Autoantigens PLA2R and THSD7A in membranous nephropathy share a common epitope motif in the N-terminal domain.

Patients with membranous nephropathy have autoantibodies against PLA2R (up to 80%), or THSD7A (up to 2%). We previously described the immunodominant epitope within PLA2R but epitopes in THSD7A are still unknown. To find anti-THSD7A sera for this study, we screened 1843 sera from biopsy-proven MN patients by ELISA and identified 22 sera as anti-THSD7A positive representing 1.2% of MN cases. Anti-THSD7A positive sera were further characterized by western blotting and slot blotting on THSD7A protein fragments and peptides. Real time interaction analyses and antibodies off-rate could be reliably determined using bio-layer interferometry. A signature motif in the N-terminal domain of THSD7A (T28mer) with sequence homology to the major PLA2R epitope (P28mer) was identified. B-cell epitope prediction analysis and homology modelling revealed this sequence to be antigenic and surface available suggesting it is accessible for the antibody to bind. All ten selected sera bound to the T28mer confirming this sequence as a dominant epitope in THSD7A. Reactivity to this sequence was lost following kallikrein protease cleavage within the predicted epitope. Importantly, cross-reactivity of both PLA2R and THSD7A autoantibodies was observed at the peptide but not the protein level. We propose that this common motif shared by both autoantigens could be an epitope involved in the initial B-cell triggering event in MN.

Assessing the incidence trend and characteristics of eosinophilic esophagitis in children in Olmsted County, Minnesota.

Previous studies reported increased eosinophilic esophagitis (EoE) incidence in children. It is unclear whether this reported increased EoE incidence is true or due to increased recognition and diagnostic endoscopy among children. A population-based study that evaluated EoE incidence in OC, Minnesota, from 1976 to 2005 concluded that EoE incidence increased significantly over the past three 5-year intervals (from 0.35 [range: 0-0.87] per 100,000 person-years for 1991-1995 to 9.45 [range: 7.13-11.77] per 100,000 person-years for 2001-2005). The aim of this study is to assess the change of incidence and characteristics of EoE in children in the same population between 2005 and 2015 and compare the findings to those reported in the previous study. We retrospectively reviewed the electronic medical records from Olmsted Medical Center and Mayo Clinic between 2005 and 2015, using Rochester Epidemiology Project (REP) resources. All children with EoE diagnosis based on the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) guidelines were included. The incidence and characteristics of children with EoE during the study period were compared to those diagnosed between 1995 and 2005. The incidence of EoE in children adjusted for age and sex was 5.31 per 100,000 population person-years in 1995, 15.2 in 2005, and 19.2 in 2015. Change in annual incidence and seasonal variation were not significant, (P = .48) and (P = .32), respectively. Between 2005 and 2015, 73 children received an EoE diagnosis (boys 49; 67%) compared to 16 children (boys 10; 62.5) between 1995 and 2005. Mean (SD) age at diagnosis was 7.5 (5.2) and 12.8 (4.3) years, respectively. Symptoms differed by age of presentation, with vomiting the most common in children younger than 5 years (41.1% and 43.5%) and dysphagia in those older than 5 years (35.6% and 60.9%). The incidence of EoE was not increased for any specific age-group during the study period (P = .49). This study showed increased incidence of EoE in children in Olmsted County between 2005 and 2015 compared to the incidence between 1995 and 2005 (5.31 per 100,000 population person-years in 1995, 15.2 in 2005, and 19.2 in 2015). However, between 2005 and 2015, the change of incidence was not statically significant, (P = .48) despite the steady increase of EGD performed during the same time frame (64 in 2005 to 144 in 2015). By comparing children diagnosed between 2005 and 2015 to those diagnosed between 1995 and 2005, the mean age at diagnosis was younger in the former group, 7.5 versus 12.8 years. Vomiting replaced dysphagia as the most common clinical presentation. Otherwise, the presenting symptom of EoE in children remained consistent across specific age groups.

Beneficial effects of polyphenol-rich olive oil in patients with early atherosclerosis.

PURPOSE: Diets rich in plant-derived polyphenols such as olive oil (OO) and/or catechins such as epigallocatechin 3-gallate (EGCG) have been shown to reduce the incidence of cardiovascular diseases, potentially by improving endothelial function, an important surrogate for atherosclerosis. The possible augmentation of endothelial function with the combined efforts of OO and EGCG is intriguing, yet unknown. METHODS: Eighty-two patients with early atherosclerosis (presence of endothelial dysfunction) were enrolled in this double-blind, randomized trial with 52 completing the study. The aim of the study was to compare the effect of a daily intake of 30 ml simple OO, with 30 ml of EGCG-supplemented OO, on endothelial function as well as on inflammation and oxidative stress after a period of 4 months. Endothelial function was assessed noninvasively via peripheral arterial tonometry (Endo-PAT®). RESULTS: After 4 months, when OO and EGCG-supplemented OO groups were combined, OO significantly improved endothelial function (RHI, 1.59 ± 0.25-1.75 ± 0.45; p < 0.05). However, there were no significant differences in results between the two olive oil groups. Interestingly, with OO supplementation there was a significant reduction in inflammatory parameters: sICAM (196 to 183 ng/mL, p = < 0.001); white blood cells (WBCs) (6.0 × 109/L-5.8 × 109/L, p < 0.05); monocytes (0.48 × 109/L to 0.44 × 109/L, p = 0.05); lymphocytes (1.85 × 109/L to 1.6 × 109/L, p = 0.01); and platelets (242-229 × 109/L, p = 0.047). CONCLUSIONS: Improvement in endothelial dysfunction in patients with early atherosclerosis in association with significant reduction in leukocytes may suggest an important role of early cellular inflammatory mediators on endothelial function. The current study supports one potential mechanism for the role of olive oil, independent of EGCG, modestly supplemented to a healthy cardiovascular diet.

Anti-Flavivirus Vaccines: Review of the Present Situation and Perspectives of Subunit Vaccines Produced in Escherichia coli.

This article aims to review the present status of anti-flavivirus subunit vaccines, both those at the experimental stage and those already available for clinical use. Aspects regarding development of vaccines to Yellow Fever virus, (YFV), Dengue virus (DENV), West Nile virus (WNV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV) are highlighted, with particular emphasis on purified recombinant proteins generated in bacterial cells. Currently licensed anti-flavivirus vaccines are based on inactivated, attenuated, or virus-vector vaccines. However, technological advances in the generation of recombinant antigens with preserved structural and immunological determinants reveal new possibilities for the development of recombinant protein-based vaccine formulations for clinical testing. Furthermore, novel proposals for multi-epitope vaccines and the discovery of new adjuvants and delivery systems that enhance and/or modulate immune responses can pave the way for the development of successful subunit vaccines. Nonetheless, advances in this field require high investments that will probably not raise interest from private pharmaceutical companies and, therefore, will require support by international philanthropic organizations and governments of the countries more severely stricken by these viruses.

Rosiglitazone enhances glucose uptake in glomerular podocytes using the glucose transporter GLUT1.

AIMS/HYPOTHESIS: Peroxisome proliferator-activated receptor (PPAR) gamma agonists are used increasingly in the treatment of type 2 diabetes. In the context of renal disease, PPARgamma agonists reduce microalbuminuria in diabetic nephropathy; however, the mechanisms underlying this effect are unknown. Glomerular podocytes are newly characterised insulin-sensitive cells and there is good evidence that they are targeted in diabetic nephropathy. In this study we investigated the functional and molecular effects of the PPARgamma agonist rosiglitazone on human podocytes. METHODS: Conditionally immortalised human podocytes were cultured with rosiglitazone and functional effects were measured with glucose-uptake assays. The effect of rosiglitazone on glucose uptake was also measured in 3T3-L1 adipocytes, nephrin-deficient podocytes, human glomerular endothelial cells, proximal tubular cells and podocytes treated with the NEFA palmitate. The role of the glucose transporter GLUT1 was investigated with immunofluorescence and small interfering RNA knockdown and the plasma membrane expression of GLUT1 was determined with bis-mannose photolabelling. RESULTS: Rosiglitazone significantly increased glucose uptake in wild-type podocytes and this was associated with translocation of GLUT1 to the plasma membrane. This effect was blocked with GLUT1 small interfering RNA. Nephrin-deficient podocytes, glomerular endothelial cells and proximal tubular cells did not increase glucose uptake in response to either insulin or rosiglitazone. Furthermore, rosiglitazone significantly increased basal and insulin-stimulated glucose uptake when podocytes were treated with the NEFA palmitate. CONCLUSIONS/INTERPRETATION: In conclusion, rosiglitazone has a direct and protective effect on glucose uptake in wild-type human podocytes. This represents a novel mechanism by which PPARgamma agonists may improve podocyte function in diabetic nephropathy.

Deliberate Self-Harm (DSH): a follow-up study of Irish children.

This study aimed to look at rates of repetition in children presenting with Deliberate Self-Harm (DSH) to a paediatric A&E department. Children presenting with DSH to a paediatric A&E between 2000 and 2005 were invited to participate in the study. Telephone interviews collected information on demographic details and mental health functioning, including repetition of DSH. Data was obtained from 39 parents and 10 children (31 girls and 8 boys, mean age 15) 1 in 5 females (20%) had made a repeat attempt of DSH and 1 in 10 (10%) had repeated more than once. No males repeated self-harm. On going parental concern rather than clinician risk assessment at index episode predicted subsequent DSH. Given the poor predictive value of clinician risk assessment, all attempts of DSH must be taken seriously, especially those associated with ongoing parental concern.

Are we following the European charter? Children, parents and staff perceptions.

BACKGROUND: In 1988, the European Association for Children in Hospital (EACH) established a charter of rights setting out the guiding principles for the treatment of children in hospital. Our aim was to ascertain whether children, parents and staff in a children's hospital believe the European Charter is conformed to. METHODS: A total of 111 parents (response rate = 90%), 50 children (response rate = 100%), 61 nurses (response rate = 55%) and 41 doctors (response rate = 25%) agreed to participate. Questionnaires based on the 10 rights in the EACH Charter were administered to children, parents and staff. RESULTS: The majority of children and parents were happy with the relationship they had with staff. However, the findings suggest that children, parents and staff are concerned with the lack of facilities in hospital, including parental accommodation, play, education, age-appropriate wards and lack of privacy. Staff felt that many children undergo unnecessary admission and treatment in hospital. Many staff are reluctant to discuss issues such as side effects of medications with patients and do not encourage children to ask questions. Contrary to expectations, clinicians were reluctant to consider children under 16 as capable of giving consent, and most parents and children felt that children should be over 17 and 18 respectively. CONCLUSION: This paper highlights patients' and staff's perceptions regarding children's rights in hospital and discusses the changes needed to fully conform to the EACH Charter.

Persistence and Intra-Host Genetic Evolution of Zika Virus Infection in Symptomatic Adults: A Special View in the Male Reproductive System.

We followed the presence of Zika virus (ZIKV) in four healthy adults (two men and two women), for periods ranging from 78 to 298 days post symptom onset. The patients were evaluated regarding the presence of the virus in different body fluids (blood, saliva, urine and semen), development of immune responses (including antibodies, cytokines and chemokines), and virus genetic variation within samples collected from semen and urine during the infection course. The analysis was focused primarily on the two male patients who shed the virus for up to 158 days after the initial symptoms. ZIKV particles were detected in the spermatozoa cytoplasm and flagella, in immature sperm cells and could also be isolated from semen in cell culture, confirming that the virus is able to preserve integrity and infectivity during replication in the male reproductive system (MRS). Despite the damage caused by ZIKV infection within the MRS, our data showed that ZIKV infection did not result in infertility at least in one of the male patients. This patient was able to conceive a child after the infection. We also detected alterations in the male genital cytokine milieu, which could play an important role in the replication and transmission of the virus which could considerably increase the risk of ZIKV sexual spread. In addition, full genome ZIKV sequences were obtained from several samples (mainly semen), which allowed us to monitor the evolution of the virus within a patient during the infection course. We observed genetic changes over time in consensus sequences and lower frequency intra-host single nucleotide variants (iSNV), that suggested independent compartmentalization of ZIKV populations in the reproductive and urinary systems. Altogether, the present observations confirm the risks associated with the long-term replication and shedding of ZIKV in the MRS and help to elucidate patterns of intra-host genetic evolution during long term replication of the virus.

Effect of Low-Dose Rapamycin on Senescence Markers and Physical Functioning in Older Adults with Coronary Artery Disease: Results of a Pilot Study.

Rapamycin, an mTOR inhibitor affects senescence through suppression of senescence-associated secretory phenotype (SASP). We studied the safety and feasibility of low-dose rapamycin and its effect on SASP and frailty in elderly undergoing cardiac rehabilitation (CR). 13 patients; 6 (0.5mg), 6 (1.0mg), and 1 patient received 2mg oral rapamycin (serum rapamycin <6ng/ml) daily for 12 weeks. Median age was 73.9±7.5 years and 12 were men. Serum interleukin-6 decreased (2.6 vs 4.4 pg/ml) and MMP-3 (26 vs 23.5 ng/ml) increased. Adipose tissue expression of mRNAs (arbitrary units) for MCP-1 (3585 vs 2020, p=0.06), PPAR-γ (1257 vs 1166), PAI-1 (823 vs 338, p=0.08) increased, whereas interleukin-8 (163 vs 312), TNF-α (75 vs 94) and p16 (129 vs 169) decreased. Cellular senescence-associated beta galactosidase activity (2.2% vs 3.6%, p=0.18) tended to decrease. We observed some correlation between some senescence markers and physical performance but no improvement in frailty with rapamycin was noted. (NCT01649960).

Obesity is independently associated with coronary endothelial dysfunction in patients with normal or mildly diseased coronary arteries.

OBJECTIVES: This study evaluates the impact of obesity on coronary endothelial function in patients with normal or mild coronary artery disease. BACKGROUND: The American Heart Association (AHA) has recently classified obesity as a modifiable risk factor for coronary heart disease. METHODS: A total of 397 consecutive patients with normal or mildly diseased coronary arteries at angiography underwent coronary vascular reactivity evaluation using intracoronary adenosine, acetylcholine and nitroglycerin. Patients were divided into three groups based on the body mass index (BMI): Group 1, patients with a BMI <25 (n = 117, normal weight); Group 2, patients with a BMI 25-30 (n = 149, overweight) and Group 3, patients with a BMI >30 (n = 131, obese). RESULTS: There were no significant differences among the groups in regard to other cardiovascular risk factors, except that overweight but not obese patients were significantly older than normal-weight patients (47 +/- 1 years in Group 1, 53 +/- 1 years in Group 2 and 50 +/- 1 years in Group 3, p < 0.001). The percent change of coronary blood flow to acetylcholine (%delta CBF Ach) was significantly lower in the obese patients than in the normal-weight group (85.2 +/- 12.0% in Group 1, 63.7 +/- 10.0% in Group 2 and 38.1 +/- 9.6% in Group 3, p = 0.009). By multivariate analysis, overweight (odds ratio, 1.55; 95% confidence interval, 1.2-2.0) and obesity (odds ratio, 2.41; 95% confidence interval, 1.5-4.0) status were independently associated with impaired coronary endothelial function. CONCLUSIONS: The study demonstrates that obesity is independently associated with coronary endothelial dysfunction in patients with normal or mildly diseased coronary arteries.

Anti-flavivirus vaccines: review of the present situation and perspectives of subunit vaccines produced in escherichia coli

This article aims to review the present status of anti-flavivirus subunit vaccines, both those at the experimental stage and those already available for clinical use. Aspects regarding development of vaccines to Yellow Fever virus, (YFV), Dengue virus (DENV), West Nile virus (WNV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV) are highlighted, with particular emphasis on purified recombinant proteins generated in bacterial cells. Currently licensed anti-flavivirus vaccines are based on inactivated, attenuated, or virus-vector vaccines. However, technological advances in the generation of recombinant antigens with preserved structural and immunological determinants reveal new possibilities for the development of recombinant protein-based vaccine formulations for clinical testing. Furthermore, novel proposals for multi-epitope vaccines and the discovery of new adjuvants and delivery systems that enhance and/or modulate immune responses can pave the way for the development of successful subunit vaccines. Nonetheless, advances in this field require high investments that will probably not raise interest from private pharmaceutical companies and, therefore, will require support by international philanthropic organizations and governments of the countries more severely stricken by these viruses

Percutaneous coronary interventions in patients with prior coronary artery bypass surgery: changes in patient characteristics and outcome during two decades.

PURPOSE: Patients who develop recurrent myocardial ischemia after coronary artery bypass graft (CABG) surgery are often referred for percutaneous coronary interventions. The objective of this study was to evaluate the changing demographic and clinical characteristics, and procedural and long-term outcomes, in patients with prior CABG referred for percutaneous coronary interventions during a 20-year period. METHODS: We prospectively collected data on patients who underwent coronary interventional procedures following CABG surgery. We compared angiographic and procedural success, and long-term event-free survival, among patients who had procedures from 1979 to 1989 (n = 393), from 1990 to 1994 (n = 811), and from 1995 to 1998 (n = 937). RESULTS: Patients in the 1995 to 1998 cohort were older, had a lower mean left ventricular ejection fraction, and were more likely to have diabetes, hypertension, and hyperlipidemia, but less likely to smoke. They were more likely to have treatment of complex lesions, including vein graft lesions, and had more prior CABG surgeries. More patients received intracoronary stents in 1995 to 1998. Both angiographic success rates (78% from 1979 to 1989, 88% from 1990 to 1994, and 91% from 1995 to 1998, P < 0.0001) and procedural success rates (78%, 86%, and 91%, P < 0.0001) improved with time. Long-term mortality was greater in the pre-1990 group (relative risk = 1.8, 95% confidence interval: 1.3 to 2.4) and 1990 to 1994 group (relative risk = 1.7, 95% confidence interval: 1.3 to 2.2) compared with the 1995 to 1998 group, as were the likelihoods of repeat revascularization and recurrent severe angina. CONCLUSION: Although the demographic and clinical characteristics of patients who underwent percutaneous intervention following CABG surgery indicate that they are at increasingly greater risk of adverse cardiac events, success rates and long-term survival have improved with time. The rates of recurrent severe angina as well as of subsequent revascularization have also decreased, probably as a result of improvements in technique and greater use of stents and adjunctive medications.

Comparison of percutaneous interventions for unstable angina pectoris in patients with and without previous coronary artery bypass grafting.

An increasing number of patients who have undergone previous coronary artery bypass grafting (CABG) are referred for percutaneous coronary revascularization. We identified patients who underwent percutaneous intervention for unstable angina from 1990 to 1998 at our institution and assigned them into 2 groups based on whether or not they had undergone previous CABG. There were 1,431 patients with and 4,629 patients without previous CABG. Previous CABG patients were older, had more atherosclerotic risk factors, more heart failure, lower ejection fraction, more multivessel disease, more multilesion treatment, more complex lesions, and less complete revascularization. Adjusting for baseline differences, previous CABG was associated with worse long-term mortality (RR 1.47, 95% confidence intervals [CI] 1.22 to 1.77, p < 0.001) and death, myocardial infarction, and/or revascularization (RR 1.16, 95% CI 1.04 to 1.30, p = 0.01); treatment of native lesions in patients with previous CABG versus treatment of vein graft lesions was associated with a reduction in this composite end point (RR 0.75, 95% CI 0.65 to 0.87, p < 0.001). Post-CABG patients treated between 1995 and 1998 had lower long-term mortality (RR 0.76, 95% CI 0.59 to 0.99, p = 0.04) and death, myocardial infarction, and/or revascularization (RR 0.76, 95% CI 0.66 to 0.88, p < 0.001) compared with those treated between 1990 and 1994. Thus, in patients with unstable angina referred for percutaneous revascularization, previous CABG is associated with reduced event-free survival, although the outcome of post-CABG patients treated from 1995 to 1998 is superior to that observed in patients treated from 1990 to 1994. In patients who underwent previous CABG, treatment of native lesions affords better long-term outcome than vein graft intervention.

Influence of coronary thrombus on outcome of percutaneous coronary angioplasty in the current era (the Mayo Clinic experience).

Earlier studies documented an increased risk of percutaneous coronary intervention (PCI) in patients with angiographic evidence of thrombus. With newer antiplatelet agents and stents, it is not known whether thrombus is a risk factor after PCI. This study examines whether outcome of PCI in patients with thrombus has improved, and whether thrombus is associated with adverse outcome after PCI in the current era. This single-institution retrospective analysis of PCI in 7,184 patients was divided into 2 periods: group I, 1990 to 1995 (n = 3,640), and group II, 1996 to 1999 (n = 3,544). The groups were subdivided according to the presence or absence of angiographic thrombus before PCI. We compared the outcome of PCI for patients with and without thrombus in group II. A comparison was made in the 2 groups in patients with angiographic thrombus. Procedural success improved in group II compared with group I patients with thrombus (93% vs 88%, p <0.001). There was significant reduction in abrupt closure in the recent era in patients with thrombus (4% vs 7%, p = 0.01). In group II, procedural success remained lower in patients with (93% vs 96%) than without thrombus (p <0.001). After adjusting for the significant univariate characteristics of group II patients, thrombus remained an independent predictor of Q-wave infarction (odds ratio 3.78; 95% confidence interval [CI], 1.8 to 8.0; p <0.0013) and the composite end point of death, Q-wave infarction, and emergency bypass surgery (odds ratio 2.37; 95% CI 1.4 to 4.1; p = 0.002). There was a trend toward increased in-hospital death among patients with thrombus (odds ratio 2.06; 95% CI 0.9 to 4.8; p = 0.09). The 1-year outcome after successful PCI was similar for those with and without thrombus. Despite improvement in the outcome of patients with thrombus undergoing PCI in recent years, thrombus is still an independent predictor of adverse in-hospital outcomes after PCI.

Brachial plexus anesthesia for outpatient surgical procedures on an upper extremity.

We retrospectively reviewed 543 brachial plexus blocks performed on 526 outpatients. Most (98%) of the blocks were performed by means of the axillary approach. Various techniques were used, including paresthesia, transarterial fixation, nerve stimulation, or a combination of techniques; a high success rate was achieved with each of them. Only 7% of the blocks were incomplete and thus necessitated either general anesthesia or block supplementation with thiopental sodium and nitrous oxide. No persistent neurologic deficit was ascribed to the anesthetic technique. This review indicates that brachial plexus block, especially with use of the axillary approach, is a safe and effective option for outpatient surgical procedures on an upper extremity.

A versatile, computer-controlled, closed-loop system for continuous infusion of muscle relaxants.

A computer-controlled, closed-loop system for continuous infusion of muscle relaxants that allows the operator to choose either atracurium besylate or vecuronium bromide to provide any desired target level of neuromuscular blockade is described. This new system offers certain advantages over computer-controlled systems described previously for continuous infusion of muscle relaxants--that is, the option to choose either of two muscle relaxants to be infused and the inclusion of monitors to provide feedback about the dosage needed to produce a target level of neuromuscular blockade. The clinical performance of this system was tested in 36 patients who were 18 to 65 years old, were classified in American Society of Anesthesiologists physical status 1 or 2, and were undergoing elective orthopedic, abdominal, or thoracic procedures. In all patients, the control algorithm rapidly induced the target level of neuromuscular blockade and maintained that level of blockade at steady state with minimal oscillation. We conclude that the automatic feedback control system described can induce and precisely maintain any predetermined target level of neuromuscular blockade.

Monitoring and analysis of oxygenation and ventilation during rigid bronchoscopic neodymium-YAG laser resection of airway tumors.

Neodymium-YAG (yttrium-aluminum-garnet) laser resection of obstructing and inoperable tumors of the large airways is used as palliative therapy to improve the quality of survival in patients by alleviating airway obstruction. Rapid changes in oxygenation and ventilation can occur during these procedures. In a study of 14 patients, transcutaneous oxygen (PtcO2) and carbon dioxide (PtcCO2) monitors responded slowly to these changes and frequently provided misleading values. Pulse oximetry (SNO2) accurately reflected arterial oxygen saturation but did not indicate severe desaturation until arterial oxygen tension approached dangerously low values. Thus, we did not find PtcO2 or PtcCO2 monitoring to be clinically useful during neodymium-YAG laser resection of airway tumors through a rigid bronchoscope. SNO2 was clinically useful and accurate; however, a large decrement in oxygenation may occur before changes in oxygen saturation ensue and are detected.

Role of preoperative cessation of smoking and other factors in postoperative pulmonary complications: a blinded prospective study of coronary artery bypass patients.

The association between preoperative smoking cessation and postoperative pulmonary morbidity was studied prospectively in 200 consecutive patients undergoing an elective coronary artery bypass surgical procedure. Detailed respiratory, cardiovascular, and smoking histories were elicited. Preoperative arterial blood gas analyses and bedside spirometry were performed. Urinary cotinine levels were measured to verify smoking histories. During spirometry, severe angina developed in seven patients, who were hence excluded from the study; one patient died of hemorrhage intraoperatively. An observer unaware of patients' preoperative histories assessed the remaining 192 patients throughout the intraoperative and postoperative periods for pulmonary complications. Postoperative pulmonary complications occurred in a third of the current smokers. Patients who had stopped smoking for 2 months or less had a pulmonary complication rate almost 4 times that of patients who had stopped for more than 2 months (57.1% versus 14.5%). Patients who had stopped smoking for more than 6 months had rates similar to those who had never smoked (11.1% and 11.9%, respectively). Preoperative pulmonary dysfunction, increased pack-years of smoking, prolonged surgical time, and the use of enflurane were independently associated with postoperative pulmonary morbidity (P less than 0.05). We concluded that smoking cessation should occur at least 2 months preoperatively to maximize the reduction of postoperative respiratory complications.