless tobacco use has at most a modest effect on cardiovascular risk factors in young physically fit men.

Adult↗
PubMed1991

Amiloride improves hemodynamics in patients with chronic congestive heart failure treated with chronic digoxin and diuretics.

Potassium-sparing diuretics have been reported to decrease the positive inotropic effect of digoxin. We studied the hemodynamic effects of amiloride in patients taking digoxin for chronic heart failure. Eleven men with a history of congestive heart failure were studied in a double blind, cross-over, placebo controlled trial with the patients on digoxin alternating placebo with amiloride. After 7 days on the trial drug, a Swan-Ganz catheter was placed in the pulmonary artery and measurements made at rest and with increasing degrees of supine bicycle exercise. Right-sided and pulmonary artery wedge pressures and systemic arterial pressures, as well as cardiac outputs, were measured. After a 7 day washout period, placebo (P) and Amiloride (A) were switched and after 7 days on the therapy, a second hemodynamic study at rest and varying degrees of supine bicycle exercise was repeated. At rest there were no significant differences in the right-sided, pulmonary arterial wedge pressure or cardiac outputs between the patients on Amiloride (A) versus placebo (P). During exercise there were significant differences between (P) and (A) at the 50 watt-second stage of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1990

Oral therapy for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A controlled trial of trimethoprim-sulfamethoxazole versus trimethoprim-dapsone.

BACKGROUND: Antimicrobial drugs that can be taken orally are needed for the treatment of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). Preliminary data indicate that dapsone with trimethoprim may be an effective alternative to trimethoprim-sulfamethoxazole, which is frequently toxic. METHODS: In a double-blind trial, 60 patients with AIDS and mild-to-moderately-severe first episodes of P. carinii pneumonia (partial pressure of oxygen in arterial blood, greater than 60 mm Hg while breathing room air) were randomly assigned to 21 days of treatment with either trimethoprim-sulfamethoxazole (20 and 100 mg per kilogram of body weight per day, respectively) or trimethoprim-dapsone (20 mg per kilogram per day and 100 mg per day). RESULTS: The orally administered treatment failed because of progressive pneumonitis in 3 of the 30 patients assigned to trimethoprim-sulfamethoxazole and in 2 of the 30 assigned to trimethoprim-dapsone (P greater than 0.3). Major toxic effects required a switch to intravenous pentamidine for 17 patients (57 percent) in the trimethoprim-sulfamethoxazole group, as compared with 9 (30 percent) in the trimethoprim-dapsone group (P less than 0.025). With trimethoprim-sulfamethoxazole, there were more instances of severe chemical hepatitis (six, as compared with one in the trimethoprim-dapsone group) and marked neutropenia (five vs. one). Intolerable rash (three in each treatment group) and severe nausea and vomiting (two in each group) occurred with equal frequency with both drug combinations. Methemoglobinemia occurred in most of the patients treated with trimethoprim-dapsone, but it was asymptomatic and the level exceeded 20 percent in only one patient. Mild hyperkalemia (serum potassium level, 5.1 to 6.1 mmol per liter) also occurred in 53 percent of the patients treated with trimethoprim-dapsone. CONCLUSIONS: In patients with AIDS, oral therapy with trimethoprim-sulfamethoxazole and with trimethoprim-dapsone are equally effective for mild-to-moderate first episodes of P. carinii pneumonia, but with trimethoprim-dapsone there are fewer serious adverse reactions than with trimethoprim-sulfamethoxazole.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Smokeless tobacco use and health effects among baseball players.

The effects of smokeless tobacco (ST) use were studied in 1109 members of major and minor league professional baseball teams during spring training in 1988. The prevalence of current ST use was 39%. The median age at initiation among users was 18 years, and the median duration of use was 5 years. Among users, 75% cited a snuff brand as their usual ST product. Oral leukoplakia was present in 46% (196/423) of current-week ST users and 1.4% (7/493) of nonusers (odds ratio, 60; 95% confidence interval, 28 to 130). Prevalence of oral leukoplakia among ST users increased with hours used per day and decreased with time lapsed since last use, and was higher in snuff users than in chewing tobacco users. Of the subjects with oral leukoplakia who underwent punch biopsy, 91 had benign hyperkeratosis and one had mild dysplasia. Overall prevalence of dental caries, gingivitis, and plaque did not differ between ST users and nonusers. In analyses confined to facial surfaces of mandibular incisor teeth, where ST is most commonly used, there were significant increases among users in both gingival recession and attachment loss. Users of ST did not differ from nonusers in blood pressure, pulse, total or high-density lipoprotein cholesterol level, or white blood cell count, but among users high-density lipoprotein cholesterol levels were inversely associated with serum cotinine levels. The major health effects of ST use among professional baseball players are oral leukoplakia and localized periodontal disease. The study population was young, physically fit, and characterized by relatively moderate short-term ST use.

Adolescent↗