Vasoactive and atherogenic effects of cigarette smoking: a study of monozygotic twins discordant for smoking.

The mechanism by which atherosclerotic disease is induced by cigarette smoking has not yet been identified unequivocally. Chronic cigarette smoking and the generation of vasoactive prostanoids and the size of carotid atherosclerotic plaques were studied in nine pairs of identical male twins discordant for smoking for over 20 years. The urinary excretion of 2,3-dinor-thromboxane B2 (thromboxane B2 metabolite) of the smoking twin was significantly higher (on average 1.8 times higher) in every pair and that of 2,3-dinor-6-keto-prostaglandin F1 alpha (prostacyclin metabolite) was significantly higher (on average 1.3 times higher) in eight of the nine pairs. The ratio of excretion of these metabolites was significantly higher, being 4.0 (95% confidence interval 2.7 to 5.4) among the smokers compared with 2.9 (2.1 to 3.8) among the non-smokers, thus favouring a mechanism of vasoconstriction. Excretion of the thromboxane B2 metabolite was related to the urinary concentrations of nicotine metabolites. Atherosclerotic plaques detected by ultrasonography in the carotid arteries were significantly larger among smokers but did not correlate with the urinary excretion of prostacyclin and thromboxane B2 metabolites or intensity of smoking. Smoking was concluded to induce activation of platelets by an effect mediated by nicotine. The increased prostacyclin production, on the other hand, suggested a compensatory mechanism for the general vasoconstrictive properties of cigarette smoking.     

Influence of simultaneous low amniotomy and oxytocin infusion and other maternal factors on neonatal jaundice: a prospective study.

In a prospective study of 196 consecutive single births a significant increase in serum bilirubin concentrations was found in infants born after low amniotomy induction and oxytocin infusion compared with those born spontaneously. This relationship was not dose-dependent and may have been associated with artificial interruption of pregnancy rather than the oxytocin itself. Infants delivered after spontaneous labour accelerated by oxytocin showed no such increase. The hormonal surge at the spontaneous onset of labour may affect fetal enzyme induction, but other factors, such as methods of infant feeding and oral contraceptive use, were found not to be significant.     

Aspirin and coronary heart disease: findings of a prospective study.

Over 1 000 000 men and women answered a confidential questionnaire and were traced for up to six years afterwards. Among other questions each person was asked how often he or she took aspirin-"never", "seldom," or "often." Coronary heart disease death rates were no lower among people who took aspirin often than among those who did not do so.     

Active cigarette smoking and the risk of breast cancer: a cohort study

BackgroundTobacco use has been implicated in the etiology of a large number of cancers, and there exists substantial biological plausibility that it could also be involved in breast carcinogenesis. Despite this, epidemiological evidence to date is inconsistent. The aim of this study was to investigate the role of active smoking and the risk of incident, invasive breast cancer using a prospective cohort of women from the Canadian Study of Diet, Lifestyle and Health.MethodsUsing a case-cohort design, an age-stratified subcohort of 3314 women was created from 39,532 female participants who returned completed self-administered lifestyle and dietary questionnaires at baseline. A total of 1096 breast cancer cases were identified in the entire cohort (including 141 cases from the subcohort) by linkage to the Canadian Cancer Registry. Cox regression models were used to estimate hazard ratios for the association between the different smoking exposures and the risk of breast cancer, using a modification for the case-cohort design.ResultsAfter carefully considering early-life exposures and potential confounders, we found no association between any smoking exposure and risk of breast cancer in this study (Hazard ratio = 1.00, 95% confidence interval = 0.87–1.17 for ever vs never smokers).ConclusionsAlthough these results cannot rule out an association between smoking and breast cancer, they do agree with the current literature suggesting that, if an association does exist, it is relatively weak.     

Prospective study of cigarette smoking,alcohol use,and the risk of diabetes in men.

OBJECTIVE--To examine the association between smoking, alcohol consumption, and the incidence of non-insulin dependent diabetes mellitus in men of middle years and older. DESIGN--Cohort questionnaire study of men followed up for six years from 1986. SETTING--The health professionals'' follow up study being conducted across the United States. SUBJECTS--41,810 male health professionals aged 40-75 years and free of diabetes, cardiovascular disease, and cancer in 1986 and followed up for six years. MAIN OUTCOME MEASURE--Incidence of non-insulin dependent diabetes mellitus diagnosed in the six years. RESULTS--During 230,769 person years of follow up 509 men were newly diagnosed with diabetes. After controlling for known risk factors men who smoked 25 or more cigarettes daily had a relative risk of diabetes of 1.94 (95% confidence interval 1.25 to 3.03) compared with non-smokers. Men who consumed higher amounts of alcohol had a reduced risk of diabetes (P for trend < 0.001). Compared with abstainers men who drank 30.0-49.9 g of alcohol daily had a relative risk of diabetes of 0.61 (95% confidence interval 0.44 to 0.91). CONCLUSIONS--Cigarette smoking may be an independent, modifiable risk factor for non-insulin dependent diabetes mellitus. Moderate alcohol consumption among healthy people may be associated with increased insulin sensitivity and a reduced risk of diabetes.     

Disciplinary attitudes and cigarette smoking: a comparison of two schools.

Two British boarding schools for boys with different disciplinary policies in respect of cigarette smoking were identified. Questionnaires were sent to the young "old boys" of each school to determine their present smoking habit and most were returned (school A 81%, school B 83%). Significantly more responders smoked who had been to the less strict school (school A 39%, school B 30%, p less than 0.05). These figures probably underestimate the smoking prevalence in the two complete groups. The results suggest that measures that reduce the exposure of an uncommitted adolescent to peer group smoking decrease the chances of tobacco dependence in adulthood.     

Methylations in hemoglobin from monozygotic twins discordant for cigarette smoking: hereditary and tobacco-related factors.

Dose monitoring of exogenous methylators by measurement of N-methylvaline in hemoglobin (Hb) is rendered difficult due to a relatively high, variable background in unexposed persons. A kinetic study indicates intracellular S-adenosylmethionine to be a main source of these background methylations. A comparison of twin pairs indicates that the variation in methylvaline levels is partly hereditary (P less than 0.001). Therefore, in a study of monozygotic twin pairs discordant for tobacco smoking the resolving power of the monitoring was increased and in vivo doses of methylators from the smoke could be more easily monitored through their adducts to Hb. Probably, twin studies offer a useful tool for the identification and quantification of electrophiles of endogenous and exogenous origin.     

Effects of cigarette smoking on the human urinary proteome

In this pilot study we used a proteomic approach to compare the urinary protein patterns of healthy smokers and non-smokers. Proteins were resolved by two-dimensional gel electrophoresis and identified by mass spectrometry. The relative abundance of three inflammatory proteins (S100A8, inter-alpha-trypsin inhibitor heavy chain 4, CD59) and that of two isoforms of pancreatic alpha amylase was significantly higher in smokers. Zinc-alpha-2-glycoprotein was the only protein down-regulated in smokers. Its abundance was significantly correlated with urinary glucocorticoids. Most of the proteins identified may be non-specific biomarkers of tobacco effects, since they are involved in inflammatory responses associated with several diseases. Of greater interest are the changes in abundance of pancreatic alpha amylase and zinc-alpha-2-glycoprotein, which after proper validation, might be candidate biomarkers of diseases resulting from exposure to tobacco smoke. The data also show for the first time that smoking can affect the expression profile of urinary proteins.     

Effects of cigarette smoking, XRCC1 genetic polymorphisms, and age on basal DNA damage in human blood mononuclear cells

The aim of this study was to investigate the effects of smoking, polymorphisms of XRCC1 codons 194 and 399, and age on levels of basal DNA damage (as measured by an alkaline comet assay) on mononuclear cells in 122 healthy Japanese workers. In the whole group of 122 individuals, the tail moment (TM) values of current smokers (P < 0.001) or former smokers (P = 0.03) were significantly higher than those of nonsmokers. Individuals bearing the XRCC1 399Gln variant allele showed significant increases in TM values in all subjects or in referent subgroups stratified by age or smoking status except in the current smokers group; in contrast, the TM values of individuals bearing the XRCC1 194Trp variant allele were significantly lower than those of individuals bearing wild-type Arg/Arg genotypes. Furthermore, older subjects (≥47 years old) had significantly higher TM values than younger subjects (<47 years old) in all subjects (P = 0.008). Multiple regression analysis indicated that smoking habits, polymorphisms of XRCC1 codons 194 and 399, and age were important variables affecting individuals basal DNA damage.     

Environmental and other factors influencing fertility in Sri Lanka

The study utilizes the complete tabulations from the 1971 census and data from the Registrar General's and Meteorological departments for the same year. It applies a multiple regression analysis of the total fertility rate for each district for 1971 on a series of environmental variables. These include the proportion of the rural population by district to the all-island rural population; the district mean annual rainfall and the proportion of the district population employed in the major rural occupations to the total employed. To these 3 environmental variables were added 2 socioeconomic variables: the proportion of the population aged 10+ years and who are literate, and infant mortality. Results indicate that the 5 independent variables are clearly intercorrelated. The multiple regression analysis shows that the 5 variables together account for 76.4% of the total variation in district total fertility rate. It is argued that this and other studies undertaken previously provide useful pointers to the type of variable to be considered in any policy aimed at population control and indicate where major efforts should be directed.     

Effect of cigarette smoking on gastric emptying.

Gastric emptying after a test meal was studied in 17 normal volunteers--10 habitual smokers and seven non-smokers. The solid component of the test meal was labelled with technetium and the liquid component with indium. After one meal the habitual smokers smoked two cigarettes. Emptying curves were produced for both technetium and indium, and the differences between curves for meals with and without cigarettes were analysed. Cigarette smoking accelerated the rate at which the liquid component of a meal left the stomach. This may be important in the pathogenesis of duodneal ulcer and the delay in healing caused by cigarette smoking.     

Bulky DNA adducts in human sperm: relationship with fertility,semen quality,smoking, and environmental factors

The integrity of DNA of spermatogenic cells can be affected by endogenous and exogenous genotoxic factors. Resulting DNA damage in spermatozoa may significantly contribute to impaired fertility. Here, the 32P-postlabeling method was used to analyze the levels of bulky DNA adducts in sperm cells in a group of 179 males, either healthy donors or patients with an impaired fertility. When all donors were analyzed, the levels of bulky DNA adducts was 1.2-fold higher in smokers than in non-smokers, but the difference was not statistically significant (P=0.054). However, a statistically significant difference existed between current smokers and never smokers among the healthy individuals (1.7-fold increase, P=0.008). No correlation between alcohol or coffee consumption and sperm DNA adducts was found. The levels of DNA adducts in sperm seemed to be unaffected by environmental and occupational factors. On the other hand, groups of healthy persons and patients with male-factor infertility differed significantly with respect to the level of bulky DNA adducts (P=0.012). A significant negative correlation between DNA adducts and sperm concentration or sperm motility existed among patients with an impaired fertility (n=93; P<0.029, r(S)=-0.225). These results suggest that DNA adducts in sperm cells can be applied as potential biomarkers in studies of human infertility.     

Pelvic inflammatory disease and the intrauterine device: findings in a large cohort study.

The incidence of pelvic inflammatory disease was investigated among parous women taking part in the Oxford-Family Planning Association contraceptive study. Hospital admission rates for "acute definite" disease were 1.51 per 1000 woman-years among those currently using an intrauterine device (IUD) and 0.14 per 1000 woman-years among those using other methods of birth control (age-standardised relative risk 10.5 to 1 with 95% confidence limits of 5.4 to 1 and 32 to 1). There was little evidence of an increased risk of such disease in ex-users of an IUD. Hospital admission for "chronic definite" disease, on the other hand, was commoner in ex-users of an IUD than in current users. Acute definite disease occurred somewhat more frequently during the early months of use of an IUD than during the later months. While the rate of such disease was increased in users of each type of device, the highest rate (8.1 per 1000 woman-years) was observed in users of the Dalkon shield. This rate, however, was based on only three affected women.     

Effects of inbreeding and other genetic components on equine fertility

The Finnish mating records of Standardbred trotters (SB; n = 33 679) and Finnhorses (FH; n = 32 731) were analysed to study the effect of the level of inbreeding on foaling rates and to estimate the heritability of foaling rate. A linear mixed model was assumed, with the outcome of the foaling (foal or no foal) as the trait of the study. A restricted maximum likelihood-based method was used to calculate the estimates of the variance components. Predictions of breeding values and estimates of fixed effects were also calculated. The average level of inbreeding was 9.9% in the SB and 3.6% in the FH. The average foaling rates were better in the SB (72.6%) than in the FH (66.3%), but within each breed intense inbreeding had a statistically significant negative effect on foaling rate (P < 0.05). Also, the mating type, the age and breeding type of the mare, and the age of the stallion had statistically significant effects on foaling rate (P < 0.001). The heritability of foaling rate was between 3.4% and 3.7% in SBs and between 5.5% and 9.8% in FHs, when the outcome of the foaling was considered to be a trait of the expected foal. With the same model, the estimates of maternal genetic effect were 4.7% for SBs and 3.2% for FHs, and the estimates of the permanent environmental effects of the stallion were between 1.3% and 1.7%. Avoiding matings with very high inbreeding coefficients would improve foaling rates. It would also be possible to devise a breeding program for better equine fertility, but because the heritability is low, improvement of environmental factors deserves special attention.     

Maternal cigarette smoking, Down syndrome in live births, and infant race.

Previous studies have suggested that maternal smoking is negatively associated with a Down syndrome live birth. We analyzed the data of the U.S. Perinatal Collaborative Study in a search for racial variation in Down syndrome risk factors. There were 22 cases in 25,346 live births to smoking mothers (4/10,780 blacks, 18/13,320 whites, and 0/1,246 other races) and 42/29,130 live births to nonsmoking mothers (24/14,665 blacks, 14/11,694 whites, and 4/2,771 others). The crude overall rates per 1,000 live births were 0.4 in black smokers and 1.6 in black nonsmokers but 1.4 in white smokers and 1.2 in white non-smokers. Adjusted for maternal age, the summary relative risk for a Down syndrome live birth to a smoking mother was 0.2 in blacks (95% interval 0.1-0.7) but 1.2 in whites (95% interval 0.6-2.5). Stratification on variables associated with socioeconomic status or gestational age at time of entry into the study did not alter the racial difference. A comparison of smokers with those who never smoked revealed essentially the same trends. Among all nonsmokers the ratio of the maternal age-adjusted risks for a Down syndrome live birth in whites compared with blacks was 0.7 (95% interval 0.3-1.3), and among all smokers this ratio was 3.6 (95% interval 1.3-9.9). If the results are not attributable to statistical fluctuation or undetected confounding, then differences in the probability of intrauterine survival of the Down syndrome fetus would appear to be one plausible explanation for the difference.     

Effects on birth weight of smoking,alcohol, caffeine,socioeconomic factors,and psychosocial stress.

OBJECTIVE--To investigate the effects of smoking, alcohol, and caffeine consumption and socio-economic factors and psychosocial stress on birth weight. DESIGN--Prospective population study. SETTING--District general hospital in inner London. PARTICIPANTS--A consecutive series of 1860 white women booking for delivery were approached. 136 Refused and 211 failed to complete the study for other reasons (moved, abortion, subsequent refusal), leaving a sample of 1513. Women who spoke no English, booked after 24 weeks, had insulin dependent diabetes, or had a multiple pregnancy were excluded. MEASUREMENTS--Data were obtained by research interviewers at booking (general health questionnaire, modified Paykel''s interview, and Eysenck personality questionnaire) and at 17, 28, and 36 weeks'' gestation and from the structured antenatal and obstetric record. Variables assessed included smoking, alcohol consumption, caffeine consumption, and over 40 indicators of socio-economic state and psychosocial stress, including social class, tenure of accommodations, education, employment, income, anxiety and depression, stressful life events, social stress, social support, personality, and attitudes to pregnancy. Birth weight was corrected for gestation and adjusted for maternal height, parity, and baby''s sex. MAIN RESULTS--Smoking was the most important single factor (5% reduction in corrected birth weight). Passive smoking was not significant (0.5% reduction). After smoking was controlled for, alcohol had an effect only in smokers and the effects of caffeine became non-significant. Only four of the socioeconomic and stress factors significantly reduced birth weight and these effects became non-significant after smoking was controlled for. CONCLUSIONS--Social and psychological factors have little or no direct effect on birth weight corrected for gestational age (fetal growth), and the main environmental cause of its variation in this population was smoking.