B-mode-guided vector-A-mode versus A-mode biometry to determine axial length and intraocular lens power

Studies of nicotine replacement by 2 mg nicotine polacrilex gum (NG) have typically found that one half to one third of plasma nicotine in recent smokers is replaced. This 5-year study sought to find the extent of nicotine replacement among ex-smokers in the longer term and to identify a mechanism for this relationship. The sample was the special intervention group (N = 3923) in the Lung Health Study, a controlled clinical trial involving smoking cessation. The extent of nicotine replacement was assessed by levels of salivary cotinine. Cotinine levels of ex-smokers using NG after 1 year (219 +/- 149 ng/ml) were similar to those in continuing smokers (290 +/- 159 ng/ml). After 5 years, cotinine levels were the same for NG-using ex-smokers (316 +/- 276 ng/ml), NG-using smokers (309 +/- 240 ng/ml), and NG-non-using smokers (311 +/- 198 ng/ml). Salivary cotinine among NG users at 1 year was only weakly correlated with baseline cotinine levels prior to smoking cessation. Although NG users appear to re-establish cotinine levels characteristic of their smoking, the mechanism by which this occurs remains unclear.     

Blood nicotine and carboxyhemoglobin levels after rapid-smoking aversion therapy.

Studied blood nicotine and carboxyhemoglobin (COHb) levels after rapid smoking in 5 male and 10 female smokers. Male Ss were under 40 yrs of age and females were under 50. Blood nicotine averaged 48.1 ng/mg after rapid smoking compared to 32.4 ng/ml after normal smoking, and COHb levels averaged 12.1% and 8.9%, respectively. Both differences were significant. Normal smoking levels of 92 smokers in other studies averaged around 30 ng/ml nicotine and 8.2–8.5% COHb. There was no evidence that the degree of nicotine and carbon monoxide intoxication produced during raid smoking had any relation to the reduction in the desire to smoke immediately after the session or the decrese in cigarette consumption on the following day. The potential risks of rapid smoking are discussed. It is suggested that these risks might be reduced by using a beta-adrenergic blocker and that the procedure could be made completely safe, possibly without loss of treatment effect, if Ss were instructed not to inhale. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Clinical status of ulcerative colitis in patients who smoke

OBJECTIVES: Ulcerative colitis (UC) is largely a disease of nonsmokers. There are few patients who are current smokers, but we have identified a group and reviewed their clinical status, disease activity, and nicotine exposure to examine whether they remain well controlled while smoking. METHODS: Fifty-one patients from three centers with verified UC were reviewed. RESULTS: Thirty of the group were men; mean age 50 yr, with a mean age of onset of 37 yr. Twenty-two patients had proctosigmoid disease, 12 involvement of left colon, and 17 total colitis. All were current smokers; 41 were cigarette smokers averaging 17 daily. At the onset of colitis 30 were nonsmokers, 25 of them were ex-smokers and 19 developed colitis within 2 yr of stopping smoking. Twenty-eight believed smoking improved disease activity and none felt smoking had a detrimental effect on their UC. Eleven were receiving no medication for UC, 40 were receiving 5-ASA (5-aminosalicylic acid) preparations, and only two took oral steroids. All were in clinical remission, with the exception of one patient; mean St. Marks score was 1.5, out of a possible total of 22. Sigmoidoscopic grades were inactive in all patients except three. Histological assessment showed significant activity in only five. Median serum nicotine was 8 ng/ml (range, 0.4-24.4), median serum cotinine 180 ng/ml (range, 20-453), with corresponding salivary cotinine of 255 ng/ml (range, 34-683). Median rise in nicotine 2 min after a cigarette in 35 patients was 12.1 ng/ml (range, 0.4-44). CONCLUSIONS: Because most current smokers with UC have inactive disease, smoking may contribute to the clinical remission in these patients.     

The influence of smoking and of oral and transdermal nicotine on blood pressure, and haematology and coagulation indices

Nicotine is helpful in stopping smoking but its influence on cardiovascular risk factors is incomplete. Our aim was to determine its effect on blood pressure, routine haematology indices, and coagulation indices relevant to thrombosis. Eighteen subjects were seen whilst smoking (cotinine levels 1119 +/- 414 ng/ml), again after stopping smoking but while using nicotine chewing gum and/or skin patches (392 +/- 198 ng/ml), and again when not using nicotine (cotinine undetectable). There were no significant changes in blood pressures, platelet count, mean platelet volume, viscosity or anti-thrombin III. However, white blood cell count (p = 0.003), lymphocyte count (p = 0.016), red blood cell count (p = 0.02), haemoglobin (p <0.001), fibrinogen (p <0.001) and von Willebrand factor (p = 0.001) all fell between the first and second samples (when still using nicotine) but not between the second and third samples (when off nicotine). Oral and/or transdermal nicotine does not influence blood pressure or the haematology and coagulation indices we have measured.     

Compensatory nicotine self-administration in rats during reduced access to nicotine: An animal model of smoking reduction.

The ability of smoking reduction (e.g., decreasing cigarettes per day) to produce significant reductions in toxin exposure is limited by compensatory increases in smoking behavior. Characterizing factors contributing to the marked individual variability in compensation may be useful for understanding this phenomenon. The goal of the current study was to develop an animal model of smoking reduction and to begin to examine potential behavioral and pharmacokinetic contributors to compensation. Rats trained for nicotine self-administration (NSA) in unlimited access sessions were exposed to a progressive decrease in duration of access to nicotine from 23-hr/day to 10-, 6-, and 2-hr/day. Following a return to 23 hr/day access and extinction, single-dose nicotine pharmacokinetic parameters were determined. Rats exhibited a reduction in total daily nicotine intake during reduced access to NSA, but decreases in nicotine intake were not proportional to decreases in access duration. Compensatory increases in hourly infusion rate were also observed when access was decreased. The magnitude of compensation differed considerably among animals. Early session infusion rate during baseline was significantly correlated, while nicotine clearance was moderately correlated, with 1 measure of compensation. Infusion rates were transiently increased compared to prereduction levels when unlimited access was restored, and this effect was greatest in animals that had exhibited the greatest levels of compensation. These findings indicate that rats exhibit compensatory increases in NSA during reduced access to nicotine, with substantial individual variability. This model may be useful for characterizing underlying factors and potential consequences of compensatory smoking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Physiologic effects of maternal smoking on breast-feeding infants

Women who smoke and breast-feed pose an unknown threat to their infants' health. In this pilot study, relationships between ingestion of nicotine in breast milk and physiologic effects in the infant were investigated. Infant physiologic effects measured were temperature, pulse, respiration, systolic blood pressure, and oxygen saturation. Five smoking and five nonsmoking mother-infant pairs were studied. Breast milk was analyzed for nicotine using gas chromatography. Breast milk from smoking mothers contained a mean of 33.1 ng/mL of nicotine while the breast milk from nonsmoking mothers contained a mean of less than 6.45 ng/mL of nicotine. Infant physiologic measures were taken before and 20 min after breast-feeding. After breast-feeding, infants of smoking mothers had a significant change in respirations and oxygen saturation while infants of nonsmoking mothers had a significant change in pulse only. Results provide a scientific basis for counseling smoking, breast-feeding mothers.     

Transplacental transfer and biotransformation studies of nicotine in the human placental cotyledon perfused in vitro

Our objective was to study the characteristics of transfer and biotransformation of nicotine in the human term placenta. Nicotine transfer was studied by dually perfusing an isolated cotyledon of the human placenta in vitro. Nicotine metabolism to cotinine was investigated in intact tissue during perfusion and in placental microsomal fractions. Following the addition of nicotine (40 ng/ml) to the maternal side of the placenta, distribution into placental tissue (0.43 +/- 0.13 ng/ml/min) was three times higher than transfer to the fetal side of the placenta (0.15 +/- 0.01 ng/ml/min). The steady-state maternal-to-fetal transfer of nicotine was approximately 90% that of antipyrine (a marker of flow-dependent transfer). There was no evidence of nicotine metabolism to cotinine by intact placental tissue or in microsomal fractions. The observation that nicotine readily crosses the human placenta with no evidence of metabolism suggests that nicotine has the potential to cause adverse affects on the developing fetus.     

Changes of smoking habits and cough in men smoking cigarettes with 30% NSM tobacco substitute

The effects of smoking cigarettes with 30% of the tobacco replaced by NSM tobacco substitute, which lowered their tar and nicotine delivery, were studied by comparing them with the effects of conventional cigarettes in a controlled crossover trial lasting 20 months. Chest symptoms, cigarette consumption, and forced expiratory volume in one second (FEV1) were measured each month. Two-hundred men began the trial and 159 completed it. The test cigarettes were acceptable to all but one of the men. In a subsample of 35 men estimates of nicotine intake were obtained from monthly analyses of cigarette stubs. On changing from NSM to control cigarettes six of the 17 men, who were accustomed to low nicotine, kept their nicotine intake down by some change in smoking habit. Before the crossover and this change in smoking habit the men smoking NSM cigarettes had a small but significant reduction of cough. Cigarettes containing 30% NSM and delivering only 1 mg of nicotine are likely to be acceptable to smokers and may reduce coughing. Further trials are needed to confirm these findings and establish what long-term effects such cigarettes may have on smokers' health.     

Effects of Transdermal Nicotine During Imaginal Exposure to Anxiety and Smoking Cues in College Smokers.

In a 2 (patch) × 2 (smoking) × 2 (anxiety) mixed design, 52 undergraduate smokers randomly received a nicotine (21 mg) or placebo patch. After a 4-hr nicotine absorption/deprivation period, participants imagined several scenarios varying in cue content: (a) anxiety plus smoking, (b) anxiety, (c) smoking, and (d) neutral. Although smoking urge increased in both the nicotine and placebo conditions after the absorption/deprivation period, those who received the placebo reported significantly greater urge. During the cue reactivity trials, a significant Patch × Smoking × Anxiety interaction effect was observed for urge. However, participants who received nicotine still experienced moderate urges, indicating that nicotine did not attenuate cue-elicited urge. Transdermal nicotine did not diminish anxiety during the absorption/deprivation period or in response to the cues. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ever Users Versus Never Users of a "Less Risky" Cigarette.

The authors surveyed 173 smokers who purchased and 114 smokers who knew about but did not purchase Eclipse--a tobacco industry product that is advertised as a reduced risk cigarette. Most low-tar/nicotine cigarette users who purchased Eclipse believed Eclipse was safer than low-tar/nicotine cigarettes both for their own health (73%) and for the health of others around them (86%). Additionally, many viewed Eclipse as a step toward quitting (53%). The authors did not identify robust predictors of Eclipse use. At 6 months follow-up, Eclipse users were as likely to have tried to quit as nonusers; however, the small sample size does not rule out the possibility that Eclipse use undermines quit attempts. The authors conclude that almost all users believe Eclipse is safer than low-tar cigarettes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reducing craving for cigarettes while decreasing smoke intake using capsaicin-enhanced low tar cigarettes.

The effects on smoking behavior and subjective evaluation of adding capsaicin (a pungent principle of chili pepper) to a low tar and nicotine cigarette were studied in 12 cigarette smokers. In a 4-hr session, Ss inhaled smoke from 3 types of cigarettes: low tar and nicotine with capsaicin added; low tar and nicotine without capsaicin (control); and commercial high tar and nicotine. Ss puffed significantly less on the capsaicin cigarettes than on the other 2 types of cigarettes and reported greater reduction in cigarette craving after smoking capsaicin cigarettes than after smoking control low nicotine cigarettes. Estimated nicotine intake and respiratory tract sensations for the capsaicin cigarettes were also significantly higher than for the control cigarettes. Results support the view that respiratory tract sensations are important in reducing smokers' craving for cigarettes and in modulating smoking behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Oncogenic ras induces gastrin gene expression in colon cancer

BACKGROUND: Exposure to environmental tobacco smoke is associated with detrimental effects on pulmonary function in children. The authors investigated the relation between airway complications in children receiving general anesthesia and the passive inhalation of tobacco smoke. METHODS: Six hundred two children scheduled to receive general anesthesia were enrolled in this prospective study. The anesthesiologist and the recovery room nurse, unaware of the smoke exposure history, recorded the occurrence of airway complications. A history of passive smoking was assessed by measuring the urinary concentration of the major nicotine metabolite cotinine and by questionnaire. RESULTS: Airway complications occurred in 42% of the patients with urinary concentrations of cotinine > or =40 ng/ml, in 33% of the patients with concentrations of cotinine between 10.0 and 39.9 ng/ml, and in 24% of the patients with concentrations of cotinine < 10 ng/ml (P = 0.01 for the trend among the three groups). The gender of the child (P = 0.001) and the educational level of the child's mother (P = 0.0008) significantly modified the effect of the concentration of cotinine on the incidence of adverse respiratory events. CONCLUSIONS: There is a strong association between passive inhalation of tobacco smoke and airway complications in children receiving general anesthesia. The relationship is greatest for girls and for those whose mothers have a lower level of education. Passive smoking should be regarded as a risk factor in children undergoing general anesthesia.     

Chronic nicotine intake causes vascular dysregulation in the rat gastric mucosa

Chronic cigarette smoking has adverse effects on peptic ulcer disease because the healing of ulcers is delayed and the incidence of relapses is enhanced. Short term intake of nicotine induces vascular damage in the rat gastric mucosa, but the pathophysiological mechanisms of nicotine's action in the stomach are largely unknown. In this study rats were treated with nicotine, added to their drinking water, for 50 days. They were then anaesthetised and their stomachs perfused with acidified acetylsalicylic acid (ASA). Chronic nicotine treatment failed to change the effects of acidified ASA to induce gastric mucosal acid back diffusion, haemorrhagic damage and bleeding. Basal blood flow in the gastric mucosa was also unchanged by chronic nicotine intake, whereas the mucosal hyperaemia evoked by ASA induced acid back diffusion was averted. The concentrations of sulfidoleukotrienes were significantly augmented in the gastric wall of nicotine treated rats. These data show that chronic nicotine intake causes dysregulation of the gastric microcirculation, an effect that is associated with biochemical changes in the stomach. This study thus substantiates the adverse effects of smoking on gastric mucosal pathophysiology. These data suggest that inappropriate regulation of gastric mucosal blood flow inhibits recovery from gastric mucosal injury in smokers.     

Pre-mRNA processing enhancer (PPE) element increases the expression of an intronless thymidylate synthase gene but does not affect intron-dependent S phase regulation

Maternal smoking during pregnancy causes reduction of fetal breathing movements, an effect attributed to nicotine in fetal blood. Nicotine is metabolized to cotinine which has a long plasma half-life and exhibits slow clearance across membrane barriers. It is also known to activate placental phospholipase-A2-like enzymes, resulting in formation of prostaglandins. Therefore, we studied transport of nicotine in isolated perfused cotyledon of normal human term placenta. The placental cotyledon was perfused with aerated (21% O2, 5% CO2) Krebs-Ringer bicarbonate buffer (pH 7.4, 37 degrees C) containing 2% albumin on both maternal (230 ml, 15 ml/min, 35 mm Hg) and fetal (93 ml, 1.75 ml/min, 70 mm Hg) sides in a closed recirculating system. Nicotine (2 mg) was added to the maternal perfusate; perfusate samples (1 ml) were collected from both sides at regular intervals and analyzed for nicotine and cotinine by high-pressure liquid chromatography. This study gave the following results: (1) In about 60-80 min, 18.6% of the nicotine added to the maternal perfusate was transferred to the fetal perfusate, and the maternal/fetal concentration ratio reached 1.0. These results show rapid placental transfer of nicotine, consistent with its high lipid solubility. (2) Less than 1% is metabolized to cotinine in placenta. The ratio of cotinine concentrations in maternal and fetal perfusates reached 1.0 in about 40 min. These studies were also verified using 14C-nicotine. (3) Maximal reduction in fetal breathing movements occurs at about 30 min, and recovery occurs at 90 min after tobacco smoking by the mother. These observations agree with the rate of placental transfer of nicotine. (4) When nicotine was added on the fetal side, part of it was metabolized to cotinine. However, the maximal concentration of cotinine was twice higher on fetal than on maternal side. These observations suggest that accumulation of cotinine on fetal side may activate prostaglandin formation and trigger spontaneous abortions in pregnant smokers.     

Ventilation during simulated altitude, normobaric hypoxia and normoxic hypobaria

Maternal smoking increases the risk of the sudden infant death syndrome (SIDS) 2-4-fold. The mechanism is unknown but may be related to hypoxia responses. Recovery from hypoxic apnea by young mammals depends on gasping and bradycardia. We asked whether prenatal nicotine exposure, reported to reduce hypoxic survival in 2 day old rat pups, acted by impairing gasping or bradycardia. Pregnant rats were infused throughout gestation and 1 week postnatally with nicotine tartrate (NIC) 12 mg/kg per day or saline (CON). Maternal plasma nicotine was 134.4 +/- 42 ng/ml, significantly reducing pup body weight. Pups at 3-28 days were exposed to anoxia (97% N2/3% CO2) until gasping ceased, while breathing and heart rate were recorded. NIC and CON groups were not significantly different at any age, in baseline heart rate, respiratory rate, the time course for bradycardia, time to gasp onset, duration of gasping, or number of gasps, although most of these variables declined significantly with age. We conclude that responses to anoxia are not affected by prenatal high-dose nicotine.     

Human immunodeficiency virus and resistance]

CONTEXT: Racial differences in tobacco-related diseases are not fully explained by cigarette-smoking behavior. Despite smoking fewer cigarettes per day, blacks have higher levels of serum cotinine, the proximate metabolite of nicotine. OBJECTIVE: To compare the rates of metabolism and the daily intake of nicotine in black smokers and white smokers. DESIGN: Participants received simultaneous infusions of deuterium-labeled nicotine and cotinine. Urine was collected for determination of total clearance of nicotine and cotinine, fractional conversion of nicotine to cotinine, and cotinine elimination rate. Using cotinine levels during ad libitum smoking and clearance data, the daily intake of nicotine from smoking was estimated. SETTING: Metabolic ward of a university-affiliated public hospital. PARTICIPANTS: A total of 40 black and 39 white smokers, average consumption of 14 and 14.7 cigarettes per day, respectively, of similar age (mean, 32.5 and 32.3 years, respectively) and body weight (mean, 73.3 and 68.8 kg, respectively). MAIN OUTCOME MEASURES: Clearance (renal and nonrenal), half-life, and volume of distribution of nicotine and cotinine and the calculated daily intake of nicotine. RESULTS: The total and nonrenal clearances of nicotine were not significantly different, respectively, in blacks (17.7 and 17.2 mL x min(-1) x kg(-1)) compared with whites (19.6 and 18.9 mL x min(-1) x kg(-1)) (P=.11 and .20). However, the total and nonrenal clearances of cotinine were significantly lower, respectively, in blacks (0.56 and 0.47 mL x min(-1) x kg(-1)) than in whites (0.68 vs 0.61 mL x min(-1) x kg(-1); P=.009 for each comparison). The nicotine intake per cigarette was 30% greater in blacks compared with whites (1.41 vs 1.09 mg per cigarette, respectively; P=.02). Volume of distribution did not differ for the 2 groups, but cotinine half-life was higher in blacks than in whites (1064 vs 950 minutes, respectively; P = .07). CONCLUSIONS: Higher levels of cotinine per cigarette smoked by blacks compared with whites can be explained by both slower clearance of cotinine and higher intake of nicotine per cigarette in blacks. Greater nicotine and therefore greater tobacco smoke intake per cigarette could, in part, explain some of the ethnic differences in smoking-related disease risks.     

The influence of caffeine on nicotine's discriminative stimulus, subjective, and reinforcing effects.

Caffeine may acutely alter the discriminative stimulus and subjective effects of nicotine, perhaps explaining the association of coffee intake with smoking status. In this study, smokers were initially trained to discriminate 20 μg/kg nicotine by nasal spray from placebo (0). Then, generalization of nicotine discrimination was tested, using both 2- and 3-choice ("novel" option) procedures, across a range of doses (0-20 μg/kg) following pretreatment with 0, 2.5, and 5.0 mg/kg caffeine p.o. Nicotine reinforcement was assessed after the end of generalization testing using a choice procedure. Caffeine pretreatment did not alter nicotine discrimination and self-administration. Caffeine and nicotine influenced some subjective and cardiovascular responses, but there were no interaction effects except for diastolic blood pressure. These results do not support the notion that caffeine acutely alters nicotine's discriminative stimulus, subjective, or reinforcing effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dose released and absolute bioavailability of nicotine from a nicotine vapor inhaler

In an open, randomized, three-way crossover study, 14 healthy smokers used one type of nicotine vapor inhaler intensely for 20 minutes every hour for 11 hours (12 administrations). Two different inhalation techniques were applied, shallow frequent sucking (buccal mode) and deep inhalations (pulmonary mode). The determination of nicotine was performed by capillary gas chromatography after single-step liquid-liquid extraction of the plasma sample. Nicotine was detected by means of a nitrogen-sensitive detector, giving high selectivity and sensitivity. The mean (+/- SD) nicotine dose released from each nicotine vapor inhaler unit was estimated at 4.00 +/- 0.60 mg (buccal mode) and 3.87 +/- 0.75 mg (pulmonary mode), inhaled with approximately 15 L of air. Mean (+/- SD) peak plasma level of the last dosing interval was 32.0 +/- 8.7 ng/ml and 34.2 +/- 8.9 ng/ml for the buccal and the pulmonary technique, respectively, achieved after 0.33 and 0.50 (median) hour, respectively. The mean (95% confidence interval [CI]) absolute bioavailability of nicotine was 51 (95% CI, 40 to 65) and 56 (95% CI, 47 to 67) when the buccal and pulmonary techniques were used, respectively. A significant correlation was found between systemically available dose and average steady-state nicotine plasma concentration. Based on the achievement of similar nicotine plasma levels, it may be concluded that the two modes of inhalation appear to be clinically equivalent.