Cheryl Oncken - Academia.edu (original) (raw)

Papers by Cheryl Oncken

Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2015

Smokers may prefer menthol cigarettes to mask the bitter taste of nicotine. Variation in the tast... more Smokers may prefer menthol cigarettes to mask the bitter taste of nicotine. Variation in the taste receptor gene, TAS2R38, may contribute to preference for menthol cigarettes. To determine whether two common haplotypes of TAS2R38 (proline-alanine-valine [PAV] and alanine-valine-isoleucine [AVI]), which have been associated, respectively, with bitter taste or a lack of bitter taste produced by propylthiouracil, are associated with preference for menthol cigarettes. Data on smoking and blood for DNA extraction and genotyping were obtained from 323 pregnant non-Hispanic or Hispanic Caucasian smokers. We genotyped three TAS2R38 single nucleotide polymorphisms (rs713598, rs1726866, and rs10246939) and constructed haplotypes. We examined associations between menthol preference and the frequency and distribution of the AVI and PAV haplotypes among study participants. Participants smoked an average of 16 cigarettes per day before pregnancy. The PAV and AVI haplotype frequencies were 48% and...

OBJECTIVE: To estimate the safety and efficacy of treat- ment with 2-mg nicotine gum for smoking ... more OBJECTIVE: To estimate the safety and efficacy of treat- ment with 2-mg nicotine gum for smoking cessation during pregnancy. METHODS: Pregnant women who smoked daily re- ceived individualized behavioral counseling and random assignment to a 6-week treatment with 2-mg nicotine gum or placebo followed by a 6-week taper period. Women who did not quit smoking were instructed to reduce the

Because abnormalities in opioid neurotransmission appear to underlie some of the inherited risk f... more Because abnormalities in opioid neurotransmission appear to underlie some of the inherited risk for alcoholism, we examined the effects of naloxone, an opioid antagonist, on corticotropin and cortisol responses in nonalcoholic subjects differentiated by paternal history of alcoholism. Placebo-controlled, balanced, within-subject design involving 2 test days over a period of 3 to 7 days. Thirty-six subjects (67% male; 53% paternal-history-positive; mean age = 25.0 years) were screened to exclude substance abuse or dependence. Subjects received intravenous naloxone 125 microg/kg or placebo, with sessions in random order. Plasma corticotropin and cortisol were measured for up to 120 min post infusion. Corticotropin responses at baseline and following naloxone did not differ by paternal history of alcoholism; however, paternal-history-positive subjects exhibited greater cortisol concentrations at baseline, and at 15 and 30 min after naloxone administration. Paternal-history-positive subjects also had an earlier and greater peak cortisol response to naloxone and a nonsignificant trend for a greater area under the cortisol time curve than paternal-history-negative subjects. These findings suggest that individuals with greater vulnerability to alcoholism may have altered Hypothalamic-pituitary axis (HPA) dynamics, a finding that is consistent with a growing body of data on the role of opioidergic neurotransmission in the inherited risk of alcoholism.

While the pathologies associated with in utero smoke exposure are well established, their underly... more While the pathologies associated with in utero smoke exposure are well established, their underlying molecular mechanisms are incompletely understood. We differentiated human embryonic stem cells in the presence of physiological concentrations of tobacco smoke and nicotine. Using post hoc microarray analysis, quantitative PCR, and immunoblot analysis, we demonstrated that tobacco smoke has lineage-and stage-specific effects on human embryonic stem cell differentiation, through both nicotine-dependent and -independent pathways. We show that three major stem cell pluripotency/differentiation pathways, Notch, canonical Wnt, and transforming growth factor-β, are affected by smoke exposure, and that Nodal signaling through SMAD2 is specifically impacted by effects on Lefty1, Nodal, and FoxH1. These events are associated with upregulation of microRNA-302a, a post-transcriptional silencer of Lefty1. The described studies provide insight into the mechanisms by which tobacco smoke influences fetal development at the cellular level, and identify specific transcriptional, post-transcriptional, and signaling pathways by which this likely occurs.

Smoking during pregnancy is a significant public health concern. Maternal smoking increases the r... more Smoking during pregnancy is a significant public health concern. Maternal smoking increases the risk of spontaneous abortion, low birth weight, premature delivery, sudden infant death syndrome and learning and behavioral problems in the offspring. Unfortunately, the majority of pregnant women do not quit smoking during pregnancy. Although pharmacotherapy may improve smoking cessation rates in pregnancy, very few studies exist that have studied the safety and efficacy of medications to treat pregnant smokers. This article reviews the available safety and efficacy data for the use in pregnancy of the five first-line therapies and two second-line therapies that are recommended for smoking cessation in non-pregnant smokers. Other promising nicotine replacement therapies are also reviewed. Ultimately, the choice whether to use pharmacotherapy for smoking cessation should be made jointly by the pregnant smoker and her health care provider. This article reviews factors that may be considered when prescribing pharmacotherapy to pregnant smokers (i.e. the role of behavioral counseling, identification of appropriate patients, potential advantages and disadvantages of each of the pharmacotherapies, proposed monitoring strategies, dose and duration and goals of treatment). More research regarding the safety and efficacy of pharmacotherapy during pregnancy is needed to define the risk/benefit profile of each medication for use in smoking cessation in pregnant women. [Oncken CA, Kranzler HR. Pharmacotherapies to enhance smoking cessation during pregnancy. Drug Alcohol Rev 2003;22:191 -202]

Nicotine & Tobacco Research, 2006

To date, we have no valid biomarkers that serve as proxies for tobacco-related disease to test po... more To date, we have no valid biomarkers that serve as proxies for tobacco-related disease to test potential reduced exposure products. This paper represents the deliberations of four workgroups that focused on four tobacco-related heath outcomes: Cancer, nonmalignant pulmonary disease, cardiovascular disease, and fetal toxicity. The goal of these workgroups was to identify biomarkers that offer some promise as measures of

Psychiatric Clinics of North America, 1999

Journal of Maternal-fetal & Neonatal Medicine, 2009

Objective-To examine the short-term effects of the nicotine patch or nasal spray on measures of n... more Objective-To examine the short-term effects of the nicotine patch or nasal spray on measures of nicotine exposure, withdrawal symptoms, and on maternal and fetal heart rates in pregnant smokers.

Obstetrical & Gynecological Survey, 1997

To compare blood concentrations of nicotine and cotinine and maternal and fetal hemodynamic effec... more To compare blood concentrations of nicotine and cotinine and maternal and fetal hemodynamic effects resulting from use of nicotine gum versus cigarette smoking in pregnant smokers. Pregnant women (24 to 36 weeks' gestation) who smoked chronically were randomly assigned with a 1:2 randomization scheme to either a group that smoked cigarettes (n = 10) or to a group that stopped smoking and chewed at least six pieces of nicotine gum (2 mg nicotine per piece) per day (n = 19). Blood nicotine and cotinine concentrations, maternal heart rate and blood pressure, uterine resistance index, and fetal heart rate and umbilical artery resistance index were obtained before and after one cigarette was smoked at baseline and after 5 continuous days of either chewing gum or smoking. A significant reduction from baseline in nicotine (p < 0.0001) and cotinine (p < 0.0025) concentrations was observed in those who chewed nicotine gum compared with those who smoked cigarettes. No significant differences in the changes in maternal or fetal hemodynamic parameters from baseline to estimated time of peak nicotine exposure were observed between those who smoked cigarettes and those who chewed nicotine gum. Short-term use of nicotine gum delivers less nicotine than usual cigarette smoking in pregnant women.

Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2015

Electronic cigarettes (e-cigarettes) represent an emerging public health issue. These devices del... more Electronic cigarettes (e-cigarettes) represent an emerging public health issue. These devices deliver nicotine along with other constituents, including flavorants, via an inhalable aerosol. Their uptake is rapidly increasing in both adults and youths, primarily among current smokers. Public debate is increasing on how these devices should be regulated and used, yet only limited peer-reviewed research exists. To develop a informed policy for e-cigarettes, their effects on human behavior, physiology, and health need to be understood. This paper describes proceedings from a National Institutes of Health-sponsored workshop, which was held in November 2013, to identify research needs related to the effects of e-cigarettes. Discussion topics included e-cigarette risks and abuse potential; the potential role for e-cigarettes in harm reduction and smoking cessation; unintended consequences of e-cigarette use, such as becoming a gateway to conventional cigarettes; and dual use of both e-ciga...

Tobacco Control, 2000

Background In the USA, of the four million women who deliver babies each year, approximately 0.8–... more Background In the USA, of the four million women who deliver babies each year, approximately 0.8–1 million smoke during their pregnancies. Smoking has a substantial adverse impact on pregnancy outcomes including growth retardation, preterm birth, ...

Thorax, 2008

Background: Varenicline, a new treatment for smoking cessation, has demonstrated significantly gr... more Background: Varenicline, a new treatment for smoking cessation, has demonstrated significantly greater efficacy over placebo and sustained release bupropion (bupropion SR). A study was undertaken to compare a 12-week standard regimen of varenicline with a 10

Psychopharmacology, 2001

Rationale: Naltrexone treatment of alcohol dependence is associated with adverse events that may ... more Rationale: Naltrexone treatment of alcohol dependence is associated with adverse events that may limit its effectiveness. Consequently, understanding the impact of adverse events on medication compliance and treatment retention may enhance naltrexone therapy of alcoholism. Objectives: To examine the relations among adverse events, drinking behavior, medication compliance and study retention in alcoholics receiving naltrexone for relapse prevention. Methods: The current report is based on analysis of data from 92 subjects who participated in two previously published studies. Moderate or severe adverse effects were monitored weekly and categorized as either neuropsychiatric (NP) or gastrointestinal (GI). Medication compliance was determined by weekly urinary riboflavin testing. Study retention was determined by the proportion of study weeks completed by the subject. The causal relations among adverse events, medication compliance and study retention were analyzed separately for NP and GI adverse events using regression-based recursive path models. Results: Both the NP and GI models fit the data well [NP model: χ 2 (4)=0.59, P=0.96; GI model: χ 2 (4)=2.81, P=0.59]. NP adverse events exerted little influence on medication compliance (β=-0.17, P=0.071), but directly decreased the length of study retention (β=-0.35, P<0.001). In contrast, there was a significant impact of GI adverse events on medication compliance (β=-0.29, P=0.002), but not directly on study retention (β=-0.14, P=0.081). Conclusion: Future studies aimed at enhancing the effectiveness of naltrexone should examine ways of reducing both NP and GI adverse events, in order to enhance both medication compliance and treatment retention.

Pharmacology Biochemistry and Behavior, 1997

of cotinine in humans: physiologic, subjective, and cognitive effects. PHARMACOL BIOCHEM BEHAV 57... more of cotinine in humans: physiologic, subjective, and cognitive effects. PHARMACOL BIOCHEM BEHAV 57(4) [643][644][645][646][647][648][649][650] 1997.-Preliminary data suggest that cotinine, the major metabolite of nicotine, may be behaviorally active. Studies involving the administration of cotinine at doses that produce high blood concentrations (in excess of those produced by cigarette smoking) may be of interest. This inpatient, 10-day human study examined the safety and the effects from several high doses of oral cotinine fumarate (40, 80, or 160 mg) or placebo in abstinent cigarette smokers. All subjects smoked cigarettes ad lib during the first 2 days of the study, then were required to be abstinent beginning on the third day. All subjects were given placebo on this day to wash out nicotine before the administration of cotinine. Subjects were subsequently randomly assigned in a doubleblind manner to cotinine or placebo for the next 3 days to determine the safety profile of cotinine. All subjects were given placebo on the final 3 days to examine cotinine withdrawal symptoms. The results showed no significant physiologic, subjective, or performance effects across the various doses of cotinine and placebo. Furthermore, no cotinine withdrawal effects were observed. This study demonstrates that short-term administration of cotinine to humans at levels as high as 10 times that attained from cigarette smoking is safe with no observable acute or withdrawal effects from cotinine in this setting. © 1997

Pediatric Research, 2008

Maternal smoking doubles the risk of delivering a low birth weight infant.

Pediatric Research, 2003

The aim of this study was to compare catecholamine concentrations in the fetal umbilical artery c... more The aim of this study was to compare catecholamine concentrations in the fetal umbilical artery cord blood from the offspring of smokers versus the offspring of nonsmokers. Pregnant women who were self-identified as smokers (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;/=10 cigarettes per day throughout pregnancy) or nonsmokers were recruited for study participation. Maternal blood was collected for cotinine concentrations. Umbilical artery cord blood was collected at delivery for arterial pH and catecholamine concentrations. Cord blood was obtained from 51 subjects, including 21 smokers and 30 nonsmokers. Median epinephrine concentrations [304 pg/mL versus 597 pg/mL (Mann-Whitney U = 170; p = 0.006)] and median norepinephrine concentrations [3148 pg/mL versus 6558 pg/mL (Mann-Whitney U = 191; p = 0.006)] were significantly lower in smokers compared with nonsmokers, respectively. After controlling for gestational age, route of delivery, and arterial pH, log-transformed epinephrine concentrations between smokers and nonsmokers were statistically significant (p = 0.03), with a similar trend for log-transformed norepinephrine concentrations (p = 0.07). Analyses of the data using cotinine &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;20 ng/mL to classify nonsmokers also showed differences in epinephrine concentrations between groups (p = 0.02). These results are consistent with results from animal studies showing that catecholamine concentrations may be affected by prenatal nicotine exposure. Further studies are needed to validate these findings and to examine the specific mechanism by which these differences may arise.

Patient Education and Counseling, 2006

Objective: Rates of cigarette smoking are higher among women who receive obstetric care through p... more Objective: Rates of cigarette smoking are higher among women who receive obstetric care through publicly funded prenatal clinics. This study compared smoking outcomes for pregnant women (n = 105) who were randomized to receive either usual care (standard cessation advice from the health care provider) or an intervention conducted in the prenatal clinic consisting of 1.5 h of counseling plus telephone follow-up delivered by a masters prepared mental health counselor. Methods: Subjects were 105 low income, predominantly Hispanic, pregnant patients in an urban prenatal clinic. Smoking outcomes were assessed at end of pregnancy and 6 months post-partum. Results: At follow-up, 28.3% and 9.4% of participants in the experimental intervention and 9.6% and 3.8% of patients in usual care were abstinent at end of pregnancy ( p = .015) and 6 months post-partum, respectively ( p = .251). Cost of the intervention was 56perpatientandcosttoproduceanon−smokeratendofpregnancywas56 per patient and cost to produce a non-smoker at end of pregnancy was 56perpatientandcosttoproduceanon−smokeratendofpregnancywas299. Conclusions: This model for intervention was cost-effective and was associated with significantly lower smoking rates at end of pregnancy. Practical implications: If these findings are replicated, prenatal clinics could offer the option for intensive smoking cessation treatment by training mental health counselors to deliver one extended smoking cessation counseling session. #

Obstetrics & Gynecology, 1997

Obstetrics & Gynecology, 2002

To evaluate the effect of repeated cigarette smoking on fetal heart rate (FHR) characteristics. F... more To evaluate the effect of repeated cigarette smoking on fetal heart rate (FHR) characteristics. Fifteen chronic smokers who were between 28 and 36 weeks&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; gestation were evaluated during an 8-hour smoking session. Baseline FHR and reactivity were evaluated before an initial cigarette and 4 hours later (after the fourth cigarette), when the effects of smoking on FHR were expected to be maximal. Plasma nicotine was measured at baseline and repeated at times of fetal monitoring. Subjects smoked a mean +/- standard deviation of 22 +/- 6 cigarettes per day. They abstained from smoking for 9.2 +/- 3.2 hours before evaluation. The initial baseline FHR was 134 +/- 9 beats per minute versus 135 +/- 11 beats per minute after the fourth cigarette (P =.17). Plasma nicotine increased from 2.6 +/- 5.6 ng/mL to 24 +/- 9.9 ng/mL after the fourth cigarette (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.001). The initial nonstress test was reactive in 12 of 15 (80%) of the fetuses. After the fourth cigarette, only four of 15 (27%) of the nonstress tests were reactive. A majority of tracings (eight of 15) were initially reactive before smoking and became nonreactive after smoking. Some tracings remained nonreactive (three of 15), and some tracings remained reactive (four of 15) at both assessments. None of the tracings that were initially nonreactive became reactive. The change in reactivity was significant (P =.013). Acute, repeated smoking decreases FHR reactivity.

Nicotine & Tobacco Research, 2014

Topiramate (TOP) blocks glutamate receptors and facilitates GABA (γ-aminobutyric acid) neurotrans... more Topiramate (TOP) blocks glutamate receptors and facilitates GABA (γ-aminobutyric acid) neurotransmission, effects that may facilitate smoking cessation. We compared the effects of behavioral counseling combined with (a) TOP, (b) TOP/nicotine patch (TOP/NIC), or (c) placebo (PLC) for smoking cessation. We conducted a 10-week randomized trial in which subjects and research personnel were blinded to TOP versus PLC but not to the TOP/NIC patch condition. In groups receiving TOP, the medication dosage was titrated gradually up to 200 mg/day. The smoking quit date (QD) was scheduled after 2 weeks of medication treatment. NIC (21 mg) was started on the QD in subjects randomized to the TOP/NIC condition. The main outcome measure was the end-of-treatment, 4-week continuous abstinence rate (CAR; biochemically confirmed). Fifty-seven subjects were randomized to treatment. The 4-week CAR was 1 of 19 (5%) in the PLC group, 5 of 19 (26%) in the TOP group, and 7 of 19 (37%) in the TOP/NIC group (p = .056). Pairwise comparisons showed a difference between TOP/NIC and PLC (p = .042) and a nonsignificant difference between TOP and PLC (p = .18). The PLC group gained 0.37 lb/week, the TOP group lost 0.41 lb/week, and the TOP/NIC group lost 0.07 lb/week (p = .004). Pairwise comparisons showed a difference between TOP and PLC (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001) and between TOP/NIC and PLC groups (p = .035). Paresthesia was more frequent in subjects on TOP than PLC (p = .011). TOP, alone or in combination with the NIC, resulted in a numerically higher quit rate than PLC and decreased weight. A larger, PLC-controlled trial is needed to confirm these findings.

Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2015

Smokers may prefer menthol cigarettes to mask the bitter taste of nicotine. Variation in the tast... more Smokers may prefer menthol cigarettes to mask the bitter taste of nicotine. Variation in the taste receptor gene, TAS2R38, may contribute to preference for menthol cigarettes. To determine whether two common haplotypes of TAS2R38 (proline-alanine-valine [PAV] and alanine-valine-isoleucine [AVI]), which have been associated, respectively, with bitter taste or a lack of bitter taste produced by propylthiouracil, are associated with preference for menthol cigarettes. Data on smoking and blood for DNA extraction and genotyping were obtained from 323 pregnant non-Hispanic or Hispanic Caucasian smokers. We genotyped three TAS2R38 single nucleotide polymorphisms (rs713598, rs1726866, and rs10246939) and constructed haplotypes. We examined associations between menthol preference and the frequency and distribution of the AVI and PAV haplotypes among study participants. Participants smoked an average of 16 cigarettes per day before pregnancy. The PAV and AVI haplotype frequencies were 48% and...

OBJECTIVE: To estimate the safety and efficacy of treat- ment with 2-mg nicotine gum for smoking ... more OBJECTIVE: To estimate the safety and efficacy of treat- ment with 2-mg nicotine gum for smoking cessation during pregnancy. METHODS: Pregnant women who smoked daily re- ceived individualized behavioral counseling and random assignment to a 6-week treatment with 2-mg nicotine gum or placebo followed by a 6-week taper period. Women who did not quit smoking were instructed to reduce the

Because abnormalities in opioid neurotransmission appear to underlie some of the inherited risk f... more Because abnormalities in opioid neurotransmission appear to underlie some of the inherited risk for alcoholism, we examined the effects of naloxone, an opioid antagonist, on corticotropin and cortisol responses in nonalcoholic subjects differentiated by paternal history of alcoholism. Placebo-controlled, balanced, within-subject design involving 2 test days over a period of 3 to 7 days. Thirty-six subjects (67% male; 53% paternal-history-positive; mean age = 25.0 years) were screened to exclude substance abuse or dependence. Subjects received intravenous naloxone 125 microg/kg or placebo, with sessions in random order. Plasma corticotropin and cortisol were measured for up to 120 min post infusion. Corticotropin responses at baseline and following naloxone did not differ by paternal history of alcoholism; however, paternal-history-positive subjects exhibited greater cortisol concentrations at baseline, and at 15 and 30 min after naloxone administration. Paternal-history-positive subjects also had an earlier and greater peak cortisol response to naloxone and a nonsignificant trend for a greater area under the cortisol time curve than paternal-history-negative subjects. These findings suggest that individuals with greater vulnerability to alcoholism may have altered Hypothalamic-pituitary axis (HPA) dynamics, a finding that is consistent with a growing body of data on the role of opioidergic neurotransmission in the inherited risk of alcoholism.

While the pathologies associated with in utero smoke exposure are well established, their underly... more While the pathologies associated with in utero smoke exposure are well established, their underlying molecular mechanisms are incompletely understood. We differentiated human embryonic stem cells in the presence of physiological concentrations of tobacco smoke and nicotine. Using post hoc microarray analysis, quantitative PCR, and immunoblot analysis, we demonstrated that tobacco smoke has lineage-and stage-specific effects on human embryonic stem cell differentiation, through both nicotine-dependent and -independent pathways. We show that three major stem cell pluripotency/differentiation pathways, Notch, canonical Wnt, and transforming growth factor-β, are affected by smoke exposure, and that Nodal signaling through SMAD2 is specifically impacted by effects on Lefty1, Nodal, and FoxH1. These events are associated with upregulation of microRNA-302a, a post-transcriptional silencer of Lefty1. The described studies provide insight into the mechanisms by which tobacco smoke influences fetal development at the cellular level, and identify specific transcriptional, post-transcriptional, and signaling pathways by which this likely occurs.

Smoking during pregnancy is a significant public health concern. Maternal smoking increases the r... more Smoking during pregnancy is a significant public health concern. Maternal smoking increases the risk of spontaneous abortion, low birth weight, premature delivery, sudden infant death syndrome and learning and behavioral problems in the offspring. Unfortunately, the majority of pregnant women do not quit smoking during pregnancy. Although pharmacotherapy may improve smoking cessation rates in pregnancy, very few studies exist that have studied the safety and efficacy of medications to treat pregnant smokers. This article reviews the available safety and efficacy data for the use in pregnancy of the five first-line therapies and two second-line therapies that are recommended for smoking cessation in non-pregnant smokers. Other promising nicotine replacement therapies are also reviewed. Ultimately, the choice whether to use pharmacotherapy for smoking cessation should be made jointly by the pregnant smoker and her health care provider. This article reviews factors that may be considered when prescribing pharmacotherapy to pregnant smokers (i.e. the role of behavioral counseling, identification of appropriate patients, potential advantages and disadvantages of each of the pharmacotherapies, proposed monitoring strategies, dose and duration and goals of treatment). More research regarding the safety and efficacy of pharmacotherapy during pregnancy is needed to define the risk/benefit profile of each medication for use in smoking cessation in pregnant women. [Oncken CA, Kranzler HR. Pharmacotherapies to enhance smoking cessation during pregnancy. Drug Alcohol Rev 2003;22:191 -202]

Nicotine & Tobacco Research, 2006

To date, we have no valid biomarkers that serve as proxies for tobacco-related disease to test po... more To date, we have no valid biomarkers that serve as proxies for tobacco-related disease to test potential reduced exposure products. This paper represents the deliberations of four workgroups that focused on four tobacco-related heath outcomes: Cancer, nonmalignant pulmonary disease, cardiovascular disease, and fetal toxicity. The goal of these workgroups was to identify biomarkers that offer some promise as measures of

Psychiatric Clinics of North America, 1999

Journal of Maternal-fetal & Neonatal Medicine, 2009

Objective-To examine the short-term effects of the nicotine patch or nasal spray on measures of n... more Objective-To examine the short-term effects of the nicotine patch or nasal spray on measures of nicotine exposure, withdrawal symptoms, and on maternal and fetal heart rates in pregnant smokers.

Obstetrical & Gynecological Survey, 1997

To compare blood concentrations of nicotine and cotinine and maternal and fetal hemodynamic effec... more To compare blood concentrations of nicotine and cotinine and maternal and fetal hemodynamic effects resulting from use of nicotine gum versus cigarette smoking in pregnant smokers. Pregnant women (24 to 36 weeks&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; gestation) who smoked chronically were randomly assigned with a 1:2 randomization scheme to either a group that smoked cigarettes (n = 10) or to a group that stopped smoking and chewed at least six pieces of nicotine gum (2 mg nicotine per piece) per day (n = 19). Blood nicotine and cotinine concentrations, maternal heart rate and blood pressure, uterine resistance index, and fetal heart rate and umbilical artery resistance index were obtained before and after one cigarette was smoked at baseline and after 5 continuous days of either chewing gum or smoking. A significant reduction from baseline in nicotine (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) and cotinine (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0025) concentrations was observed in those who chewed nicotine gum compared with those who smoked cigarettes. No significant differences in the changes in maternal or fetal hemodynamic parameters from baseline to estimated time of peak nicotine exposure were observed between those who smoked cigarettes and those who chewed nicotine gum. Short-term use of nicotine gum delivers less nicotine than usual cigarette smoking in pregnant women.

Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2015

Electronic cigarettes (e-cigarettes) represent an emerging public health issue. These devices del... more Electronic cigarettes (e-cigarettes) represent an emerging public health issue. These devices deliver nicotine along with other constituents, including flavorants, via an inhalable aerosol. Their uptake is rapidly increasing in both adults and youths, primarily among current smokers. Public debate is increasing on how these devices should be regulated and used, yet only limited peer-reviewed research exists. To develop a informed policy for e-cigarettes, their effects on human behavior, physiology, and health need to be understood. This paper describes proceedings from a National Institutes of Health-sponsored workshop, which was held in November 2013, to identify research needs related to the effects of e-cigarettes. Discussion topics included e-cigarette risks and abuse potential; the potential role for e-cigarettes in harm reduction and smoking cessation; unintended consequences of e-cigarette use, such as becoming a gateway to conventional cigarettes; and dual use of both e-ciga...

Tobacco Control, 2000

Background In the USA, of the four million women who deliver babies each year, approximately 0.8–... more Background In the USA, of the four million women who deliver babies each year, approximately 0.8–1 million smoke during their pregnancies. Smoking has a substantial adverse impact on pregnancy outcomes including growth retardation, preterm birth, ...

Thorax, 2008

Background: Varenicline, a new treatment for smoking cessation, has demonstrated significantly gr... more Background: Varenicline, a new treatment for smoking cessation, has demonstrated significantly greater efficacy over placebo and sustained release bupropion (bupropion SR). A study was undertaken to compare a 12-week standard regimen of varenicline with a 10

Psychopharmacology, 2001

Rationale: Naltrexone treatment of alcohol dependence is associated with adverse events that may ... more Rationale: Naltrexone treatment of alcohol dependence is associated with adverse events that may limit its effectiveness. Consequently, understanding the impact of adverse events on medication compliance and treatment retention may enhance naltrexone therapy of alcoholism. Objectives: To examine the relations among adverse events, drinking behavior, medication compliance and study retention in alcoholics receiving naltrexone for relapse prevention. Methods: The current report is based on analysis of data from 92 subjects who participated in two previously published studies. Moderate or severe adverse effects were monitored weekly and categorized as either neuropsychiatric (NP) or gastrointestinal (GI). Medication compliance was determined by weekly urinary riboflavin testing. Study retention was determined by the proportion of study weeks completed by the subject. The causal relations among adverse events, medication compliance and study retention were analyzed separately for NP and GI adverse events using regression-based recursive path models. Results: Both the NP and GI models fit the data well [NP model: χ 2 (4)=0.59, P=0.96; GI model: χ 2 (4)=2.81, P=0.59]. NP adverse events exerted little influence on medication compliance (β=-0.17, P=0.071), but directly decreased the length of study retention (β=-0.35, P<0.001). In contrast, there was a significant impact of GI adverse events on medication compliance (β=-0.29, P=0.002), but not directly on study retention (β=-0.14, P=0.081). Conclusion: Future studies aimed at enhancing the effectiveness of naltrexone should examine ways of reducing both NP and GI adverse events, in order to enhance both medication compliance and treatment retention.

Pharmacology Biochemistry and Behavior, 1997

of cotinine in humans: physiologic, subjective, and cognitive effects. PHARMACOL BIOCHEM BEHAV 57... more of cotinine in humans: physiologic, subjective, and cognitive effects. PHARMACOL BIOCHEM BEHAV 57(4) [643][644][645][646][647][648][649][650] 1997.-Preliminary data suggest that cotinine, the major metabolite of nicotine, may be behaviorally active. Studies involving the administration of cotinine at doses that produce high blood concentrations (in excess of those produced by cigarette smoking) may be of interest. This inpatient, 10-day human study examined the safety and the effects from several high doses of oral cotinine fumarate (40, 80, or 160 mg) or placebo in abstinent cigarette smokers. All subjects smoked cigarettes ad lib during the first 2 days of the study, then were required to be abstinent beginning on the third day. All subjects were given placebo on this day to wash out nicotine before the administration of cotinine. Subjects were subsequently randomly assigned in a doubleblind manner to cotinine or placebo for the next 3 days to determine the safety profile of cotinine. All subjects were given placebo on the final 3 days to examine cotinine withdrawal symptoms. The results showed no significant physiologic, subjective, or performance effects across the various doses of cotinine and placebo. Furthermore, no cotinine withdrawal effects were observed. This study demonstrates that short-term administration of cotinine to humans at levels as high as 10 times that attained from cigarette smoking is safe with no observable acute or withdrawal effects from cotinine in this setting. © 1997

Pediatric Research, 2008

Maternal smoking doubles the risk of delivering a low birth weight infant.

Pediatric Research, 2003

The aim of this study was to compare catecholamine concentrations in the fetal umbilical artery c... more The aim of this study was to compare catecholamine concentrations in the fetal umbilical artery cord blood from the offspring of smokers versus the offspring of nonsmokers. Pregnant women who were self-identified as smokers (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;/=10 cigarettes per day throughout pregnancy) or nonsmokers were recruited for study participation. Maternal blood was collected for cotinine concentrations. Umbilical artery cord blood was collected at delivery for arterial pH and catecholamine concentrations. Cord blood was obtained from 51 subjects, including 21 smokers and 30 nonsmokers. Median epinephrine concentrations [304 pg/mL versus 597 pg/mL (Mann-Whitney U = 170; p = 0.006)] and median norepinephrine concentrations [3148 pg/mL versus 6558 pg/mL (Mann-Whitney U = 191; p = 0.006)] were significantly lower in smokers compared with nonsmokers, respectively. After controlling for gestational age, route of delivery, and arterial pH, log-transformed epinephrine concentrations between smokers and nonsmokers were statistically significant (p = 0.03), with a similar trend for log-transformed norepinephrine concentrations (p = 0.07). Analyses of the data using cotinine &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;20 ng/mL to classify nonsmokers also showed differences in epinephrine concentrations between groups (p = 0.02). These results are consistent with results from animal studies showing that catecholamine concentrations may be affected by prenatal nicotine exposure. Further studies are needed to validate these findings and to examine the specific mechanism by which these differences may arise.

Patient Education and Counseling, 2006

Objective: Rates of cigarette smoking are higher among women who receive obstetric care through p... more Objective: Rates of cigarette smoking are higher among women who receive obstetric care through publicly funded prenatal clinics. This study compared smoking outcomes for pregnant women (n = 105) who were randomized to receive either usual care (standard cessation advice from the health care provider) or an intervention conducted in the prenatal clinic consisting of 1.5 h of counseling plus telephone follow-up delivered by a masters prepared mental health counselor. Methods: Subjects were 105 low income, predominantly Hispanic, pregnant patients in an urban prenatal clinic. Smoking outcomes were assessed at end of pregnancy and 6 months post-partum. Results: At follow-up, 28.3% and 9.4% of participants in the experimental intervention and 9.6% and 3.8% of patients in usual care were abstinent at end of pregnancy ( p = .015) and 6 months post-partum, respectively ( p = .251). Cost of the intervention was 56perpatientandcosttoproduceanon−smokeratendofpregnancywas56 per patient and cost to produce a non-smoker at end of pregnancy was 56perpatientandcosttoproduceanon−smokeratendofpregnancywas299. Conclusions: This model for intervention was cost-effective and was associated with significantly lower smoking rates at end of pregnancy. Practical implications: If these findings are replicated, prenatal clinics could offer the option for intensive smoking cessation treatment by training mental health counselors to deliver one extended smoking cessation counseling session. #

Obstetrics & Gynecology, 1997

Obstetrics & Gynecology, 2002

To evaluate the effect of repeated cigarette smoking on fetal heart rate (FHR) characteristics. F... more To evaluate the effect of repeated cigarette smoking on fetal heart rate (FHR) characteristics. Fifteen chronic smokers who were between 28 and 36 weeks&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; gestation were evaluated during an 8-hour smoking session. Baseline FHR and reactivity were evaluated before an initial cigarette and 4 hours later (after the fourth cigarette), when the effects of smoking on FHR were expected to be maximal. Plasma nicotine was measured at baseline and repeated at times of fetal monitoring. Subjects smoked a mean +/- standard deviation of 22 +/- 6 cigarettes per day. They abstained from smoking for 9.2 +/- 3.2 hours before evaluation. The initial baseline FHR was 134 +/- 9 beats per minute versus 135 +/- 11 beats per minute after the fourth cigarette (P =.17). Plasma nicotine increased from 2.6 +/- 5.6 ng/mL to 24 +/- 9.9 ng/mL after the fourth cigarette (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.001). The initial nonstress test was reactive in 12 of 15 (80%) of the fetuses. After the fourth cigarette, only four of 15 (27%) of the nonstress tests were reactive. A majority of tracings (eight of 15) were initially reactive before smoking and became nonreactive after smoking. Some tracings remained nonreactive (three of 15), and some tracings remained reactive (four of 15) at both assessments. None of the tracings that were initially nonreactive became reactive. The change in reactivity was significant (P =.013). Acute, repeated smoking decreases FHR reactivity.

Nicotine & Tobacco Research, 2014

Topiramate (TOP) blocks glutamate receptors and facilitates GABA (γ-aminobutyric acid) neurotrans... more Topiramate (TOP) blocks glutamate receptors and facilitates GABA (γ-aminobutyric acid) neurotransmission, effects that may facilitate smoking cessation. We compared the effects of behavioral counseling combined with (a) TOP, (b) TOP/nicotine patch (TOP/NIC), or (c) placebo (PLC) for smoking cessation. We conducted a 10-week randomized trial in which subjects and research personnel were blinded to TOP versus PLC but not to the TOP/NIC patch condition. In groups receiving TOP, the medication dosage was titrated gradually up to 200 mg/day. The smoking quit date (QD) was scheduled after 2 weeks of medication treatment. NIC (21 mg) was started on the QD in subjects randomized to the TOP/NIC condition. The main outcome measure was the end-of-treatment, 4-week continuous abstinence rate (CAR; biochemically confirmed). Fifty-seven subjects were randomized to treatment. The 4-week CAR was 1 of 19 (5%) in the PLC group, 5 of 19 (26%) in the TOP group, and 7 of 19 (37%) in the TOP/NIC group (p = .056). Pairwise comparisons showed a difference between TOP/NIC and PLC (p = .042) and a nonsignificant difference between TOP and PLC (p = .18). The PLC group gained 0.37 lb/week, the TOP group lost 0.41 lb/week, and the TOP/NIC group lost 0.07 lb/week (p = .004). Pairwise comparisons showed a difference between TOP and PLC (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001) and between TOP/NIC and PLC groups (p = .035). Paresthesia was more frequent in subjects on TOP than PLC (p = .011). TOP, alone or in combination with the NIC, resulted in a numerically higher quit rate than PLC and decreased weight. A larger, PLC-controlled trial is needed to confirm these findings.