Co-expression of polyhydroxyalkanoate synthase and (R)-enoyl-CoA hydratase genes of Aeromonas caviae establishes copolyester biosynthesis pathway in Escherichia coli

Arylamine N-acetyltransferase 2 (NAT2) is involved in both the detoxification and bioactivation of carcinogenic arylamines and other mutagens. This enzyme is polymorphic, and the fast and slow phenotypes are thought to be risk factors for colon and bladder cancer, respectively. Here, we report on a case-control study of adenomatous and hyperplastic polyps, with particular attention to tobacco smoking, a known risk factor for adenomas, and polymorphisms of NAT2. All participants underwent complete colonoscopy and were subsequently divided into case and control groups on the basis of pathology. Cases were diagnosed with confirmed adenomas (n = 527) or hyperplastic polyps (n = 200); controls (n = 633) had no history of colonic neoplasia and no polyps at colonoscopy. NAT2 genotype was determined using an oligonucleotide ligation assay and fast, intermediate, or slow phenotype imputed. Multivariate-adjusted odds ratios (ORs) and 95% confidence intervals were computed using logistic regression adjusting for age, sex, nonsteroidal anti-inflammatory drug use, and hormone replacement therapy use. Smoking was associated with an increased risk of adenomas [current versus never smoking OR = 2.0 (95% confidence interval, 1.4-2.9)] and hyperplastic polyps [current versus never smoking OR = 4.1 (2.6-6.5)]. NAT2 status among adenomatous polyp patients and hyperplastic polyp patients, respectively, showed ORs of 1.1 (0.8-1.4) and 1.2 (0.8-1.6; intermediate versus slow) and 1.1 (0.6-1.9) and 0.9 (0.4-1.9; fast versus slow). There were no differences in risk when adenoma patients were stratified on multiplicity, size, or histopathological subtype of polyps. Never-smokers showed no variation in risk across acetylator status for either species of polyp, whereas current smokers showed ORs of 2.0 (1.2-3.2) and 2.3 (1.4-3.9) for adenomas and 3.9 (2.1-7.1) and 4.9 (2.6-9.4) for hyperplastic polyps for slow and intermediate/fast NAT2, respectively, compared with slow-NAT2 never-smokers. Risks of both multiple [OR = 4.3 (2.1-8.8)] and large [OR = 3.8 (1.9-7.5)] adenomas were somewhat elevated in current smokers with an intermediate/fast phenotype compared with smokers with a slow NAT2 phenotype, but the interaction was not statistically significant. Risk of hyperplastic polyps and adenomatous polyps is strongly related to smoking. There is little suggestion of interaction between NAT2 status and smoking and no relationship with NAT2 genotype alone.     

Cigarette smoking, bacterial pneumonia, and other clinical outcomes in HIV-1 infection. Terry Beirn Community Programs for Clinical Research on AIDS

Cigarette smoking has been associated with impaired immune defenses and an increased risk of certain infectious and neoplastic diseases in HIV-1 seronegative populations. We examined the relationship between cigarette smoking and clinical outcome in a prospective cohort of 3221 HIV-1-seropositive men and women enrolled in the Terry Beirn Community Programs for Clinical Research on AIDS. Differences in clinical outcomes between never, former, and current cigarette smokers were assessed using proportional hazards regression analysis. After adjustment for CD4+ cell count, prior disease progression, use of antiretroviral therapy, and other covariates, there was no difference between current smokers and never smokers in the overall risk of opportunistic diseases [relative hazard (RH) = 1.05; 95% confidence interval (CI) 0.90-1.23; p = 0.52] or death (RH = 1.00; 95% CI 0.86-1.18; p = 0.97). However, current smokers were more likely than never smokers to develop bacterial pneumonia (RH = 1.57; 95% CI 1.14-2.15; p = 0.006), oral candidiasis (RH = 1.37; 95% CI 1.16-1.62; p = 0.0002), and AIDS dementia complex (RH = 1.80; 95% CI 1.11-2.90; p = 0.02). In addition, current smokers were less likely to develop Kaposi's sarcoma (RH = 0.58; 95% CI 0.39-0.88; p = 0.01) and several other non-respiratory tract diseases. If confirmed by other studies, these findings have important clinical implications.     

Benign symmetrical lipomatosis: Madelung''s disease

The relationship between smoking and bladder cancer risk was investigated using data from a case-control study conducted between January 1994 and July 1996 in Alexandria, Egypt. Cases were 151 males with incident, histologically confirmed invasive cancer of the bladder, and controls were 157 males admitted to hospital for acute, non-neoplastic, non-urinary tract, non-smoking-related conditions. With reference to never smokers, ex-smokers had a multivariate odds ratio (OR) of 4.4 [95% confidence interval (CI) 1.7-11.7] and current smokers of 6.6 (95% CI 3.1-13.9). The ORs were 5.4 for < 20 and 7.6 for > or = 20 cigarettes per day. After adjustment for cigarette smoking, the ORs were 0.8 for waterpipe and 0.4 for hashish smokers. The risk was significantly related to duration of smoking (OR of 16.5 for > 40 years), and inversely related to age at starting (OR of 8.8 for starting < 20 years), and inversely related to time since quitting smoking. Compared with never smokers who did not report a clinical history of schistosomiasis, the OR was 9.4 for smokers with a history of schistosomiasis, and 10.7 for smokers ever employed in high-risk occupations compared with non-smokers not reporting such a history. Thus, our results, while not giving indications of an increased bladder cancer risk with habits other than cigarette smoking, found a remarkably strong association with various measures of cigarette smoking that could explain 75% of bladder cancer cases among males from Alexandria. The prevalence of smoking was very low among women, and consequently tobacco was not a relevant risk factor for female bladder cancer.     

Age-related macular degeneration and smoking. The Rotterdam Study

OBJECTIVE: To assess the relation between cigarette smoking and age-related macular degeneration (AMD) in a population of elderly persons. DESIGN: A cross-sectional, community-based study. SETTING: City district of Rotterdam, the Netherlands. PARTICIPANTS: A total of 6174 persons 55 years and older who participated in the Rotterdam Study. In 36 persons atrophic AMD and in 65 persons neovascular AMD were diagnosed. MAIN OUTCOME MEASURES: Age-related macular degeneration was diagnosed by evaluating fundus transparencies, smoking behavior was identified by interviewing subjects, and the presence of atherosclerosis was assessed by the ankle-arm systolic blood pressure index. Relative risks and 95% confidence intervals (CIs) were calculated using multivariate logistic regression analysis. RESULTS: In subjects younger than 85 years, current smokers had a 6.6-fold increased risk of neovascular AMD vs those who had never smoked (95% CI, 2.8-15.9). Former smokers had a 3.2-fold increased risk of neovascular AMD vs nonsmokers in this age group (95% CI, 1.4-7.4). These associations were not observed in subjects 85 years or older. Smoking was not associated with atrophic AMD. A strong increased risk of neovascular AMD was present in those who had smoked more than 10 pack-years (relative risk, 6.5; 95% CI, 2.9-14.8). Adjusting the results for atherosclerosis did not change the association. Persons who had quit smoking 20 or more years before the eye examination had no increased risk. CONCLUSIONS: The results provide evidence for a dose-response relationship between smoking and AMD, particularly in persons with the neovascular form of the disease.     

Alcohol, smoking, and cataracts: the Blue Mountains Eye Study

OBJECTIVE: To investigate the associations between alcohol consumption, tobacco smoking, and cataract. DESIGN: A population-based, cross-sectional study. SETTING: An urban community in the Blue Mountains, close to Sydney, Australia. PARTICIPANTS: Three thousand six hundred fifty-four people aged 49 to 97 years. The participation rate was 82%. MAIN OUTCOME MEASURES: Smoking history and details of current alcohol consumption were assessed by questionnaire. Lens photographs were taken and graded for presence and severity of cortical, nuclear, and posterior subcapsular cataracts. RESULTS: After adjusting for multiple potential confounders, people who had ever smoked cigarettes had a higher prevalence than nonsmokers of more severe nuclear (adjusted odds ratio [OR], 1.3; 95% confidence interval [CI], 1.1-1.6) and posterior subcapsular (adjusted OR, 1.5; 95% CI, 1.1-2.1) cataracts. The association between pipe smoking and nuclear cataract (adjusted OR, 3.1; 95% CI, 1.5-8.2) was stronger than the association with cigarette smoking. Alcohol consumption was associated with a reduced prevalence of cortical cataract: compared with people who did not drink, the adjusted OR for cortical cataract among people who drank at least 1 drink a day was 0.7 (95% CI, 0.6-0.9). Heavy alcohol consumption (> or =4 drinks a day) was associated with nuclear cataract in current smokers (adjusted OR compared with nondrinkers, 3.9; 95% CI, 0.9-16.6) but not in never smokers. CONCLUSIONS: Consistent with other studies, smoking was associated with a higher prevalence of nuclear and posterior subcapsular cataracts. The only adverse effect of alcohol was among smokers: people who smoked and drank heavily had an increased prevalence of nuclear cataract.     

Prospective study of exogenous hormones and risk of pulmonary embolism in women

BACKGROUND: Current use of oral contraceptives (OCs) is a well-recognised risk factor for venous thrombosis and consequent pulmonary embolism (PE). Little is known about residual effects of past OC use. Furthermore, few epidemiological studies have assessed the relation between postmenopausal use of hormones and thrombotic disease. METHODS: In this prospective study information was obtained through questionnaires sent every 2 years (1976-92) to 1125,93 women aged 30-55 in 1976. We excluded women with previously diagnosed cardiovascular disease or cancer in 1976 and at the beginning of each subsequent 2-year follow-up period. FINDINGS: From self-reports and medical records, we documented 123 cases of primary PE (no identified antecedent cancer, trauma, surgery, or immobilisation). Current users of postmenopausal hormones had an increased risk of primary PE (relative risk adjusted for multiple risk factors 2.1 [95% CI 1.2-3.8]). However, past use showed no relation to PE (1.3 [0.7-2.4]). In current users of OCs the risk of primary PE was about twice that in non-users (2.2 [0.8-5.9]), but this finding was based on only five cases who were current OC users. Users of OCs in the past had no increase in risk of PE (0.8 [0.5-1.2]). These relations were consistent irrespective of cigarette-smoking status. INTERPRETATION: Primary PE was uncommon in this cohort. The risk was increased by current though not past use of postmenopausal hormones or OCs.     

Effects of smoking on the urine excretion of oral 51Cr EDTA in ulcerative colitis

BACKGROUND: Smokers have a reduced risk and ex-smokers an increased risk of ulcerative colitis (UC). Stopping smoking often precedes onset and relapses. Smoking reduces the 24 hour urine excretion of oral chromium-51 labelled EDTA in healthy individuals. AIMS: To estimate the effects of smoking on the urine excretion of oral 51Cr EDTA in well characterised patients with UC. SUBJECTS: Sixteen smoking and 16 non-smoking patients with UC in remission were studied. The non-smokers had never smoked. Most were taking 5-aminosalicylic acid. No patient took steroids or immunosuppressants. The control group comprised 25 smoking healthy volunteers and 25 who had never smoked. The median cigarette consumption was equal in the patients and volunteers. METHODS: The 24 hour urine excretion of oral 51Cr EDTA was measured and the results were correlated with smoking habits, number of cigarettes, and disease extent. RESULTS: Patients with UC had significantly higher 24 hour urine recoveries than healthy controls (p = 0.04). This difference was more pronounced when patients who smoked were compared with healthy smokers (p = 0.005) No significant differences were found when comparing non-smoking patients with non-smoking controls or when comparing smoking and non-smoking patients. Urine recoveries did not correlate with number of cigarettes or disease extent. Smoking was more prevalent in patients with a more limited disease extent (p = 0.033). CONCLUSIONS: Effects of smoking on the urine excretion of 51Cr EDTA in health were abolished by the presence of UC. The protective effects of smoking in established UC are not due to a moderating effect of smoking on intestinal permeability.     

Glutathione S-transferase mu1 and N-acetyltransferase 2 genetic polymorphisms and exposure to tobacco smoke in nonsmoking and smoking lung cancer patients and population controls

We conducted a case-control study to assess the risk of lung cancer in relation to genetic polymorphisms of the detoxifying enzymes glutathione-S-transferase mu1 (GSTM1) and N-acetyl transferase 2 (NAT2), focusing on never-smokers, women, and older people. The study base consisted of persons > or =30 years of age in Stockholm County from 1992 to 1995. We recruited never-smoking lung cancer cases and a sex- and age-matched sample of ever-smoking cases at the three county hospitals mainly responsible for diagnosing and treating lung cancer. A total of 185 cases (25.4% men; 47.6% never-smokers) and 164 frequency-matched population controls (28.7% men; 48.2% never-smokers) supplied blood for genotyping. Detailed information was collected by interview on active and passive smoking, occupations, residences, and diet. The overall odds ratio (OR) for lung cancer associated with the GSTM1 null (GSTM1-) versus GSTM1+ genotype was 0.8 [95% confidence interval (CI), 0.5-1.2], with an OR close to unity among smokers, and lower ORs suggested among never-smokers. For NAT2 slow versus rapid acetylator genotypes, the OR was 1.0 (95% CI, 0.6-1.5) overall, which broke down into an increased risk for slow acetylators among never-smokers but an increased risk for rapid acetylators among smokers. Among never-smokers, a gene interaction was suggested, with combined slow acetylator and GSTM1+ genotype conferring particularly high risk (OR = 3.1; 95% CI, 1.1-8.6), but no clear pattern emerged among smokers. A detailed analysis among smokers showed no interaction between pack-years of smoking and the GSTM1 genotype but suggested a steeper increase in risk with increasing pack-years of smoking exposure for rapid than for slow acetylators. Our results do not support a major role for the GSTM1 genetic polymorphism as a risk factor for lung cancer among smokers or nonsmokers. There was, however, some suggestion that the slow acetylator genotype may confer an increased risk among never-smokers and that the rapid acetylator genotype interacts with pack-year dose to produce a steeper risk gradient among smokers.     

Effect of a chronic high-salt diet on whole-body and organ sodium contents of Dahl rats

A prior history of depression and the epsilon 4 allele of apolipoprotein E (APOE) have each been associated with development of Alzheimer's disease (AD). In a sample of 142 elderly twins from a large study of dementia, we examined the relation of major depression, APOE genotype and AD using time-dependent proportional hazards models. Compared against the risk for AD with no history of depression and no epsilon 4 allele, the risk ratio for AD with two epsilon 4 alleles was 2.87 (C.I. = 1.56-5.28), with one epsilon 4 allele, 1.82 (C.I. = 1.09-3.04) and with late-onset depression and no epsilon 4 allele, 2.95 (C.I. = 1.55-5.62). There was no suggestion of an interaction between prior depression and APOE genotype in their effects on AD risk. Results were similar when the sample was stratified by twin pair, so that a single genetic marker is unlikely to explain the relation among depression, APOE, and dementia. Risk ratios declined substantially with increasing intervals between the onset of depression and AD. Thus, for many individuals, the association of depression and AD may reflect the occurrence of prodromal depressive symptoms rather than a true risk relationship.     

Prospective study of effect of switching from cigarettes to pipes or cigars on mortality from three smoking related diseases

OBJECTIVE: To estimate the extent to which cigarette smokers who switch to cigars or pipes alter their risk of dying of three-smoking related diseases-lung cancer, ischaemic heart disease, and chronic obstructive lung disease. DESIGN: A prospective study of 21520 men aged 35-64 years when recruited in 1975-82 with detailed history of smoking and measurement of carboxyhaemoglobin. MAIN OUTCOME MEASURES: Notification of deaths (to 1993) classified by cause. RESULTS: Pipe and cigar smokers who had switched from cigarettes over 20 years before entry to the study smoked less tobacco than cigarette smokers (8.1 g/day v 20 g/day), but they had the same consumption as pipe and cigar smokers who had never smoked cigarettes (8.1 g) and had higher carboxyhaemoglobin saturations (1.2% v 1.0%, P < 0.001), indicating that they inhaled tobacco smoke to a greater extent. They had a 51% higher risk of dying of the three smoking related diseases than pipe or cigar smokers who had never smoked cigarettes (relative risk 1.51; 95% confidence interval 0.96 to 2.38), a 68% higher risk than lifelong non-smokers (1.68; 1.16 to 2.45), a 57% higher risk than former cigarette smokers who gave up smoking over 20 years before entry (1.57; 1.04 to 2.38), and a 46% lower risk than continuing cigarette smokers (0.54; 0.38 to 0.77). CONCLUSION: Cigarette smokers who have difficulty in giving up smoking altogether are better off changing to cigars or pipes than continuing to smoke cigarettes. Much of the effect is due to the reduction in the quantity of tobacco smoked, and some is due to inhaling less. Men who switch do not, however, achieve the lower risk of pipe and cigar smokers who have never smoked cigarettes. All pipe and cigar smokers have a greater risk of lung cancer than lifelong non-smokers or former smokers.     

Establishment of xenografts and cell lines from well-differentiated human thyroid carcinoma

OBJECTIVE: To investigate the acute effect of cigarette smoking on glucose tolerance, insulin sensitivity, serum lipids, blood pressure, and heart rate. RESEARCH DESIGN AND METHODS: This nonrandomized experimental control trial in a tertiary care center included 20 healthy chronic smokers and 20 age-, sex-, and BMI-matched healthy volunteers. Two oral glucose tolerance tests (OGTTs) were performed on each subject. Three cigarettes were smoked during the first 30 min in one of the tests. Serum glucose, insulin, and C-peptide levels were measured every 30 min; the area under the curve (AUC) and the insulin sensitivity index (ISI) were calculated; serum total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels were measured at 0 and 180 min; and blood pressure and heart rate were recorded every 5 min throughout 180 min. RESULTS: Smoking acutely impaired glucose tolerance: the AUC for glucose in smokers was 25.5 +/- 1.03 mmol/l (mean +/- SE) (95% CI 22.9-28) during the smoking OGTT and 21.8 +/- 0.85 mmol/l (CI 19.2-24.3) in the control OGTT (P < 0.01); in nonsmokers, it was 19.7 +/- 0.3 mmol/l (CI 18.8-20.5) in the smoking OGTT and 18.7 +/- 0.35 mmol/l (CI 17.8-19.5) in the control OGTT (P < 0.05). Smoking acutely increased serum insulin and C-peptide levels and decreased ISI only in smokers: ISI in smokers was 55 +/- 2.8 (CI 47.4-62.6) in the control OGTT and 43 +/- 2.7 (CI 35.4-50.6) in the smoking OGTT (P < 0.05). Smoking acutely caused a rise of serum total cholesterol levels in both groups and increased LDL cholesterol and triglyceride serum levels significantly only in smokers (P < 0.05). A significant rise of blood pressure and heart rate while smoking was present in all the subjects. CONCLUSIONS: Smoking acutely impaired glucose tolerance and insulin sensitivity, enhanced serum cholesterol and triglyceride levels, and raised blood pressure and heart rate. These findings support the pathogenetic role of cigarette smoking on cardiovascular risk factors.     

Lapse-induced surges in craving influence relapse in adult smokers: An experimental investigation.

Objectives: Nearly all smokers who lapse experience a full-blown relapse, but the mediating mechanisms that contribute to this relationship are not well understood. A better understanding of these mechanisms would help to advance more effective relapse prevention treatments for smokers. The purpose of this study is to experimentally evaluate the effects of a programmed smoking lapse on smoking relapse and the effects of postlapse changes in craving on relapse. Method: Adult smokers (n = 63) who quit smoking with a brief cognitive–behavioral intervention and self-help materials were randomly assigned to one of two experimental conditions after 48 h of abstinence: No lapse (a no-smoking control/30-min waiting period) or lapse (smoking two cigarettes of their favored brand during a 30-min period). All participants were then followed daily for 14 days. Craving and biochemically verified self-reported abstinence were assessed on each follow-up day. Time (days) to relapse (7 consecutive days of smoking) was the main dependent measure. Results: Results of Cox regression analysis revealed that participants in the lapse condition relapsed more quickly than participants in the no-lapse condition (hazard ratio [HR] = 2.12, 95% confidence interval [CI] = [1.03, 4.35]). These effects were attributable, in part, to episodic increases in craving among participants in the lapse condition only (HR = 12.42, 95% CI =[2.00, 77.1]). Conclusions: Previously abstinent smokers who lapse are at risk for increased cigarette cravings and consequently, full-blown relapse. These results have implications for both cognitive–behavioral treatments for relapse prevention and for medications designed to help smokers manage cravings. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Confocal laser scanning microscopy of chondrocytes in vitro: cytoskeletal changes after quinolone treatment

CONTEXT: Whether tobacco advertising and promotion increases the likelihood that youths will begin smoking has important public policy implications. OBJECTIVE: To evaluate the association between receptivity to tobacco advertising and promotional activities and progress in the smoking uptake process, defined sequentially as never smokers who would not consider experimenting with smoking, never smokers who would consider experimenting, experimenters (smoked at least once but fewer than 100 cigarettes), or established smokers (smoked at least 100 cigarettes). DESIGN: Prospective cohort study with a 3-year follow-up through November 1996. SETTING AND PARTICIPANTS: A total of 1752 adolescent never smokers who were not susceptible to smoking when first interviewed in 1993 in a population-based random-digit dial telephone survey in California were reinterviewed in 1996. MAIN OUTCOME MEASURE: Becoming susceptible to smoking or experimenting by 1996. RESULTS: More than half the sample (n=979) named a favorite cigarette advertisement in 1993 and Joe Camel advertisements were the most popular. Less than 5% (n=92) at baseline possessed a promotional item but a further 10%(n=172) were willing to use an item. While having a favorite advertisement in 1993 predicted which adolescents would progress by 1996 (odds ratio [OR] = 1.82; 95% confidence interval [CI], 1.04-3.20), possession or willingness to use a promotional item was even more strongly associated with future progression (OR=2.89; 95% CI, 1.47-5.68). From these data, we estimate that 34% of all experimentation in California between 1993 and 1996 can be attributed to tobacco promotional activities. Nationally, this would be over 700000 adolescents each year. CONCLUSION: These findings provide the first longitudinal evidence to our knowledge that tobacco promotional activities are causally related to the onset of smoking.     

Validation of susceptibility as a predictor of which adolescents take up smoking in the United States.

Smoking onset has 4 levels, with a "susceptibility" level preceding early experimentation. This study assessed the predictive validity of smoking susceptibility in a longitidinal study of a nationally representative sample of 4,500 adolescents who at baseline reported never having puffed on a cigarette. At follow-up 4 yrs later, 40% of the sample had experimented with smoking, and 8% had established a smoking habit. Baseline susceptibility to smoking, defined as the absence of a firm decision not to smoke, was a stronger independent predictor of experimentation than the presence of smokers among either family or the best friend network. However, susceptibility to smoking was not as important as exposure to smokers in distinguishing adolescents who progressed to established smoking from those who remained experimenters at follow-up. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The asbestos worker who smokes: Adding insult to injury.

Evaluated differences among 129 asbestos workers who currently smoke cigarettes or who choose not to smoke on demographic, personality, psychological, and cognitive measures. Smoking was related exclusively to cognitive factors. Although current smokers were cognitively aware of their added health risk, in comparison to past smokers and Ss who had never smoked, they minimized the salience of awareness by fatalistically attributing their health to chance factors and by minimizing the dangers of smoking, the benefits of smoking cessation, and their own increased vulnerability to life-threatening illnesses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contemporary knowledge on the subject of visual cortex structure and function

BACKGROUND: Cigarette smoking is a major risk factor for developing coronary artery disease and is associated with increased coronary morbidity and mortality in patients with established atherosclerosis. This report describes the influence of smoking on coronary endothelial function in normotensive patients with coronary artery disease, but without left ventricular dysfunction, severe hypercholesterolemia, or insulin-dependent diabetes mellitus. METHODS: Placebo-treated patients (n = 54) from a larger study assessing coronary endothelial function were classified at baseline as smokers or nonsmokers for this subgroup analysis. Patients underwent coronary angiography at baseline and again after 6-month follow-up. RESULTS: At baseline, there was a trend for a greater decrease in target segment diameter (n = 54) in smokers compared with nonsmokers (-17.2 +/- 5.3% vs. -8.0 +/- 2.5%, acetylcholine 10(-4) mol/l). All measured coronary artery segments (n = 202) showed similar responses (-7.3 +/- 2.7% vs. -3.8 +/- 1.3%, acetylcholine 10(-4) mmol/l, for smokers vs. nonsmokers, respectively). After 6 months, smokers showed an even greater vasoconstrictor response to acetylcholine whereas nonsmokers did not (-21.7 +/- 5.3% vs. -8.3 +/- 2.5%, acetylcholine 10(-4) mmol/l). The vasodilatory response to nitroglycerin was similar in smokers and nonsmokers. CONCLUSIONS: In current smokers, a marked decline in endothelium-dependent vasomotor response was observed over a 6-month period.     

The effects of smoking on bone mass and the rates of bone loss among elderly Japanese-American men

Bone density and bone loss rates were examined among Japanese-American men categorized as current cigarette smokers, past smokers, and nonsmokers. The design included a retrospective study of smoking and bone density and a prospective study of current smoking and bone loss rates. The mean length of follow-up was 5 years; the setting was the island of Oahu. The subjects included 1303 men in the Hawaii Osteoporosis Study, 51-82 years old at their initial examination. Twenty percent were current smokers, 45% past smokers, and 35% had never smoked. Their bone density was measured at the distal and proximal radius and calcaneus using single photon absorptiometry. Compared with never smokers, current and past smokers had significantly lower bone density, especially in the predominantly cancellous calcaneus (4.8 and 4.3% lower, respectively) and partially trabecular distal radius (1.8 and 3.3% lower, respectively). The magnitude of the smoking effect was linked strongly to the duration of smoking and also to the number of cigarettes smoked. Bone loss rates subsequent to the initial measurement were greater in the current smokers than the never smokers (20.5, 27.2, and 9.7% greater at the calcaneus, distal, and proximal radius, respectively) but the differences did not achieve significance. Smokers of more than one pack per day had 32.0, 77.6, and 30.7% greater loss rates than never smokers in these same sites; the difference achieved significance at the distal radius. The results from the distal radius suggest that these smokers may increase their fracture risk 10-30% per decade of smoking. The adverse effects of smoking appeared to be greater in cancellous than cortical bone.     

Influence of the smoking habit in the surgery of inflammatory bowel disease

The smoking habit is a key factor in the development of inflammatory bowel disease (IBD), but little information exists as to the relationship between smoking habit, the need of surgery and its complications. OBJECTIVES: To investigate the relationship between smoking habit, the need of surgery, their complications and clinical recurrence after surgery in Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We studied a group of 62 patients (22 with UC and 40 with CD) with previous surgery. We analyzed the clinical and surgical characteristics of the disease. Smoking habit was established by a personal interview. This group of patients was compared with another control group of 202 patients (133 with UC and 69 with CD) with IBD without previous surgery. RESULTS: Smoking habit was similar between operated and non-operated patients for both UC (73% and 80% non-smokers) and CD (67% and 63% smokers) The number and type of complications after surgery were not related with smoking habit. In CD patients, although the recurrences did not depend on the smoking habit, they did occur earlier in smokers than in non smokers (83.6 +/- 21 vs 155 +/- 50 weeks, p = ns). CONCLUSIONS: The smoking habit does not seem to influence significantly the need of surgery and post surgical development of IBD, although in CD the smokers seems to present recurrence before non smokers.     

Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer's disease. Alzheimer's Disease Centers Consortium on Apolipoprotein E and Alzheimer's Disease

BACKGROUND: The epsilon4 allele of the gene encoding apolipoprotein E (APOE) is strongly associated with Alzheimer's disease, but its value in the diagnosis remains uncertain. METHODS: We reviewed clinical diagnoses and diagnoses obtained at autopsy in 2188 patients referred to 1 of 26 Alzheimer's disease centers for evaluation of dementia. The sensitivity and specificity of the clinical diagnosis or the presence of an APOE epsilon4 allele were calculated, with pathologically confirmed Alzheimer's disease used as the standard. The added value of the APOE genotype was estimated with pretest and post-test probabilities from multivariate analyses to generate receiver-operating-characteristic curves plotting sensitivity against the false positive rate. RESULTS: Of the 2188 patients, 1833 were given a clinical diagnosis of Alzheimer's disease, and the diagnosis was confirmed pathologically in 1770 patients at autopsy. Sixty-two percent of patients with clinically diagnosed Alzheimer's disease, as compared with 65 percent of those with pathologically confirmed Alzheimer's disease, had at least one APOE epsilon4 allele. The sensitivity of the clinical diagnosis was 93 percent, and the specificity was 55 percent, whereas the sensitivity and specificity of the APOE epsilon4 allele were 65 and 68 percent, respectively. The addition of information about the APOE genotype increased the overall specificity to 84 percent in patients who met the clinical criteria for Alzheimer's disease, although the sensitivity decreased. The improvement in specificity remained statistically significant in the multivariate analysis after adjustment for differences in age, clinical diagnosis, sex, and center. CONCLUSIONS: APOE genotyping does not provide sufficient sensitivity or specificity to be used alone as a diagnostic test for Alzheimer's disease, but when used in combination with clinical criteria, it improves the specificity of the diagnosis.     

Effect of smoking on breast cancer in carriers of mutant BRCA1 or BRCA2 genes

BACKGROUND: Smoking has carcinogenic effects, and possibly antiestrogenic effects as well, but it has not been found to be a risk factor for breast cancer in women in the general population. However, hereditary breast cancer is primarily a disease of premenopausal women, and interactions between genes and hormonal and environmental risk factors may be particularly important in this subgroup. METHODS: We conducted a matched case-control study of breast cancer among women who have been identified to be carriers of a deleterious mutation in either the BRCA1 or the BRCA2 gene. These women were assessed for genetic risk at one of several genetic counseling programs for cancer in North America. Information about lifetime smoking history was derived from a questionnaire routinely administered to women who were found to carry a mutation in either gene. Smoking histories of case subjects with breast cancer and age-matched healthy control subjects were compared. Odds ratios for developing breast cancer were determined for smokers versus nonsmokers by use of conditional logistic regression for matched sets after adjustment for other known risk factors. RESULTS: Subjects with BRCA1 or BRCA2 gene mutations and breast cancer were significantly more likely to have been nonsmokers than were subjects with mutations and without breast cancer (two-sided P = .007). In a multivariate analysis, subjects with BRCA1 or BRCA2 mutations who had smoked cigarettes for more than 4 pack-years (i.e., number of packs per day multiplied by the number of years of smoking) were found to have a lower breast cancer risk (odds ratio = 0.46, 95% confidence interval = 0.27-0.80; two-sided P = .006) than subjects with mutations who never smoked. CONCLUSIONS: This study raises the possibility that smoking reduces the risk of breast cancer in carriers of BRCA1 or BRCA2 gene mutations.