Group Of Heavy Smokers Research Articles

S.10.05 Pharmacological treatment of pathological gambling

Behavioral addictions like pathological gambling share many clinical characteristics with substance dependence. In addition, both types of disorders are associated with impairments in inhibitory control. Studies in patients with substance use disorders point to hyporesponsiveness of the dorsomedial prefrontal cortex. However, no such data exist on behavioral addictions.Using functional magnetic resonance imaging, we investigated the neural circuitry associated with impaired response inhibition in a group of male problem gamblers (n = 17) using a stop signal task. We included control conditions tailored to specifically isolate neural correlates of inhibitory control. To investigate the specificity of effects, a group of heavy smokers (n = 18) and a group of healthy controls (n = 17) were also included.Groups did not differ in behavioral performance on the stop signal task. However, both problem gamblers and heavy smokers showed hyporesponsiveness of the dorsomedial prefrontal cortex compared to healthy controls, during successful as well as failed response inhibition. These effects were robust against adjustments for depression and adult attention deficit scores.These findings suggest that hypoactivation of the inhibition circuit is a shared neural mechanism in substance use disorders and behavioral addictions. As such, they support the reclassification of pathological gambling as a behavioral addiction in DSM-V.

The role of norharman in alcohol dependence and smoking: The potential inhibitory role of norharman on the urge for alcohol and nicotine use

The aim of this study was to investigate the role of the endogenous substance norharman in processes of alcohol and nicotine or tobacco dependence in both humans and animals. For this purpose heavy smokers and excessive alcohol drinkers were recruited, and rats were made dependent on alcohol and nicotine. Plasma concentrations of norharman were measured in drug‐naïve, drug‐free and drug‐taking situations. In addition, craving and nicotine dependence were measured in the group of heavy smokers, while in the animal studies the effect of exogenously administered norharman on the behavioural signs of alcohol and nicotine withdrawal were determined. Humans who abstained from smoking and drinking for a period of 12 h showed normal plasma levels of norharman. Resumption of smoking, but not drinking, generated elevated plasma levels of norharman, especially after smoking self‐made non‐filter cigarettes. Although craving after a period of abstinence was stronger in smokers with high tobacco dependence compared to those with low dependence, the plasma levels of norharman were only negatively related to craving among low nicotine‐dependent smokers. From the animal experiments it was concluded that nicotine intake had no effect on plasma levels of norharman. On the other hand, withdrawal symptoms elicited in nicotine‐dependent rats could be attenuated by exogenous administration of norharman. Rats made alcohol‐dependent by forced intake of an ethanol‐containing diet showed higher norharman levels in plasma and brain compared to alcohol‐naïve rats. This increase is caused by a lower clearance of norharman by the liver of alcohol‐fed rats. After stopping alcohol intake, behavioural signs of alcohol withdrawal occurred which were inhibited by pretreatment with norharman. The results indicate that norharman is involved in processes of alcohol and tobacco dependence and that this substance may be a candidate adjuvant in alleviating abstinence symptoms.

Evaluation of the relationship between smoking during pregnancy and subgingival microbiota

Numerous studies have shown that smoking negatively affects periodontal health. Hormonal changes, which occur during pregnancy have also been reported to have adverse effects on the periodontal tissues or indirectly through alterations in the subgingival bacterial flora. At present, no knowledge exists concerning possible effects of smoking on the composition of subgingival plaque in pregnancy. The purpose of the present study was to evaluate the effects of smoking during pregnancy on the subgingival plaque bacteria most commonly associated with periodontal disease. A total number of 181 women were examined within 72 h post-partum. Smoking status was recorded by means of a self-reported questionnaire and the study population was divided into three groups; non-smokers, light smokers, and heavy smokers. In each woman, two subgingival plaque samples were obtained from mesio- or disto-buccal aspect of randomly selected one molar and one incisor tooth by sterile paperpoints. Clinical periodontal recordings comprising presence of dental plaque, bleeding on probing (BOP), and probing pocket depth (PPD) were performed at six sites per each tooth at all teeth. Plaque samples were analysed by checkerboard DNA-DNA hybridization with respect to 12 bacterial species. In all analyses, the individual subject was the computational unit. Thus, mean values for all clinical parameters were calculated and bacterial scores from each individual sample were averaged. Statistical methods included chi2 test, Kruskal-Wallis test and Mann-Whitney U-test. Mean ages were similar in the study groups. Plaque, BOP and PPD recordings were lower in the heavy-smoker group, but the differences were not statistically significant (p>0.05). The detection rates and bacterial loads of the specific subgingival bacteria exhibited no significant differences between the groups. No correlation could be found between smoking status and detection rates and bacterial loads of various bacterial species. The present findings suggest that smoking during pregnancy does not have a significant effect on the composition of subgingival plaque bacteria.

Cigarette smoking is related to a decrease in semen volume in a population of fertile men

Cigarette smoking is very common despite worldwide anti-smoking campaigns. It is considered as one of the causes of sub-fertility in males. It may result in decreased sperm concentration, poor motility and morphology, and high rates of sperm with DNA damage. However, even though many studies have shown the association of cigarette smoking with reduced semen quality in men diagnosed with infertility, however, studies evaluating the impact of smoking on the semen quality of normal fertile men are lacking. The goal of our study was to evaluate the semen quality and hormonal levels in mild, moderate, heavy and nonsmokers fertile men undergoing vasectomy for sterilization purposes. Retrospective study at a tertiary care institution. University based center. The Institutional Review Board approved the study and all the patients provided informed consent. 889 vasectomies for voluntary sterilization purposes were performed from January 1999 to March 2003. Computer-assisted semen analysis was performed on all specimens, with a Motion Analysis (VP 50) semen analyzer. We divided the patients into four groups: non-smokers (Group A; n = 522), mild smokers (Group B, < − 10 cigarettes/day; n = 143), moderate smokers (Group C, − 11–20 cigarettes/day; n = 154), and heavy smokers (Group D, > − 20 cigarettes/day; n = 70). We evaluated sperm concentration, motility, motion parameters, and hormonal levels in these men at the time of their visit. Data was evaluated with ANOVA. No differences were seen across Groups A to D in sperm concentration (109.18 ± 76.21, 107.49 ± 86.62, 124.51 ± 87.3, and 118.41 ± 85.21; P = 0.071), motility (60.35 ± 15.67, 59.8 ± 15.79, 60.82 ± 14.42, and 53.9 ± 13.18; P = 0.678), follicle-stimulating hormone (3.67 ± 2.10, 4.021 ± 2.10, 3.40 ± 2.4, and 3.53 ± 1.57; P = 0.562), luteinizing hormone (3.32 ± 1.6, 3.66 ± 4.02, 3.03 ± 1.57, and 2.63 ± 1.17; P = 0.213), and serum total testosterone (558.59 ± 178.4, 595.26 ± 175.33, 561.23 ± 166.62, and 659.92 ± 212.67; P = 0.266). Also, sperm motion characteristics did not differ across the groups: curvilinear velocity (71.99 ± 16.44, 71.008 ± 16.37, 72.81 ± 14.41, and 70.2 ± 13.38; P = 0.828), linear velocity (40.58 ± 10.33, 39.43 ± 10.72, 39.60 ± 9.752, and 38.85 ± 7.50; P = 0.796), linearity (55.72 ± 7.86, 54.82 ± 8.73, 53.4 ± 9.16, and 54.63 ± 8.38; P = 0.211), lateral head displacement (3.03 ± 0.92, 3.1 ± 0.88, 3.28 ± 0.99, and 3.001 ± 0.94; P = 0.473), and beat cross frequency (23.79 ± 6.48, 24.01 ± 4.96, 23.47 ± 7.28, and 21.74 ± 7.96; P = 0.499). Semen volume was the only semen parameter, which tends to decrease according to the number of cigarettes smoked (2.82 ± 1.44, 2.42 ± 1.403, 2.30 ± 1.151, and 2.08 ± 0.82; P = 0.004). Semen volume tends to decrease according to the number of cigarettes smoked. A decrease in semen volume may be the first sign of semen quality impairment in cigarette smokers even before a decline in sperm concentration, percent sperm motility and normal sperm morphology.

Genetic polymorphisms of X-ray repair cross-complementing group 1 (XRCC1) and smoking as a risk factor

Problem: X-ray repair cross-complementing group 1 (XRCC1) is a single DNA break repair protein forming a BER (base-excision repair) complex. A recent case-control study of the head and neck squamous cell carcinoma (HNSCC) reported associations with 2 polymorphisms of the XRCC1 including the exon 6, 194 Arg/Arg genotype and the exon 10, 399 Gln/Gln genotype. Reduced DNA repair capacity has been suggested as a risk factor for HNSCC. Methods: We conducted a case-control study of 103 HNSCC patients and 105 control subjects. Control subjects included patients seen in the same clinic with benign conditions who had undergone treatment with no history of chronic disorder or malignant tumor. A questionnaire collected data on the patient’s history and degree of smoking. The patient’s age, sex, diagnosis, stage, site of origin, and pathologic diagnosis were examined by reviewing the patient’s medical records. XRCC1 polymorphisms were determined using a multiplex PCR/RFLP method. Multivariate logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for each XRCC1 genotype with adjustment for the matching factors (age and sex as well as cigarette smoking) and the following results were obtained. Results: (1) The risk of HNSCC based on the degree of smoking increased to 3.32 (CI; 1.00–11.08) in the light smoking group(<20 pack-years) and definitely increased in the heavy smoking group(<;20 pack-years) to 12.04 (CI; 3.47–41.79) compared to the nonsmoking group. (2) An associative comparison study of smoking and XRCC1 polymorphism revealed that the HNSCC risk increased in the XRCC1 codon 194 Arg/Arg and Trp/Trp genotypes of the smoking group to 7.87 (CI; 1.74–34.88) and 8.13 (CI; 1.40–47.03), respectively compared to the XRCC1 codon 194 Arg/Arg genotype of the nonsmoking group. The HNSCC risk in XRCC1 codon 399 Arg/Gln genotype of the smoking group increased to 3.99 (CI; 1.07–14.92) compared to the Arg/Arg genotype of the nonsmoking group. (3) A comparison study among a laryngeal cancer group and nonlaryngeal cancer group revealed the following results: (a) the risk of HNSCC based on smoking revised by XRCC1 codon 194 and 399 markedly increased to 74.33 (CI; 6.12–902.63) and 56.63 (CI; 5.24–612.19) under a history of heavy smoking (<20 pack-years) in the laryngeal cancer group; (b) the risk of HNSCC based on smoking revised by XRCC1 codon 194 and 399 increased to 6.57 (CI; 1.58–27.36) and 5.41 (CI; 1.39–21.05) under a history of heavy smoking (<20 pack-years) in the nonlaryngeal cancer group. Conclusion: In conclusion the findings of our study reveal that the risk of HNSCC increases based on the degree of smoking and that XRCC1 codon 194 Arg/Trp and Trp/Trp, XRCC1 codon 399 Arg/Gln and Gln/Gln are risk factors that increase the development of HNSCC. Significance: Therefore, to prevent HNSCC, it is very important to abstain from smoking. It is also assumed that the XRCC1 polymorphism can be a useful marker for the prevention and development of HNSCC. Support: None reported.

Heavy smokers: a qualitative analysis of attitudes and beliefs concerning cessation and continued smoking.

In this qualitative analysis, we conducted intensive interviews of a group of heavy smokers to better understand psychosocial characteristics related to smoking and quitting. A total of 51 heavy smokers were recruited to participate in this study. In-depth interviews lasting 60-90 min explored factors related to smoking and attitudes toward cessation. N'Vivo was used to analyze the data. We modeled a number of factors related to heavy smoking in this population. A comprehensive model appeared to fit the data well. Key factors related to heavy smoking included those that promote smoking, those that influence quitting, perceptions of quitting, and explanations of failure. Along each of these dimensions, clusters of variables, such as the social environment, emotional identity, addiction, and physical health, emerged as being important in understanding the perceptions of heavy smokers when it comes to smoking and quitting. The models add important information to our understanding of heavy smokers. This work indicates that this sample of heavy smokers had many issues around smoking and quitting, including the perceived difficulty of quitting, physical and psychological addictions to smoke, reinforcement for smoking, and a tendency to procrastinate in quitting.

Effect of a standardized grape seed extract on low-density lipoprotein susceptibility to oxidation in heavy smokers

The aim of our study was to evaluate the effect of a standardized formulation of a polyphenolic extract of grapes (Leucoselect-Phytosome [LP]) on low-density lipoprotein (LDL) susceptibility to oxidation in a group of heavy smokers. A randomized, double-blind, crossover study was undertaken in 24 healthy male heavy smokers, aged ≥ 50 years. Enrolled subjects were given 2 capsules twice daily for 4 weeks (phase 1). Each capsule contained 75 mg of a grape procyanidin extracts and soy-phosphatidlcholine or placebo consisiting of 75 mg lactose and soy-phosphatidlcholine. A wash out period of 3 weeks was then followed by 4 weeks of the opposite treatment (phase 2). Blood samples were taken at baseline and at the end of each phase and assayed for plasma lipids and LDL susceptibility to oxidation. Compliance was good, and no adverse effects were recorded. Subjects did not show significant modification of total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C) and LDL-C during LP treatment. Among oxidative indices, thiobarbituric acid reactive substances (TBARS) concentration was significantly reduced in subjects taking LP (−14.7% ± 21.1% v +5.0% ± 18.1%, P < .01), and the lag phase prolonged (+15.4% ± 24.4% v −0.1% ± 16.0%, P < .05) compared with placebo and basal values. The antioxidant potential of grape seed extract polyphenols may prove effective in a model of oxidative stress (smoking); however more investigational data are needed before use in wider clinical settings.

Elucidation of CYP2E1 5' regulatory RsaI/Pstl allelic variants and their role in risk for oral cancer.

The CYP2E1 gene, whose protein product plays an important role in the metabolism of various carcinogens, exhibits two polymorphisms recognized by the restriction enzymes RsaI and PstI in its transcriptional regulatory region that have been previously implicated in cancer susceptibility. In this study, we have examined these polymorphisms to elucidate CYP2E1 allelic haplotype, examining the prevalence of these CYP2E1 alleles in Caucasians and African Americans and their potential role in risk for oral cancer. In addition to the c1 (RsaI[+]/PstI[-]) and c2 (RsaI[-]/PstI[+]) alleles reported in previous studies, we have identified two new alleles, c3 (RsaI[+]/PstI[+]) and c4 (RsaI[-]/PstI[-]). The prevalence of the c2 and c3 alleles differs between racial groups, with African Americans exhibiting a lower prevalence of the c2 allele (0.003) but a higher prevalence of the c3 allele (0.049) than Caucasians (0.031 for c2 and 0.004 for c3). Of the 570 subjects screened in this study, the c4 allele was observed in one subject, a Caucasian case with the (c4/c4) genotype. A significant increase in the CYP2E1 (c1/c1) genotype was observed in oral cancer cases as compared to frequency-matched controls in subjects who smoked < or =24 pack-years (P=0.033). No association was observed between CYP2E1 genotype and risk for oral cancer in the heavy-smoking group (i.e. > 24 pack-years). Similar trends were observed for both Caucasians and African Americans. These data suggest that the c1 allele may contribute to increased risk for oral cancer.

Glutathione S-transferase T1-null genotype interacts synergistically with heavy smoking on lung cancer risk.

We studied the influence of genotype for glutathione S-transferase T1 (GSTT1) on susceptibility to lung cancer among 184 Swedish lung cancer patients (88 never-smokers and 96 ever-smokers) and 162 matched population controls (79 never-smokers and 83 ever-smokers), with special emphasis on gene-environment interactions. Cases had significantly lower frequency of the GSTT1-null genotype than that of controls among never-smokers (4.6 vs. 16.5%, P = 0.02), whereas the frequencies were very close to each other among smokers (7.4 vs. 7.2%). Cases with high packyears of smoking, however, had a significantly higher frequency of the GSTT1-null genotype compared to that of cases with low packyears (18.3 vs. 5.6%, P = 0.005). Adjusted for age and gender, the GSTT1-null genotype appeared to be protective against lung cancer among never-smokers (odds ratio [OR] = 0.2, 95% confidence interval [CI] = 0.07-0.7), although it was associated with an increased risk for lung cancer among smokers (OR = 2.1, 95% CI = 0.8-5.9), mainly attributed to the group of heavy smokers (>23 packyears; OR = 3.5, 95% CI = 0.7-17.3). Heavy smoking conferred a threefold increased risk for lung cancer (OR = 2.6, 95% CI = 1.3-5.0) among GSTT1-positive individuals, but a ninefold increased risk when combined with the GSTT1-null genotype (OR = 9.3, 95% CI = 1.9-46.3, relative to GSTT1-positive light smokers). This joint effect was further demonstrated by a positive interaction between the GSTT1-null genotype and packyears of smoking. The risk of lung cancer increased steeply with increasing packyears among GSTT1-null smokers, whereas no such effect was seen among GSTT1-positive smokers. We conclude that the GSTT1-null genotype may strengthen the effect of heavy smoking on lung cancer risk.

Association Between p53 Immunostaining and Cigarette Smoking in Squamous Cell Carcinoma of the Esophagus

It is generally accepted that cigarette smoking is closely associated with esophageal squamous cell carcinoma. This study investigated the molecular targets of cigarette smoke in carcinogenesis of the esophagus. Seventy-four patients with esophageal squamous cell carcinoma (SCC) were grouped according to daily cigarette consumption: heavy smoking group (group H) (n = 26), moderate smoking group (group M) (n = 39) and non-smoking group (group N) (n = 9). We compared p53 and retinoblastoma (RB) expression among the three groups by immunohistochemistry. In addition, fresh tumor tissues from 30 smokers with esophageal SCC were tested for p53 mutations in exons 5-8 by direct sequencing. Staining for the p53 product was positive in 65.4% of group H, 38.5% of group M and 44.4% of group N. The frequency of positive staining in the group H was significantly higher than in group M (p = 0.033) and in group M + group N (p = 0.034). The difference with respect to the frequency of overexpression of RB was not significant. The patterns of p53 base-pair mutations in direct sequencing study were of five types, most commonly G:C to T:A transversion (35.3%). Our study suggests that one of the molecular targets of cigarette smoke is the p53 gene. The pattern of p53 point mutations involved a wide range of base-pair changes.

Z and S mutations of the alpha1-antitrypsin gene and the risk of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) has been associated with heterozygosity for the Z and S alleles of the alpha1-antitrypsin gene in some studies, but these observations have not been confirmed by others. Cigarette smoking is the major risk factor for COPD and may have been a confounding factor in many of the previous studies. We investigated whether the Z or S alleles were more prevalent in a group of heavy smokers with COPD than in a group of nonobstructed smokers. Forced expiratory volume in 1 s and forced vital capacity were derived for 266 patients undergoing lobar or lung resection. These lung-function measurements were used to divide the patients into a COPD group and a group of nonobstructed control subjects. The subjects were typed for the Z and S alleles of the alpha1-antitrypsin gene using a polymerase chain reaction-based technique. In the COPD patients, 12 of 193 (6%) were heterozygous for the Z allele (MZ) compared with 0 of 73 control subjects, which gave a P value of 0.04 after correction for age, gender, and smoking history. There was no association of the S allele with COPD. The results indicate that the Z, but not the S, allele is a risk factor for COPD in the heterozygous state.

Stem villous arteries from the placentas of heavy smokers: Functional and mechanical properties

Objective: The aim of the study was to compare the mechanical and functional properties of isolated small stem villous arteries from the placentas of women who smoked heavily (≥15 cigarettes/d) during pregnancy with those from the placentas of nonsmokers. Study Design: Isolated stem villous arteries were mounted in small-vessel myographs. Circumference-tension relationships were established with 124 mmol/L potassium chloride. Concentration-response curves were obtained for endothelin 1, prostaglandin F 2α , vasoactive intestinal peptide, corticotropin-releasing hormone, sodium nitroprusside, and cadmium chloride. The effect of nitric oxide was examined with N ω-nitro- l -arginine. Results: Stem villous arteries from the heavy smoking group developed a significantly lower tension than did those from nonsmokers at 6 of 9 steps of the circumference-tension experiment ( P < .05). Endothelin 1 evoked a significantly greater maximum vasoconstrictive response in stem villous arteries from heavy smokers than in those from nonsmokers ( P < .05). Conclusion: Stem villous arteries of heavy smokers have altered mechanical properties and a greater vasoconstrictive response to endothelin 1 than do those from nonsmokers. These changes may compromise fetal placental blood flow and thereby contribute to the lower birth weights seen among infants born to heavy smokers. (Am J Obstet Gynecol 1999;180:476-82.)

Peculiarities of the GSTM1 0/0 genotype in French heavy smokers with various types of chronic bronchitis.

A homozygous gene deletion of the glutathione S-transferase M1 (GSTM1) locus of genomic DNA from blood spots was studied by the polymerase chain reaction in a group of French heavy smokers (n = 361), which included patients with severe chronic bronchitis (SCB; n = 87), moderate chronic bronchitis (MCB: n = 102) and hard smokers (HS) with no permanent clinical symptoms of chronic bronchitis (n = 172). The GSTM1 0/0 genotype was found in 71.3% and 65.7% of cases in SCB and MCB, respectively, compared with only 47.1% in the control HS group (P = 0.0002). This latter figure (47.1%) is consistent with the average GSTM1 deletion frequency in French Caucasians. Moreover, the results showed a significant difference in the distribution of the GSTM1 0/0 genotype for both the SCB and MCB groups against the control HS group, according to gender (SCB: P = 0.001; MCB: P = 0.005), age (SCB: P = 0.0001; MCB: P = 0.005) and smoking history (SCB: P = 0.0001; MCB: P = 0.005). Thus, individuals homozygous for the GSTM1 gene deletion, especially in the under-41 age group (SCB: P = 0.001; MSB: P = 0.04) with an average smoking history of 16-30 pack-years (SCB: P = 0.002; MSB: P = 0.01) are more prone to chronic lung diseases, such as SCB and MCB, than are GSTM1 +/+ or 0/+ subjects. Population screening of young people for the identification of GSTM1 0/0 subjects, with special emphasis on smoking habits, might be useful (1) for the early detection of individuals at high risk of lung complications caused by environmental toxins and pollutants and (2) in clinical practice, in order to prevent the development of chronic bronchitis, which is a common disease.

Occupational exposure to polycyclic aromatic hydrocarbons and the risk of bladder cancer: a French case-control study.

The risk of bladder cancer has been shown to be increased in occupations which are likely to involve exposure to polycyclic aromatic hydrocarbons (PAH), but up to now, most studies have considered this exposure in terms of job title. A hospital-based case-control study of 658 male cases of bladder cancer and 658 male controls was carried out in five areas of France from 1984 to 1987. For each subject, occupational exposure to PAH was assessed from questionnaires by an expert according to a semi-quantitative index of exposure. The overall odds ratio for PAH exposure, adjusted for smoking, coffee drinking and occupational exposure to aromatic amines was estimated at 1.3 (95% CI: 1.0-1.7, P < 0.05). A slight but clear dose-response relationship was observed, and the trend remained significant after adjustment for cumulative smoking, with odds ratios of 1.2 (95% CI: 0.9-1.7), 1.4 (95% CI: 0.9-2.2) and 1.8 (95% CI: 0.8-3.9) for low, medium and high average exposures respectively compared to subjects unexposed to PAH (P for trend < 0.05). Moreover, the association between bladder cancer and PAH exposure was also investigated in a category of smokers homogeneous with respect to their tobacco consumption. In this heavy-smoker group, a stronger association with PAH was detected. These results support the hypothesis of a causal relationship between occupational exposure to PAH and bladder cancer risk.

Warfarin dosage following prosthetic valve replacement: effect of smoking history.

Warfarin currently is the most widely used agent in the prevention of thrombosis and embolism after prosthetic cardiac valve replacement. Since smoking has been shown to increase the requirement for medications undergoing hepatic metabolism, this study was designed to determine if a correlation exists between smoking history and warfarin daily maintenance dose (DMD) in patients undergoing cardiac valve replacement. Of 200 charts retrospectively reviewed at the New England Medical Center, 174 satisfied the criteria for inclusion in the study (normal hepatic, renal, and hematologic function, and absence of complicating medications). The study population included aortic, mitral, and combined valve replacement. Study groups consisted of 117 nonsmokers (Group A), 23 light smokers (Group B), and 34 heavy smokers (Group C). Thirty-three percent of patients required a low DMD of warfarin (less than or equal to 2.5 mg), 43 percent required a moderate DMD (greater than 2.5-7.5 mg), and 24 percent required a high DMD (greater than 7.5 mg). Each of the subgroups followed a similar pattern. In Group A, there were 31 percent low, 44 percent moderate, and 25 percent high-dose requiring patients. In Group B, there were 48 percent low, 39 percent moderate, and 13 percent high-dose requiring patients and in Group C there were 29.5 percent low, 41 percent moderate, and 29.5 percent high-dose requiring patients. Chi-square analysis did not demonstrate any statistically significant difference between smokers and nonsmokers in regard to daily maintenance warfarin dose (p = 0.5). The study population followed a normal pattern of distribution in regard to warfarin dosage. On the basis of these data we conclude that smoking history does not affect warfarin dose requirement.

Nicotine intake by snuff users.

Blood nicotine and cotinine concentrations were measured in 27 volunteers before and after taking snuff. Within 10 minutes after snuffing blood nicotine concentrations were comparable to those obtained after the 10 minutes or so that it takes to smoke a cigarette. Nicotine intake from snuffing was related to the experience of the snuffer. In daily and occasional snuffers increases in plasma nicotine concentrations averaged 77.7 and 12.3 nmol/l (12.6 and 2.0 ng/ml) respectively, while the novices showed no appreciable increase. The increase shown by thea daily snuffers was comparable to the average increase of 62.3 nmol/l (10.1 ng/ml) obtained from a single cigarette by a group of heavy smokers. The peak nicotine concentrations in the daily snuffers were also similar to the peak values in 136 heavy smokers--222.6 and 226-3 nmol/l (36.1 and 36.7 ng/ml), respectively. Unusual multiple-dose snuffing produced massive increases in plasma nicotine to concentrations that have never been recorded in smokers. The similarity of the concentrations produced by regular daily snuffing and regular daily smoking suggests that the plasma nicotine concentration has some controlling influence over the self-regulation of these two quite different forms of tobacco use. The rapid absorption of nicotine from snuff confirms its potential as an acceptable and relatively harmless substitute for smoking.

Cigarette-Smoking Effect on Platelet Function

The immediate effect of cigarette-smoking on ADP-induced platelet aggregation and on platelet adhesiveness was investigated in 12 normal subjects aged 20 to 40, in 10 normal subjects aged 43 to 72 and in 10 patients with cerebrovascular disease aged 45 to 75. All the subjects were heavy smokers (more than 20 cigarettes a day). After smoking 2 cigarettes a significant increase in ADP aggregation and platelet adhesiveness was found in the group of young heavy smokers, while in the old subjects with or without cerebrovascular disease the increase in platelet activity was never significant. These data were discussed and some hypotheses for this higher reactivity of platelets from young people were suggested.

Effect of cigarette smoking on lipids, lipoproteins, blood coagulation, fibrinolysis and cellular components of human blood

A group of 187 volunteers aged 30–60 years were divided into heavy and light smokers and non-smokers. Heavy smokers smoked over 20 cigarettes per day and light smokers between 5–15, averaging about 7 cigarettes per day. 1. (1) Compared with male non-smokers (N.S.), the male heavy smokers (H.S.) had a higher fasting serum turbidity, higher levels of cholesterol (mainly confined to the ester cholesterol fraction) and higher levels of serum phospholipids and trigly cerides. In this H.S. group, the esterified fatty acid index (EFI) of beta and pre-beta lipoprotein were also raised as shown by paper and cellulose acetate electrophoresis. The Stypven clotting times were also shorter than for the N.S. group. 2. (2) Increased levels of triglycerides, pre-beta EFI, longer fibrinolysis times and shorter Stypven times were recorded in the group of female heavy smokers. Changes in cholesterol levels, beta EFI, phospholipids and fasting serum turbidity were not seen in this group. 3. (3) Again, in the male heavy smokers, haematocrit and haemoglobin levels and mean corpuscular volumes were raised. The white cell count (WBC) was very significantly raised and a differential count indicated rises in neutrophils and lymphocytes. These changes were not significant in the female H.S. group. 4. (4) No significant changes were found in the group of light smokers but a trend was usually seen that suggested that these changes were influenced by the number of cigarettes smoked.

Acute pulmonary effects of smoking a reference cigarette

The acute pulmonary effects of smoking a reference cigarette of known, standard composition have been studied in 30 subjects grouped according to their smoking habits. The results of selected ventilatory function tests did not change significantly after smoking. Inspiratory and expiratory lung airflow resistance was estimated before and after smoking by transiently occluding the subject's airway during tidal breathing, measuring the transairway pressure at the instant of interruption and relating the latter pressure to the rate of airflow recorded immediately prior to interruption. Control pulmonary resistance values obtained just prior to smoking were highest in the group of heavy smokers and in this group smoking produced a significant decrease in expiratory resistance to airflow. In nonsmokers inhalation of cigarette smoke resulted in a significant increase in expiratory resistance, but the site of the reduction in airway caliber was not determined.

Dissonance and desire for a cigarette.

Recent research has demonstrated that primary drives such as hunger, thirst, and pain can be affected by inductions of dissonance. The purpose of the present experiment was to determine whether an acquired drive, desire for a cigarette, could be similarly modified. 26 Ss were divided into two equal groups of heavy smokers. One group of Ss was paid $1.50 for 6 hr. of deprivation whereas the other group was not. It was hypothesized that highly dissonant Ss would show less drive-relevant behavior than low-dissonant Ss after deprivation. The results, though generally in the predicted direction, were not significant.