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Dissection of the left main coronary artery during coronary artery bypass graft (CABG) surgery is a rare, potentially lethal complication, usually diagnosed at post-mortem. During the cross-clamp period of a 4-vessel coronary artery bypass graft procedure in a 74-year old hypertensive woman, retrograde dissection occurred in a diffusely diseased marginal artery when perfused with cardioplegic solution at a pressure of 140-150 mmHg through a vein graft. The dissection extended back to the left main artery, included the posterior proximal ascending aorta and then down the left anterior descending artery (LAD). Transoesophageal echocardiography (TOE) confirmed the left main dissection and showed anterior-septal-lateral akinesis in a previously normally functioning left ventricle (LV). The circumferentially calcified proximal LAD was grafted with a saphenous vein by carving an oval area of calcium creating an elliptical opening in the artery wall. Normal LV function returned and, in the area of the left main dissection, there was only thickening with no colour flow. Eight months postoperatively cardiac catheterization showed normal LV function, patent vein grafts to the right coronary artery and proximal LAD, left internal mammary artery to distal LAD and an occluded sequential marginal vein graft. Twelve years postoperatively, the patient is well with Class I angina, on medication. There is no previous documentation of a diagnosed and successfully treated left main dissection during CABG surgery. Since this case using the technique of creating an oval opening in a circumferentially calcified coronary artery (with an otherwise satisfactory lumen), the author has been using this technique to bypass otherwise non-bypassable arteries; this technique may be useful to help patients with severe calcific coronary artery disease.

OBJECTIVES: Skeletonization of the internal mammary artery (IMA) facilitates arterial grafting and has been shown to reduce deep sternal infection but is more time-consuming and tedious than pedicle harvest. We wished to determine if use of harmonic technology (HT) facilitates skeletonization of the IMA and is as safe as the conventional technique of skeletonization. METHODS: In a consecutive series of 1057 patients with isolated coronary artery bypass graft (CABG) surgery from 2003 to 2013, adverse events and recorded harvest times were compared between harmonic (965 patients) and non-harmonic patients (86 patients). RESULTS: HT was used to harvest 1640 IMAs in 965 (91%) of 1057 consecutive CABG patients and skeletonization with the traditional technique (use of an electrocautery tip as a dissector) was used to harvest 147 IMAs in 86 patients. Six patients had no IMA harvested with this surgery (4 patients had an IMA used from a previous CABG, 1 had no disease of the left anterior descending coronary artery and 1 patient was in cardiogenic shock precluding IMA use). Excluding patients with single-vessel disease, 730/987 (74%) of patients received bilateral IMAs. Demographics of patients with and without harmonic skeletonization, respectively, were the following: mean age: 64.7 vs 67.7 years; diabetes: 33 vs 34%; women: 21 vs 26% and median European System for Cardiac Operative Risk Evaluation: 2.9 vs 3.2. The mean harvest time for 77 non-harmonic skeletonized mammary arteries (49 surgeries) was 32.2 min (95% confidence interval (CI): 30.1, 34.3), for harmonic skeletonized arteries after 450 surgeries was 28.4 min, (95% CI: 27.8, 29.1) and in the last 100 IMAs harvested for the isolated harmonic device use/mammary was 15.4 min (95% CI: 14.0, 16.7). Major adverse events for patients with and without harmonic skeletonization, respectively, were: reoperation for bleeding: 2.7 vs 3.5% (difference = 0.8%, 95% CI: −3.2, 4.8); damaged mammaries: 0.4 vs 0.7% (difference = 0.3%, 95% CI: −1.0, 1.7); deep sternal infection: 1.6 vs 1.2% (difference = −0.4%, 95% CI: −2.8, 2.0) and perioperative infarction: 1.7 vs 2.3% (difference = 0.7%, 95% CI: −2.6, 4.0). CONCLUSION: In this largest series to date of harmonic IMA skeletonization, this technique results in rare damage, is quicker and with a comparable adverse event rate compared with the non-harmonic method.

Since the 1970s the Canadian Prairies have experienced a steady replacement of summer fallow with continuous cropping practices. It has been suggested that such regional scale changes in agricultural land use result in the modification of the regional climate and its variability. Our study explores this influence using linear discriminant analysis (LDA) to determine whether agricultural land use variables can discriminate the classes of exceedance (positive/negative beyond a given small scale variability range) found in the maximum and minimum daily temperature, diurnal temperature range (DTR), daily precipitation and daily incoming solar radiation. These classes of exceedance describe whether the climate was warmer/cooler, drier/wetter and sunnier/cloudier relative to the small scale variability range. The land use data consisted of summer fallow, annuals and perennials for the 127 ecodistricts in the Prairies ecozone. The climate data were neighbouring station data interpolated to the ecodistrict's centroid. Both data sets covered the period 1951–2006 and the analysis covered the entire data period with focus on 1971–2006 that coincided with the decline in summer fallow practice. It considered the primary growing season months of June, July and August and used the winter months of January and February as a contrast. Our approach showed that where large scale changes in agricultural land cover occurs we can establish a statistical relationship between such changes and the modification of the climate's variability. June coincided with the period of maximum positive growth rate and hence land cover change. The greatest discriminating power was therefore found to occur in June for the exceedance classes of maximum and minimum temperature and solar radiation over the 1971–2006 period with success rates ranging from 85 to 93%. The greatest success in discriminating the DTR classes was at 82% in July.

Background The efficacy of coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) in patients with coronary artery disease has been well defined by randomized controlled trials. However, patients with severe left ventricular dysfunction (ejection fraction Methods The Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH), a clinical data collection and outcome monitoring initiative for the province of Alberta, Canada, was used to identify 2925 patients with coronary artery disease and left ventricular dysfunction undergoing CABG (n = 1,326) or PCI (n = 1,599) between 1995 and 2008. Patients were propensity matched to obtain comparable subgroups among left ventricular dysfunction patients. Results Cox proportional hazard analysis of the propensity-matched subgroups identified that CABG was significantly associated with lower rates of repeat revascularization and better survival compared with PCI at 1, 5, 10, and 15 years. Other significant independent predictors of poor long-term survival included age, renal failure, heart failure, diabetes mellitus, peripheral vascular disease, prior myocardial infarction, left main coronary artery disease, and prior CABG. Conclusions For patients with coronary artery disease and left ventricular dysfunction, CABG was associated with lower rates of repeat revascularization and improved survival over PCI, after adjustment for baseline risk profile differences. Further research exploring the factors leading to use of a particular revascularization modality in this patient population is required.

textabstractPurpose of Review: Arterial grafting is superior to venous grafting in coronary artery bypass graft surgery with respect to graft patency and long-term patient outcome, but it may be difficult to achieve complete arterial revascularization. Recent Findings: Use of arterial grafts, especially bilateral internal mammary artery grafts, is not common, whereas there are clear indications that it may increase survival. Definitions of complete revascularization are varied and confusing, making study comparisons difficult. Technical challenges in complete revascularization with arterial grafts can be minimized by surgical techniques. Competitive flow in moderately stenosed coronary arteries grafted with arterial conduits may result in reduced patency. While internal mammary arteries may be used in arteries with at least 60% stenosis, radial artery and gastroepiploic grafts are best placed onto coronaries with severe stenosis. Moderate lesions in the left coronary circulation should be bypassed, but right coronary artery lesions can be left untouched as there is minimal progression over time. Complete revascularization may not be necessary or possible in every patient because of technical challenges. CONCLUSION: Complete revascularization with arterial grafts presents both technical and physiological challenges. However, with techniques to maximize length of arterial conduits, knowledge of competitive flow and which moderate lesions should be addressed, complete revascularization with arterial grafts can be accomplished in the majority of patients, notwithstanding it may not be possible or even indicated for every patient.

In future lead cooled nuclear power systems the heavy liquid-metal pump will be placed in the hot temperature region of the reactor. This combines corrosion problematic at elevated temperatures with erosion at the impeller of the pump. Several steels designed for conventional mechanical high loaded pumps and the SiSiC have been tested in oxygen containing stagnant lead (10 −6 and 10 −8 wt%) at 550 and 600 °C for 2000 and 4000 h in the COSTA-facilities. Only SiSiC shows no influence by the liquid metal. No dissolution attack occurs at cast iron steels but inner oxidation takes place. NORILOY shows no dissolution attack. All other steels are attacked by liquid lead at one of the conditions. To evaluate the erosion–corrosion attack a new test facility allowing velocities of the lead of up to 20 m/s was designed and constructed. With a CFD-code the behaviour and flow velocity of the lead are simulated.

Clinical trials in phase II of drug development are frequently conducted as single-arm two-stage studies with a binary endpoint. Recently, adaptive designs have been proposed for this setting that enable a midcourse modification of the sample size. While these designs are elaborated with respect to hypothesis testing by assuring control of the type I error rate, the topic of point estimation has up to now not been addressed. For adaptive designs with a prespecified sample size recalculation rule, we propose a new point estimator that both assures compatibility of estimation and test decision and minimizes average mean squared error. This estimator can be interpreted as a constrained posterior mean estimate based on the non-informative Jeffreys prior. A comparative investigation of the operating characteristics demonstrates the favorable properties of the proposed approach. Copyright © 2016 John WileySons, Ltd.

OBJECTIVES: The purpose of this study was to compare effectiveness of the 1999 logistic EuroSCORE (LES) and of the 2012 EuroSCORE II (ESII) in a real-world patient population of 1125 patients undergoing total arterial grafting (TAG) coronary artery bypass graft (CABG) surgery. METHODS: The performance of the two risk scores was compared using (i) discrimination (accuracy of discriminating non-survivors from survivors), (ii) calibration (assessment of agreement between the predicted/observed outcomes) and (iii) agreement between the two scores. By averaging medians of LES and ESII and then sub-division into 10 equal groups, actual operative mortality rate was compared with the median LES and ESII within each risk group, the difference plotted against the average risk score (as in a Bland and Altman plot), and using the traditional risk groupings for EuroSCORE of low (0-2.99), medium (3-5.99) and high risk (6.0 and above), the reclassification rate of ESII was compared with that of LES. RESULTS: In 1125 consecutive total arterial CABG patients, demographics included: mean age 64.6 years, 79% males, 35% diabetic patients, 57% urgent/emergent patients, 37% off-pump and 77% bilateral mammary grafting. Overall operative mortality was 3.2% (36 patients). Comparison of the LES and ESII showed (i) good discrimination for both LES and ESII (area under the curve for LES was 0.85 and for ESII was 0.87); (ii) neither score was well calibrated: LES tended to overestimate and ESII underestimated risk. In general, the ESII provided a better estimate of risk in lower risk patients and LES was better for the highest risk group. (iii) In terms of agreement, in the lower four risk groups the risk was overestimated by both scores, in five of the higher six risk groups ESII underestimated risk and LES overestimated risk, and in the highest risk group LES was very close (17.2 cf. 17.7) compared with ESII (5.6 cf. 17.7). In addition, ESII downgraded risk in 96.8% of survivors and in 97.2% of non-survivors. CONCLUSIONS: In 1125 consecutive TAG CABG patients, neither LES nor ESII performed well enough to be used as a consistent risk stratification tool; LES overestimated risk but was highly accurate for the highest of 10 risk groups and ESII consistently underestimated risk in all patients.

Ginkgo biloba special extract EGb 761, an anti-dementia drug, enhances cognitive functioning and stabilizes mood in cognitively impaired elderly subjects. Moreover, EGb 761 had been found to alleviate symptoms of anxiety in people with mental decline, therefore it was now tested for clinical efficacy in younger patients suffering from anxiety. One hundred and seven patients with generalized anxiety disorder (GAD, n=82) or adjustment disorder with anxious mood (ADWAM, n=25) according to the diagnostic and statistical manual of mental disorders, third edition - revised (DSM-III-R) were randomized to daily doses of 480 mg EGb 761, 240 mg EGb 761 or placebo for 4 weeks. Intention-to-treat (ITT) analyses were performed on the primary outcome measure, the Hamilton rating scale for anxiety (HAMA), and the secondary variables, the clinical global impression of change (CGI-C), the Erlangen anxiety tension and aggression scale (EAAS), the list of complaints (B-L'), and the patient's global rating of change. The HAMA total scores decreased by -14.3 (+/-8.1), -12.1 (+/-9.0) and -7.8 (+/-9.2) in the high-dose EGb 761, the low-dose EGb 761 and the placebo group, respectively. Changes were significantly different from placebo for both treatment groups with p=0.0003 (high-dose group) and p=0.01 (low-dose). Regression analyses revealed a dose-response trend (p=0.003). EGb 761 was significantly superior to placebo on all secondary outcome measures. It was safe and well tolerated and may thus be of particular value in elderly patients with anxiety related to cognitive decline.

Background: Remote ischemic preconditioning is a simple therapy that may reduce cardiac and kidney injury. We undertook a randomized controlled trial to evaluate the effect of this therapy on markers of heart and kidney injury after cardiac surgery. Methods: Patients at high risk of death within 30 days after cardiac surgery were randomly assigned to undergo remote ischemic preconditioning or a sham procedure after induction of anesthesia. The preconditioning therapy was three 5-minute cycles of thigh ischemia, with 5 minutes of reperfusion between cycles. The sham procedure was identical except that ischemia was not induced. The primary outcome was peak creatine kinase–myocardial band (CK-MB) within 24 hours after surgery (expressed as multiples of the upper limit of normal, with log transformation). The secondary outcome was change in creatinine level within 4 days after surgery (expressed as log-transformed micromoles per litre). Patient-important outcomes were assessed up to 6 months after randomization. Results: We randomly assigned 128 patients to remote ischemic preconditioning and 130 to the sham therapy. There were no significant differences in postoperative CK-MB (absolute mean difference 0.15, 95% confidence interval [CI] −0.07 to 0.36) or creatinine (absolute mean difference 0.06, 95% CI −0.10 to 0.23). Other outcomes did not differ significantly for remote ischemic preconditioning relative to the sham therapy: for myocardial infarction, relative risk (RR) 1.35 (95% CI 0.85 to 2.17); for acute kidney injury, RR 1.10 (95% CI 0.68 to 1.78); for stroke, RR 1.02 (95% CI 0.34 to 3.07); and for death, RR 1.47 (95% CI 0.65 to 3.31). Interpretation: Remote ischemic precnditioning did not reduce myocardial or kidney injury during cardiac surgery. This type of therapy is unlikely to substantially improve patient-important outcomes in cardiac surgery. Trial registration: ClinicalTrials.gov, no. NCT01071265.

Action of the uppermost medial internal intercostal muscles-the parasternals-during rapid eye movement (REM) is uncertain; no direct recordings exist of shortening of these muscles during sleep. Historically, motor inhibition of skeletal muscles during REM sleep is thought to cause global loss of chest wall muscle function, REM "atonia," with preservation of only diaphragm function. However, recent evidence during wakefulness shows parasternals as distinctive obligatory inspiratory muscles. Therefore we hypothesized that attenuation of chest wall function during sleep may spare the parasternals along with the diaphragm, as essential muscles of inspiration during REM. We studied seven canines, comparing costal and crural diaphragm and parasternal intercostal muscle function during wakefulness and non-REM (NREM) and REM sleep, during normal spontaneous sleep, continuously recording ventilation and simultaneous muscle electromyogram (EMG) and length from sonomicrometry microtransducers. Ventilation during sleep declined significantly from wakefulness. From wakefulness to NREM and REM, costal and crural tidal EMG increased, while parasternal tidal EMG was preserved unchanged. Costal and crural shortening per breath during NREM and REM did not change significantly from wakefulness. Concurrently, parasternal shortening decreased equally in both NREM and REM despite preservation of the parasternal EMG. We conclude that diaphragm and parasternals are not inhibited, and both remain active together as essential inspiratory muscles, during REM sleep. The lesser contraction of parasternal intercostals compared with diaphragm may be attributed to net changes in mechanics affecting the chest wall during sleep.

SC7A1 is a cosmid with an insert of chromosomal DNA from Streptomyces coelicolor A3(2). Its insertion into the chromosome of S. coelicolor strains caused a duplication of a segment of ca. 40 kb and delayed actinorhodin antibiotic production and sporulation, implying that SC7A1 carried a gene negatively affecting these processes. The subcloning of SC7A1 insert DNA resulted in the identification of the open reading frame SCO5582 as nsdA , a gene n egatively affecting S treptomyces d ifferentiation. The disruption of chromosomal nsdA caused the overproduction of spores and of three of four known S. coelicolor antibiotics of quite different chemical types. In at least one case (that of actinorhodin), this was correlated with premature expression of a pathway-specific regulatory gene ( actII-orf4 ), implying that nsdA in the wild-type strain indirectly repressed the expression of the actinorhodin biosynthesis cluster. nsdA expression was up-regulated upon aerial mycelium initiation and was strongest in the aerial mycelium. NsdA has DUF921, a Streptomyces protein domain of unknown function and a conserved SXR site. A site-directed mutation (S458A) in this site in NsdA abolished its function. Blast searching showed that NsdA homologues are present in some Streptomyces genomes. Outside of streptomycetes, NsdA-like proteins have been found in several actinomycetes. The disruption of the nsdA -like gene SCO4114 had no obvious phenotypic effects on S. coelicolor . The nsdA orthologue SAV2652 in S. avermitilis could complement the S. coelicolor nsdA -null mutant phenotype.

Objective Recent research with several synthetic antidepressants indicates that early improvement during the initial weeks of treatment may be a highly sensitive predictor of therapeutic success in major depression. We investigated whether early improvement is sensitive and specific in predicting sustained response and non-response to antidepressant treatment with Hypericum extract WS(R) 5570/5572 and whether the results reported for synthetic antidepressants apply to these Hypericum extracts as well. Methods We analyzed original data of 3 double-blind, randomized trials including a total of 594 adult out-patients suffering from major depression according to DSM-IV criteria, who received well-characterized Hypericum extract preparations WS(R) 5570, WS(R) 5572, WS(R) 5573 or placebo for 6 weeks. The main outcome measure was the prediction of a sustained > or = 50 % decrease of the Hamilton Depression Scale (HAM-D) total score versus baseline ('sustained response') by the presence of > or =20 % HAM-D total score improvement after 1 and 2 weeks of treatment ('early improvement'). Results For Hypericum extract, early improvement had a sensitivity of 87 % (95 % confidence interval [CI], 82-93 %) and a specificity of 54 % (95 % CI, 45-62 %) at day 14, and a sensitivity of 43 % (95 % CI, 35-51 %) and a specificity of 86 % (95 % CI, 80-92 %) at day 7 for predicting sustained response. After 2 weeks of treatment, 78 % (95 % CI, 69-87 %) of the patients who failed to improve did not show sustained response later during treatment. Conclusion A substantial fraction of the patients treated with Hypericum extracts WS(R) 5570/5572 showed a meaningful reduction of depressive symptoms during the first two weeks of treatment (early improvement), which was found to be a sensitive predictor of sustained response. The results determined for the herbal extracts were comparable to those for effective synthetic antidepressants investigated previously.

Summary Objective: Information about adverse drug reactions plays an important role when assessing the benefit/risk profile of a drug. Identifying rare adverse drug reactions, however, is a difficult task. This paper illustrates the advantages of using a prescription database for this purpose. Methods: The mediplus® database used in our analysis covered data from 320,644 outpatients observed between July 1999 and June 2002. The example of bleeding complications during intake of antidementia drugs is used to illustrate this approach. The comparison of cohorts and subgroups is nearly always a problem in surveys. For our analyses we considered a set of patients who had taken a selected medication for a certain period of time and compared the frequency of adverse events with those occurring when the same patients did not take this medication. Hence, the comparison with versus without a certain medication is based on the same set of patients as in a cross-over study. Results: Our evaluations indicate that the rate of bleeding complications is low when taking any of the widely used antidementia drugs, glutamate modulators, cholinesterase inhibitors, calcium antagonists or the phytomedicine Ginkgo biloba. Conclusion: Basing the comparison of the rates of complications during periods with and without intake of a certain drug on the same set of patients may be a useful tool for assessing adverse drug reactions from data reported in prescription databases.

The sequencing of the entire genetic complement of Streptomyces coelicolor A3(2) has been completed with the determination of the 365,023 bp sequence of the linear plasmid SCP1. Remarkably, the functional distribution of SCP1 genes somewhat resembles that of the chromosome: predicted gene products/functions include ECF sigma factors, antibiotic biosynthesis, a gamma-butyrolactone signalling system, members of the actinomycete-specific Wbl class of regulatory proteins and 14 secreted proteins. Some of these genes are among the 18 that contain a TTA codon, making them targets for the developmentally important tRNA encoded by the bldA gene. RNA analysis and gene fusions showed that one of the TTA-containing genes is part of a large bldA-dependent operon, the gene products of which include three proteins isolated from the spore surface by detergent washing (SapC, D and E), and several probable metabolic enzymes. SCP1 shows much evidence of recombinational interactions with other replicons and transposable elements during its history. For example, it has two sets of partitioning genes (which may explain why an integrated copy of SCP1 partially suppressed the defective partitioning of a parAB-deleted chromosome during sporulation). SCP1 carries a cluster of probable transfer determinants and genes encoding likely DNA polymerase III subunits, but it lacks an obvious candidate gene for the terminal protein associated with its ends. This may be related to atypical features of its end sequences.

Rapid body mass loss (RBML) before competition was found to decrease hemoglobin mass (Hbmass ) in elite boxers. This study aimed to investigate the underlying mechanisms of this observation. Fourteen well-trained combat athletes who reduced body mass before competitions (weight loss group, WLG) and 14 combat athletes who did not practice RBML (control group, CON) were tested during an ordinary training period (t-1), 1-2 days before an official competition (after 5-7 days RBML in WLG, t-2), and after a post-competition period (t-3). In WLG, body mass (-5.5%, range: 2.9-6.8 kg) and Hbmass (-4.1%) were significantly (P 0.001) reduced after RBML and were still decreased by 1.6% (P 0.05) and 2.6% (P 0.001) at t-3 compared with t-1. After RBML, erythropoietin, reticulocytes, haptoglobin, triiodothyronine (FT3 ), and free androgen index (FAI) were decreased compared with t-1 and t-3. An increase occurred in ferritin and bilirubin. Peak treadmill-running performance and VO2peak did not change significantly, but performance at 4-mmol lactate threshold was higher after RBML (P 0.05). In CON, no significant changes were found in any parameter. Apparently, the significant decrease in Hbmass after RBML in combat athletes was caused by impaired erythropoiesis and increased hemolysis without significant impact on aerobic performance capacity.

In Nollan v. California Coastal Commission, 483 U.S. 825 (1987), and Dolan v. City of Tigard, 512 U.S. 374 (1994), the Supreme Court held that an agency could not, consistent with the Takings Clause, condition a permit on a land exaction unless the exaction bears an “essential nexus” and “rough proportionality” to the harms the government seeks to mitigate. Then, in Koontz v. St. Johns Water Management District, 133 S. Ct. 2586 (2013), the Court extended Nollan and Dolan to exactions that were never completed because the property owner refused to acquiesce to the demand. Nevertheless, the Court held that such property owners suffer a “constitutionally cognizable injury” under the unconstitutional conditions doctrine because the government has significantly burdened their right not to have property taken without just compensation. Because the case arose under a Florida statute, the Court did not decide what the proper federal remedy would be in these “failed exaction” cases.This Article argues that failed exaction plaintiffs should be entitled to actual damages under the federal civil rights statute, 42 U.S.C. § 1983. Because failed exactions do not involve a completed taking, the Just Compensation Clause is not the proper remedy. But a recognized constitutional injury cannot go uncompensated. Limiting the remedy to invalidation of the offending condition suffers from two faults. First, it fails to provide property owners with adequate compensation. Second, it does not serve as a deterrent to agencies. An invalidation remedy standing alone gives permitting agencies a “do-over” and encourages them to use to permitting process to prevent development through the use of unconstitutional conditions. On the contrary, a damages remedy is supported by Section 1983 and serves the twin aims of deterrence and compensation. Courts should hold that property owners bringing a failed exaction claim under Koontz are entitled to their actual economic damages.Along with that federal damages remedy, the Article argues that these plaintiffs should be able to bring their claims directly in federal court. Because failed exaction plaintiffs have not suffered a taking, they cannot seek Just Compensation. Therefore, the ripeness rule for federal takings claims established in Williamson County Regional Planning Commission v. Hamilton Bank, 473 U.S. 185 (1985), which generally requires property owners to seek just compensation in state court to “ripen” a takings claim, does not apply to failed exactions. Property owners suing under a Koontz theory should be able to assert their federal constitutional rights directly in federal court.

Hybrids of the Streptomyces coelicolor conjugative plasmid SCP2* and the Mycobacterium plasmid pAL5000 were transferred from Streptomyces coelicolor or Streptomyces lividans to Mycobacterium smegmatis mc2155 in plate crosses. Inactivation of the SCP2* transfer function did not prevent or reduce plasmid transfer. This transfer was DNase I sensitive and thus involved release of DNA from Streptomyces, followed by transformation of M. smegmatis. M. smegmatis growing on specific solid media was also transformed by pure CCC and linear plasmid DNA. Small plasmids were taken up intact but large plasmids suffered deletions. Competence developed within 24 h of incubation at 30 degrees C or 37 degrees C, and up to 400 transformants were obtained per microg of CCC plasmid DNA. Transformation frequencies were higher when M. smegmatis was co-cultivated with plasmid-free Streptomyces, but unaffected by resident homologous sequences or inactivation of recA in M. smegmatis. Spontaneous transformation was also observed with a circular Streptomyces transposable element which inserted into chromosomal sites. Transformative plasmid transfer was also shown to occur between M. smegmatis strains. This is the first report of non-artificially induced, spontaneous plasmid transformation in Mycobacterium.

Genetic mapping of the chromosome of Streptomyces coelicolor A3(2) began with the analysis of haploid recombinants selected from matings. A physical map of the S. coelicolor chromosome has recently been constructed, using pulsed-field gel electrophoresis of AseI and DraI fragments. The genetic map was found to be reasonably congruent with the physical map over the well-marked quadrants. It was also apparent that the silent regions are indeed long stretches of DNA. It certainly appears at present that wild-type streptomycetes carry considerable stretches of DNA that presumably has selective value in natural habitats-otherwise it would not have persisted-but has only subtle effects on phenotype when deleted in laboratory variants. The arrangement of genes in the well-marked segments seems to be extensively conserved even between streptomycetes that are not very closely related, as in the well-known case of E. coli K-12 and S. typhimurium LT2, or in pseudomonads, which show extensive map similarities for groups of genes of primary metabolism but not for segments determining specialized functions peculiar to individual species.

A 5-week randomized, placebo-controlled, double-blind study was carried out to investigate the efficacy of kava-kava special extract WS®1490 in non-psychotic nervous anxiety, tension and restlessness states. During the first treatment week, the study dose drug was increased from 50 mg to 300 mg per day and pretreatment with benzodiazepines was tapered off over 2 weeks. These dosage adjustments were followed by 3 weeks of monotherapy with WS®1490 or placebo. Outcome measures were the differences between baseline and end of treatment on the Hamilton Anxiety Scale (HAMA) and on a subjective well-being scale (Bf-S), as well as the benzodiazepine withdrawal symptoms. Changes in the Erlanger Anxiety, Tension and Aggression Scale (EAAS) and Clinical Global Impressions (CGI) were analyzed as secondary measures. Treatment safety was checked by interviews, adverse event reports and laboratory investigations. Forty patients (2×20) were included into the study. WS®1490 was superior to placebo regarding the HAMA (P=0.01) and Bf-S (P=0.002) total scores and all secondary efficacy measures. The tolerance of WS®1490 was not inferior to placebo. The study confirms the anxiolytic efficacy and good tolerance of WS®1490 and shows that a further symptom reduction is possible after a change-over from benzodiazepine treatment.

Objective: Endothelial dysfunction, specifically endothelium-derived contracting factors have been implicated in the development of arterial conduit vasospasm. The potent vasoconstrictor endothelin-1 (ET-1) has received much attention in this regard. The present study was designed to evaluate the role of ET-1 in the development of endothelial dysfunction in human internal mammary arteries (IMA). To this aim, we examined the effects of specific and non-specific ET-receptor antagonists on endothelial function (assessed using acetylcholine (ACh)-induced vasodilation) in segments of IMA obtained during coronary artery bypass graft (CABG) surgery. Methods: Vascular segments of IMA were obtained from 51 patients undergoing elective coronary artery bypass graft (CABG) surgery and in vitro endothelium-dependent and -independent responses to ACh and sodium nitroprusside (SNP) were assessed. Isometric dose response curves (DRC) to ACh and SNP were constructed in pre-contracted rings in the presence and absence of bosentan (ETA/B receptor antagonist, 3 μM), BQ-123 (ETA antagonist, 1 μM) and BQ-788 (ETB antagonist, 1 μM) using the isolated organ bath apparatus. Percent maximum relaxation (% E max) and sensitivity (pEC50) were compared between interventions. Results: ACh caused dose-dependent endothelium-mediated relaxation in IMA (% E max 43±4, pEC50 6.74±0.12). In the presence of bosentan, BQ-123 and BQ-788 ACh-induced relaxation was significantly augmented (% E max bosentan 60±3, BQ-123 56±4, BQ-788 53±5 vs. control 43±4, P 0.05). Conclusions: These data uncover, for the first time, beneficial effects of ET receptor blockade on endothelial-dependent vasorelaxation in human IMA.

A region of the Streptomyces coelicolor A3(2) chromosome was identified and cloned by using as a probe the lipase gene from Streptomyces exfoliatus M11. The cloned region consisted of 6286 bp, and carried a complete lipase gene, lipA, as well as a gene encoding a transcriptional activator (lipR). The S. coelicolor A3(2) lipA gene encodes a functional extracellular lipase 82% identical to the S. exfoliatus M11 lipase; the partially purified S. coelicolor enzyme showed a preference for substrates of short to medium chain length. Transcription of lipA was completely dependent on the presence of lipR, and occurred from a single promoter similar to the lipA promoters of S. exfoliatus M11 and Streptomyces albus G. These three Streptomyces lipA promoters have well-conserved −10 and −35 regions, as well as additional conserved sequences upstream of the −35 region, which could function as targets for transcriptional activation by the cognate LipR regulators. The Streptomyces LipR activators are related to other bacterial regulators of a similar size, constituting a previously unidentified family of proteins that includes MalT, AcoK, AlkS, AfsR, five mycobacterial proteins of unknown function and some Streptomyces regulators in antibiotic synthesis clusters. A lipase-deficient strain of S. coelicolor was constructed and found to be slightly affected in production of the polyketide antibiotic actinorhodin.

In a randomized, double-blind, placebo-controlled, multicenter study, the clinical efficacy and safety of two different extracts of St. John's wort were investigated in 147 male and female out-patients suffering from mild or moderate depression according to DSM-IV criteria. Fifty-six (38.1%) of them had an initial total score ≥ 22 points on the Hamilton Rating Scale for Depression (HAMD, 17-item version). Following a placebo run-in period of three to seven days, the patients were randomized to one of three treatment groups: During the 42-day treatment period, they received 3×1 tablet of either placebo, Hypericum extract WS 5573 (300mg, with a content of 0.5% hyperforin), or Hypericum extract WS 5572 (300 mg, with a content of 5% hyperforin). The manufacturing process for both Hypericum preparations was identical, they only differed with regard to their content of hyperforin. Efficacy regarding depressive symptoms was assessed on days 0, 7,14,28, and 42. The last observation of patients withdrawn from the trial prematurely was carried forward. At the end of the treatment period (day 42), the patients receiving WS 5572 (5% hyperforin) exhibited the largest HAMD reduction versus day 0 (10.3 ± 4.6 points; mean ± SD), followed by the WS 5573 group (0.5% hyperforin; HAMD reduction 8.5 ± 6.1 points) and the placebo group (7.9 ± 5.2 points). The monotonie trend was significant (Jonckheere-Terpstra test; p = 0.017). In patients with an initial HAMD total score ≥ 22, the HAMD reduction was even by 16.5% larger than in the total study group receiving WS 5572. More severely depressed patients treated with WS 5573, however, showed a 22.4% lower reduction of the HAMD total score than the entire WS 5573 treatment group. In patients with HAMD ≥ 22, WS 5572 showed a 53.8% larger HAMD reduction than placebo, whereas WS 5573 was not relevantly different from the placebo level. The mean HAMD reductions, treatment end versus baseline, for the more severely depressed patients were 12.0 (3.7) points, 6.6 (7.7) points and 7.8 (5.4) points [mean (SD)] for WS 5S72, WS 5573 and placebo, respectively. The results of a responder analysis support these findings. The data point to a dose-response relationship between the antidepressant efficacy of Hypericum extract and its hyperforin content. The extract with a higher content of hyperforin was particularly effective in patients who were more severely depressed.

In a randomized, double-blind, placebo-controlled, multicenter study, the clinical efficacy and safety of two different extracts of St. John's wort were investigated in 147 male and female outpatients suffering from mild or moderate depression according to DSM-IV criteria. Following a placebo run-in period of three to seven days, the patients were randomized to one of three treatment groups: During the 42-day treatment period, they received 3 x 1 tablets of either placebo, Hypericum extract WS 5573 (300 mg, with a content of 0.5% hyperforin), or Hypericum extract WS 5572 (300 mg, with a content of 5% hyperforin). The manufacturing process for the two Hypericum preparations was identical, so that they differed only in their hyperforin content. Efficacy regarding depressive symptoms was assessed on days 0, 7, 14, 28, and 42, using the Hamilton Rating Scale for Depression (HAMD, 17-item version) and the Depression Self-Rating Scale (D-S) according to von Zerssen. In addition, the severity of illness was also rated by the investigators on days 0 and 42 using the Clinical Global Impression (CGI) scale. The last observation of patients withdrawn from the trial prematurely was carried forward. At the end of the treatment period (day 42), the patients receiving WS 5572 (5% hyperforin) exhibited the largest HAMD reduction versus day 0 (10.3 +/- 4.6 points; mean +/- SD), followed by the WS 5573 group (0.5% hyperforin; HAMD reduction 8.5 +/- 6.1 points) and the placebo group (7.9 +/- 5.2 points). As regards the change in the HAMD total score between day 0 and treatment end and its relationship to the hyperforin dose, a significant monotonic trend was demonstrated in the Jonckheere-Terpstra test (p = 0.017). In pairwise comparisons, WS 5572 (5% hyperforin) was superior to placebo in alleviating depressive symptoms according to HAMD reduction (Mann-Whitney U-test: p = 0.004), whereas the clinical effects of WS 5573 (0.5% hyperforin) and placebo were descriptively comparable. These results show that the therapeutic effect of St. John's Wort in mild to moderate depression depends on its hyperforin content.

Pulmonary complications after upper abdominal surgery are usually ascribed to temporary postoperative impairment of diaphragm function, which may not originate from intrinsic, structural injury but from reflex inhibition of diaphragm contractility. Spontaneous breathing is interrupted periodically by sighs, even after upper abdominal surgery. If postoperative dysfunction of the diaphragm arises from a reflexic inhibition, then the sigh should temporarily override the inhibition and restore normal diaphragm function. We implanted sonomicrometer and electromyogram transducers chronically in six dogs by laparotomy, then directly measured length, shortening, and electromyogram activity of costal and crural diaphragm segments, parasternal intercostal, and transversus abdominis muscles an average of 8.7 (range, 1-16) d later during resting tidal breathing and sighs. In each animal we analyzed a sequence of breaths, including a sigh, when costal or crural diaphragm contractility was abnormal. With each sigh, the shape and amplitude of costal and crural diaphragm segmental shortening improved abruptly, from 0.9 and 1.4% of baseline length (% LBL) during resting breathing to 12.1 and 11.1% LBL, respectively, during sighs. The sighs were compared to CO2-stimulated breaths of equivalent tidal volume, which did not show either pattern or amplitude of shortening equivalent to sighs. We conclude that diaphragm dysfunction after laparotomy arises from a reflex inhibition, which is overridden abruptly to return diaphragm function briefly to normal during each spontaneous sigh.

Seven DNA fragments containing putative protein serine/threonine kinase genes were cloned from Streptomyces coelicolor A3(2) by hybridization with a 165-bp amplified polymerase chain reaction product of pkaB containing kinase subdomains VI, VII and VIII. Among them, the nucleotide sequences of three fragments containing subdomains VI, VII and VIII were identical, while those of one fragment were identical with that of afsK, another protein serine/threonine kinase gene. However, these kinase-like genes with very similar nucleotide sequences were distributed on the chromosome of S. coelicolor A3(2).

Summary: Putative peptide-synthetase-encoding DNA fragments were isolated from the Streptomyces coelicolor A3(2) chromosome using a PCR-based approach and mapped to a single ∼ 35 kb segment. In integrative transformation experiments, DNA fragments from this region disrupted production of the calcium-dependent antibiotic (CDA) and had sequences characteristic of non-ribosomal peptide synthetases, thus proving that the cda locus had been cloned.

We tested the hypotheses that a dual-chamber pacemaker that paces when intrinsic rate drops abruptly would reduce the number of syncopal spells and improve the quality of life in patients with highly recurrent neurally mediated syncope. Twelve patients with highly frequent neurally mediated syncope and at least 1 syncopal spell after tilt testing received dual-chamber pacemakers with automatic rate-drop sensing. The pacemakers were implanted 17+/-26 months after tilt testing, and the patients then were followed for 12+/-2 months. We compared the time to the first recurrence of syncope, syncope frequency, and quality of life for the 2 periods between tilt testing and pacemaker implantation, and between implantation and last follow-up. Only 6 of 12 patients fainted after pacemaker insertion. The median time to syncope recurrence before and after pacing was 7 days and 5.3 months, respectively. The geometric mean frequency of faints before and after pacing was 5.0 spells/month (95% confidence interval 2.7 to 9.2) and 0.30 spells/month (95% confidence interval 0.2 to 0.4), p0.001. After 6 months the mean perception of health on the 100-point EuroQol scale rose from 55 to 82 (p = 0.003), and the general health perception on the SF-36 scale rose from 51 to 72 (p = 0.005). Permanent dual-chamber pacing with automatic rate-drop sensing in patients with highly frequent syncope is associated with a marked reduction in the likelihood of syncope and a marked improvement in quality of life.

The PREFERE study is a multicenter randomized study of patients with low or early intermediate risk for prostatic cancer. The four treatment options, radical prostatectomy, percutaneous irradiation therapy, permanent seed implantation and active surveillance recommended by the German S3 guidelines and international guidelines will be tested and compared with respect to effectiveness and potential side effects. Over a period of 4 years a total of 7,600 patients are to be recruited and assigned to 1 of these 4 therapy forms according to personal preference (by possible exclusion of 1 or 2 therapy options) in a 2-4 arm study design by randomization.

In March 1994, a health care conference was held in Edmonton, Alberta, at which the values of conference participants towards health care were systematically recorded and analysed. This exploration is significant because the values that underpin the structure of the current publicly-funded and administered Canadian health care system rarely enter current discussions regarding health care system reform. Rather, economic and other sociopolitical forces now seem to be having a major impact on plans and actual changes within the health care system. Thus, the underlying attitudes and beliefs of Canadians towards health care have not been articulated or given due credence. The conference par ticipants identified three dominant values: (1) the dignity of the human person as an indi vidual and social being; (2) respect for pluralism and difference; and (3) accountability These values were found to be robust, in that they sustain a focus on the 'common good'. The common good is the core of the Canadian health care system, and is enshrined in the 1984 Canada Health Act. Conceptually, these values could also lead to significant changes in health care, in keeping with the common good, particularly those changes focusing on the current deficiencies of the Canadian health care system.

Since first introduced in the mid-1960s, coronary artery bypass grafting (CABG) has become the standard of care for patients with coronary artery disease. Surprisingly, the fundamental surgical technique itself did not change much over time. Nevertheless, outcomes after CABG have dramatically improved over the first 50 years. Randomized trials comparing percutaneous coronary intervention (PCI) to CABG have shown converging outcomes for select patient populations, providing more evidence for wider use of PCI. It is increasingly important to focus on the optimization of the short- and long-term outcomes of CABG and to reduce the level of invasiveness of this procedure. This review provides an overview on how new techniques and widespread consideration of evolving strategies have the potential to optimize outcomes after CABG. Such developments include off-pump CABG, clampless/anaortic CABG, minimally invasive CABG with or without extending to hybrid procedures, arterial revascularization, endoscopic vein harvesting, intraprocedural epiaortic scanning, graft flow assessment, and improved secondary prevention measures. In addition, this review represents a framework for future studies by summarizing the areas that need more rigorous clinical (randomized) evaluation.

OBJECTIVES: The management strategy remains controversial for patients presenting with type A acute aortic dissection with cerebrovascular accident or coma. The present study aimed to help guide surgeons treating these high-risk patients. METHODS: Of 1873 patients with type A acute aortic dissection enrolled in the International Registry for Acute Dissection, 87 (4.7%) presented with cerebrovascular accident and 54 (2.9%) with coma. The hospital and 5-year results were stratified by the presence and type of brain injury (no injury vs stroke vs coma) and management type (medical vs surgical). Independent predictors of short- and mid-term survival were identified. RESULTS: Presentation with shock, hypotension, or tamponade (46.8% vs 25.2%; P < .001) and arch vessel involvement (55.0% vs 36.1%; P < .001) was more likely in patients with brain injury. Surgical management was avoided more often in patients with coma (33.3%) or cerebrovascular accident (24.1%) than in those without brain injury (11.1%; P < .001). The overall hospital mortality was 22.7% without brain injury, 40.2% with cerebrovascular accident, and 63.0% with coma (P < .001). Mortality varied among the management types for both cerebrovascular accident (76.2% medical vs 27.0% surgical; P < .001) and coma (100% medical vs 44.4% surgical; P < .001). Postoperatively, cerebrovascular accident and coma resolved in 84.3% and 78.8% of cases, respectively. On logistic regression analysis, surgery was protective against mortality in patients presenting with brain injury (odds ratio 0.058; P < .001). The 5-year survival of patients presenting with cerebrovascular accident and coma was 23.8% and 0% after medical management versus 67.1% and 57.1% after surgery (log rank, P < .001), respectively. CONCLUSIONS: Brain injury at presentation adversely affects hospital survival of patients with type A acute aortic dissection. In the present observational study, the patients selected to undergo surgery demonstrated improved late survival and frequent reversal of neurologic deficits.

We thank Collins and Le Manach for their insightful comments on our paper and also for drawing our attention to their article on sample sizes for external validation of prognostic models, which unfortunately was unavailable when our data were analysed. However, their article examined the effect of sample size for proportional hazards models and we used a logistic regression model (with previously published papers more applicable to the assessment of appropriate sample size).

BACKGROUND To determine the transmural pressure-dimension relations of the right atrium (RA) and right ventricle (RV) before and after pericardiectomy, six open-chest dogs were instrumented with pericardial balloons placed over the RA and RV free walls. METHODS AND RESULTS PA appendage dimensions and RV free-wall segment lengths were measured using sonomicrometry. Intact-pericardium RA and RV transmural pressures were calculated by subtracting the pericardial pressures (measured using balloons) from the cavitary pressures. Pooled data from six animals with pericardium intact indicate that at RA and RV cavitary pressures of 5, 10, and 15 mm Hg, RV pericardial pressure was 4.3 +/- 0.3, 8.6 +/- 1.0, and 13.3 +/- 1.5 mm Hg, respectively, and RA pericardial pressure was 4.8 +/- 0.3, 9.6 +/- 0.6, and 14.6 +/- 0.6 mm Hg, respectively (mean +/- SD). With calculated unstressed dimensions, the cavity dimension data were normalized to strain (in percent). We determined that in the dog, RV strain would increase by 14% and RA by 68% to maintain cavitary pressure at 10 mm Hg on pericardiectomy. To compare these results with clinical data, RV (n = 7) and RA (n = 6) transmural pressures were measured using balloons in patients (age, 19 to 76 years) undergoing cardiac surgery. RA transmural pressure of six patients was 1.0 +/- 1.5 mm Hg when central venous pressures (CVPs) ranged from 3 to 16 mm Hg. RV transmural pressure equaled 1.2 +/- 1.9, 2.3 +/- 1.9, and 3.4 +/- 2.0 mm Hg when CVP was 5, 10, and 15 mm Hg, respectively. CONCLUSIONS Pericardial constraint (as evaluated by the ratio of pericardial to intracavitary pressures when CVP is 10 mm Hg) accounted for 96% of RA cavitary pressure in the dog and 89% in humans and at least 86% of RV cavitary pressure in the dog and 77% in humans.

In humans and some animals, the surviving respiratory muscles are able to compensate fully for unilateral, and partially for bilateral, hemidiaphragm paralysis. To examine differential activity of individual respiratory muscles after unilateral or bilateral diaphragm paralysis, length and electromyogram (EMG) of left costal and crural diaphragm segments, parasternal intercostal, and transversus abdominis were measured directly in five awake canines after implantation with sonomicrometry transducers and bipolar EMG electrodes under three conditions: during normal breathing (NOFRZ), after infusion of local anesthetic (bupivacaine) through a cervical phrenic nerve cuff to induce reversible contralateral hemidiaphragm (CNFRZ), and after bilateral diaphragm (BIFRZ) paralysis. From NOFRZ to CNFRZ, costal, crural, parasternal, and transversus abdominis increased shortening and EMG activity to compensate for contralateral diaphragm paralysis, but the increase in activity was not equivalent for each muscle. With BIFRZ, parasternal and transversus abdominis showed further increases in activity, coordinated between both inspiration and expiration. Normalized intrabreath profiles revealed dynamic differences in development of muscle activity within each breath as paralysis worsened. Review of simultaneous muscle activities showed coordinated interactions among the compensating muscles: passive shortening of transversus, and lengthening of costal and crural, coincided with increased active inspiratory shortening of parasternal. We conclude that an integrated strategy of respiratory muscle compensation for unilateral or bilateral diaphragm paralysis occurs among chest wall, abdominal, and diaphragm segmental muscles, with relative contributions of individual muscles adjusted according to the degree of diaphragm dysfunction.

Three closely linked Streptomyces lividans tRNA genes encoding two tRNA(Lys)s and a tRNA(Gly) were cloned and sequences. The structure of tRNA(Gly) is unusual for eubacterial tRNAs. Including those in previous reports (R. Sedlmeier and H. Schmieger, Nucleic Acids Res. 18:4027, 1990, and R. Sedlmeier, G. Linti, K. Gregor, and H. Schmieger, Gene 132:125-130, 1993), 18 S. lividans tRNA genes were physically mapped on the chromosome of the closely related strain Streptomyces coelicolor A3(2). The structure and organization of tRNA genes of S. lividans and S. coelicolor are compared with those of Escherichia coli and Bacillus subtilis.

Emesis requires a coordinated differential recruitment of gastrointestinal smooth muscle, upper airway muscles, and several muscles involved in respiration. In seven awake intact canines we measured the electrical activity (electromyogram) and shortening of costal and crural diaphragm segments, parasternal intercostal, and transversus abdominis during emesis that was induced by instillation of apomorphine into the lower conjunctival fornix. The process of emesis was tightly coordinated with ventilation and showed four respiratory phases: baseline ventilation (Base), initial preemetic hyperventilation (Hyperv), prodromal ventilation associated with salivation and probable nausea (Prodrome), and finally retching and expulsion (Expel) of gastric contents. Ventilation was suppressed during expulsive events, but a small inspiratory airflow was interjected between expulsions. Resting electromyogram of all four muscles increased during the process of emesis, with costal and crural segments showing a marked decrease in resting length through Prodrome and Expel. To produce an expulsive maneuver, both inspiratory and expiratory muscles were activated synchronously, unlike their usual sequential activation during ventilation, with costal and crural segments and transversus abdominis showing the most shortening. The crural segment showed a biphasic length change with initial shortening and then lengthening to assist esophageal sphincter function during Expel. These results indicate a strong coordinated interaction between brain stem centers responsible for control of respiration and of emesis.

The linearity of the chromosome has been observed in several Streptomyces species, and thus may be characteristic of the genus. The termini of the chromosomes contain inverted repeats, and carry covalently-bound proteins at the 5’ end, presumably the primer for replication. The terminal inverted repeats of the Streptomyces lividans chromosome are about 30 kb long, of which the extreme 16 kb is indistinguishable from that of the right end of the 50-kb linear plasmid SLP2. The terminal sequence of S. lividans exhibits abundant palindromes, resembling those of several linear Streptomyces plasmids for the first 12∼17 bp. In spite of this, the terminal DNA sequences among different species are not highly conserved over long distances.A functional oriC has been located at the center of the chromosomes of Streptomyces coelicolor and S. lividans. These chromosomes appear to replicate bi-directionally from the center and are presumably patched up at the ends by protein-primed replication. At least in S. lividans, the telomeres are dispensable and the chromosome could be circularized in viable cells by targeted recombination, which removed the telomeres and joined the two arms. The circularized chromosomes were unstable, undergoing further rearrangements, and resulted in relatively poor growth and sporulation.Long stretches of DNA on various Streptomyces chromosomes are prone to spontaneous deletions and amplifications. In S. lividans and S. coelicolor, the unstable regions correspond to the termini. Moreover, circularized chromosomes, containing deletions of several hundreds of kb in the terminal regions, were found in some spontaneous deletion mutants of S. lividans ZX7. These observations indicate the readiness of the linear chromosome to be circularized, and implicate the termini in the structural instability of Streptomyces chromosomes.

Background We previously established a proof-of-concept in a human cadaveric model where conventional wire cerclage was augmented with a novel biocompatible bone adhesive that increased mechanical strength and early bone stability. We report the results of a single-center, pilot, randomized clinical trial of the effects of adhesive-enhanced closure of the sternum on functional postoperative recovery. Methods In 55 patients undergoing primary sternotomy, 26 patients underwent conventional wire closure and were compared with 29 patients who underwent adhesive-enhanced closure, which consisted of Kryptonite biocompatible adhesive (Doctors Research Group Inc, Southbury, CT) applied to each sternal edge in addition to conventional 7-wire cerclage. Patients were monitored postoperatively at 72 hours, weekly for 12 weeks, and then after 12 months for incisional pain, analgesic use, and maximal inspiratory capacity measured by spirometry. Standardized assessment tools measured postoperative physical disability and health-related quality of life. Results No adverse events or sternal complications from the adhesive were observed early or after 12 months. Incisional pain and narcotic analgesic use were reduced in adhesive-enhanced closure patients. Inspiratory capacity was significantly improved, postoperative health-related quality of life scores normalized more rapidly, and physical disability scores were reduced. Computed tomography imaging was suggestive of sternal healing. Conclusions Adhesive-enhanced closure is a safe and simple addition to conventional wire closure, with demonstrated benefits on functional recovery, respiratory capacity, incisional pain, and analgesic requirements. A large, multicenter, randomized controlled trial to examine the potential of the adhesive to prevent major sternal complications in higher risk patients is warranted.