***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND It is generally accepted that smoking increases blood pressure and inhibits muscle sympathetic nerve activity ( SNA ) . The decrease in muscle SNA with cigarette smoking might be secondary to baroreflex responses to the pressor effect of smoking , thus obscuring a sympathetic excitatory effect of smoking . We tested the hypothesis that smoking increases sympathetic outflow . METHODS AND RESULTS We examined the effects of sham smoking , cigarette smoking , and cigarette smoking in combination with nitroprusside on muscle ( baroreflex-dependent ) SNA in 10 healthy habitual smokers . The 3 sessions were performed in r and om order , each study on a separate day . In an additional study , we also investigated the effects of sham smoking and cigarette smoking on skin ( baroreflex-independent ) SNA in 9 subjects . Compared with sham smoking , cigarette smoking alone increased blood pressure and decreased muscle SNA . When the blood pressure increase in response to smoking was blunted by nitroprusside infusion , there was a striking increase in muscle SNA . Muscle SNA increased up to 3-fold the levels seen before smoking ( P<0.001 ) , accompanied by an increase in heart rate of up to 37+/-4 bpm . Cigarette smoking also induced a 102+/-22 % increase in skin SNA ( P=0.03 ) . CONCLUSIONS These data provide the first direct evidence that cigarette smoking increases sympathetic outflow Cigarette smoking is associated with impaired endothelium‐dependent dilatation in human veins and arteries . An in vivo study in animals suggests that nicotine may contribute to this abnormality . We tested the hypothesis that local administration of nicotine at a dose reproducing the plasma concentration observed during smoking would impair endothelium‐dependent vasodilatation in human veins in vivo Using a reliable , newly developed assay for ascorbic acid ( reduced form ) and dehydroascorbic acid ( DHAA ; the oxidized form ) in plasma , we studied the influence of age , sex , and smoking on 219 healthy , age-stratified , and r and omly selected subjects representing the Danish population . The mean ( + /-SD ) plasma total ascorbic acid ( ascorbic acid + DHAA ) concentration was lower in smokers ( 62.8 + /- 24.9 mumol/L ) than in nonsmokers ( 74.9 + /- 23.6 mumol/L ) ( P < 0.001 ) and the DHAA content was 1.8 + /- 4.0 % of the total ascorbic acid in smokers compared with 0.1 + /- 3.1 % in nonsmokers ( P < 0.001 ) . A significant inverse correlation between the DHAA fraction and the total ascorbic acid concentration was found in smokers ( P < 0.002 ) but not in smokers ; the slopes of the linear regressions were significantly different in the two groups ( P < 0.005 ) . The mean plasma concentration of total ascorbic acid was higher in females than in males ( P < 0.005 ) ; this difference persisted in multivariate analysis when smoking was adjusted for . No age dependence could be identified . The data show that smoking results in severe oxidative stress , depletion of the ascorbic acid pool , and insufficient reduction capacity to maintain ascorbic acid in the reduced form in plasma . We suggest that the additional analysis of DHAA allows further differentiation in the assessment of oxidative stress and may provide an objective way of determining vitamin C requirements in smokers . Preliminary findings suggest that a vitamin C dose that results in a plasma concentration of approximately 70 mumol/L or higher is required in smokers BACKGROUND An association between smoking and impaired wound healing has been reported in retrospective studies . The smoking status of a surgical patient may be confounded by social and medical parameters . We have evaluated the effect of smoking in a test wound in volunteers , with special reference to a reliable scientific match between smokers and nonsmokers . METHODS In a prospect i ve open study with blinded assessment , 19 smoking ( 20 cigarettes/day ) and 18 nonsmoking healthy volunteers were matched with respect to baseline characteristics . The deposition of total protein and mature collagen ( expressed as hydroxyproline ) was assessed in an exp and ed polytetrafluoroethylene wound healing model implanted subcutaneously for 10 days . RESULTS The nonsmokers had a 1.8 times higher median amount of hydroxyproline than the smokers ( p < 0.01 ) . The deposition of hydroxyproline was negatively correlated with the consumption of tobacco both before ( r = -0.44 ; p < 0.01 ) and during the study ( r = -0.48 ; p < 0.005 ) . The impairment was specific for the production of collagenous proteins and not other proteins . CONCLUSIONS The synthesis of subcutaneous collagen in smokers is specifically impeded , indicating an impaired wound-healing process . Because mature collagen is the main determinator of strength of an operative wound , the results support the view that patients should be advised to stop smoking before an operation Objective —The role of antioxidants in preventing vascular disease remains controversial . Vascular endothelial growth factor ( VEGF-A ) is important for endothelial and monocyte function . This study investigated the negative effects of smoking on monocyte migratory responsiveness to VEGF-A and the usefulness of vitamin C to prevent smoking-induced monocyte dysfunction . Methods and Results —The chemotactic response of isolated monocytes from a cohort of 17 non-smokers and 10 smokers toward VEGF-A was assessed . VEGF-A significantly stimulated the migration of monocytes in non-smokers ; the monocytes from smokers failed to respond to VEGF-A. Repeated analysis after 2 weeks of vitamin C intake ( 2g/d ) showed a fully restored VEGF-A – induced monocyte migration in smokers . VEGF-A serum levels were not altered by vitamin C.  VEGF-A – inducible kinase activity was intact in monocytes from smokers as assessed by in vitro kinase assay . Monocyte dysfunction can be mimicked in vitro by challenging monocytes with a range of reactive oxygen species ( ROS ) . Conclusions —Stimulation of monocyte migration by VEGF-A was severely attenuated in smokers , and the deficit observed was surmounted by vitamin C supplementation . The negative effects of smoking on monocyte function may translate into adverse impacts on VEGF-A – dependent repair processes such as arteriogenesis . These results propose a causative role of oxidative stress in smoking-induced monocyte dysfunction Higher white blood cell counts in smokers compared with nonsmokers have been well documented , but the longitudinal relation between changes in smoking and changes in white blood cells has not been well described . Since 1984 , data have been collected semiannually by the Multicenter AIDS Cohort Study ( MACS ) , a four-center prospect i ve cohort study of acquired immunodeficiency syndrome ( AIDS ) in homosexual men . The study population includes 2,435 participants who were human immunodeficiency virus ( HIV ) seronegative as of September 1994 and who contributed 20,918 person-visits for this analysis . For individuals who modified their smoking behavior , changes in white blood cell counts occurred primarily during the first 6 months following changes in the amount of cigarettes smoked . Among former smokers who resumed smoking , the extent of the increase in white blood cell count depended on the number of cigarettes smoked . Specifically , increases of 241 , 340 , and 740 cells/microliter were observed for smokers who resumed smoking < 1 , 1 to < 2 , and > or = 2 packs/day , respectively . Conversely , smokers who quit smoking had a decrease of white blood cell count : -32 , -629 , and -1,122 cells/microliter for men who previously smoked < 1 , 1 to < 2 , and > or = 2 packs/day , respectively . Long-term ex-smokers , however , still had higher white blood cell counts than did never smokers . There was a high within-individual correlation of white blood cell count in persons who reported a consistent level of smoking ( i.e. , average correlations between two white blood cell counts 6 years apart were 0.51 for never smokers , 0.48 for ex-smokers , 0.56 for men who smoked < 1 pack/day , and 0.43 for men who smoked > or = 1 pack/day ) . These analyses indicate an acute effect of changes in smoking on changes in white blood cell count , a residual effect of having been a smoker , and high long-term tracking for white blood cell count BACKGROUND Smokers are at higher risk of cardiopulmonary and wound-related postoperative complications than non-smokers . Our aim was to investigate the effect of preoperative smoking intervention on the frequency of postoperative complications in patients undergoing hip and knee replacement . METHODS We did a r and omised trial in three hospitals in Denmark . 120 patients were r and omly assigned 6 - 8 weeks before scheduled surgery to either the  control ( n=60 ) or smoking intervention ( 60 ) group .  Smoking intervention was counselling and nicotine replacement therapy , and either smoking cessation or at least 50 % smoking reduction . An assessor , who was masked to the intervention , registered the occurrence of cardiopulmonary , renal , neurological , or surgical complications and duration of hospital admittance . The main analysis was by intention to treat . FINDINGS Eight controls and four patients from the intervention group were excluded from the final analysis because their operations were either postponed or cancelled . Thus , 52 and 56 patients , respectively , were analysed for outcome . The overall complication rate was 18 % in the smoking intervention group and 52 % in controls ( p=0.0003 ) . The most significant effects of intervention were seen for wound-related complications ( 5 % vs 31 % , p=0.001 ) , cardiovascular complications ( 0 % vs 10 % , p=0.08 ) , and secondary surgery ( 4 % vs 15 % , p=0.07 ) . The median length of stay was 11 days ( range 7 - 55 ) in the intervention group and 13 days ( 8 - 65 ) in the control group . INTERPRETATION An effective smoking intervention programme 6 - 8 weeks before surgery reduces postoperative morbidity , and we recommend , on the basis of our results , this programme be adopted Delayed wound healing may explain postoperative tissue and wound dehiscence in smokers , but the effects of smoking and smoking cessation on the cellular mechanisms remain unclear . Suction blisters were raised in 48 smokers and 30 never smokers . The fluid was retrieved and the epidermal roof was excised . Transepidermal water loss ( TEWL ) was measured after 2 , 4 , and 7 days . Then , the smokers were r and omized to continuous smoking or abstinence with a transdermal nicotine patch or a placebo by concealed allocation . The sequence was repeated after 4 , 8 , and 12 weeks in all smokers and abstainers and in 6 never smokers .  Matrix metalloproteinase (MMP)-8 and MMP-1 levels in suction blister fluid were assessed by an enzyme-linked immunosorbent assay . R and om-effects models for repeated measurements were applied and p < or = 0.05 was considered significant . One week after wounding the TEWL was 17.20 ( 14.47 - 19.92 ) g/cm(2 ) hour ( mean , 95 % CI ) in smokers and 13.89 ( 9.46 - 18.33 ) in never smokers ( p<0.01 ) . In abstinent smokers TEWL was 18.95 (15.20 - 22.70)(p<0.01 , when compared with smokers ) . In smokers , MMP-8 was 36.4 ( 24.3 - 48.5 ) ng/mL ( mean , 95 % CI ) and 15.2 ( 1.4 - 30.2 ) ng/mL in never smokers ( p<0.01 ) . Abstinent smokers ' MMP-8 level was 21.2 ng/mL ( 6.6 - 43.0 ) ( p=0.02 , when compared with smokers ) . MMP-1 was unaffected by smoking and abstention . Transdermal nicotine patch did not affect any parameter . We conclude that smoking attenuates epidermal healing and may enhance extracellular matrix degradation . Three months of abstinence from smoking does not restore epidermal healing , whereas 4 weeks of abstinence normalizes suction blister MMP-8 levels . These findings suggest sustained impaired wound healing in smokers and potential reversibility of extracellular matrix degradation OBJECTIVES We sought to determine the effects of nicotine patch therapy , when used to promote smoking cessation , on myocardial ischemia in patients with coronary artery disease . BACKGROUND Nicotine patches substantially increase quit rates among cigarette smokers , but their safety in patients with myocardial ischemia who are attempting to quit smoking is unknown . METHODS This is a 
    Output:
    
RESULTS Smoking decreases tissue oxygenation and aerobe metabolism temporarily .
The inflammatory healing response is attenuated by a reduced inflammatory cell chemotactic responsiveness , migratory function , and oxidative bactericidal mechanisms .
In addition , the release of proteolytic enzymes and inhibitors is imbalanced .
The proliferative response is impaired by a reduced fibroblast migration and proliferation in addition to a downregulated collagen synthesis and deposition .
Smoking cessation restores tissue oxygenation and metabolism rapidly .
Inflammatory cell response is reversed in part within 4 weeks , whereas the proliferative response remains impaired .
Nicotine does not affect tissue microenvironment , but appears to impair inflammation and stimulate proliferation .
CONCLUSIONS Smoking has a transient effect on the tissue microenvironment and a prolonged effect on inflammatory and reparative cell functions leading to delayed healing and complications .
Smoking cessation restores the tissue microenvironment rapidly and the inflammatory cellular functions within 4 weeks , but the proliferative response remain impaired .
Nicotine and nicotine replacement drugs seem to attenuate inflammation and enhance proliferation but the effect appears to be marginal