Comparison of alternate preparative techniques on wall thickness in coronary artery bypass grafts: The HArVeST randomized controlled trial.

BACKGROUND: The success of coronary artery bypass grafting surgery (CABG) is dependent on long-term graft patency, which is negatively related to early wall thickening. Avoiding high-pressure distension testing for leaks and preserving the surrounding pedicle of fat and adventitia during vein harvesting may reduce wall thickening. METHODS: A single-centre, factorial randomized controlled trial was carried out to compare the impact of testing for leaks under high versus low pressure and harvesting the vein with versus without the pedicle in patients undergoing CABG. The primary outcomes were graft wall thickness, as indicator of medial-intimal hyperplasia, and lumen diameter assessed using intravascular ultrasound after 12 months. RESULTS: Ninety-six eligible participants were recruited. With conventional harvest, low-pressure testing tended to yield a thinner vessel wall compared with high-pressure (mean difference [MD; low minus high] -0.059 mm, 95% confidence interval (CI) -0.12, +0.0039, p = .066). With high pressure testing, veins harvested with the pedicle fat tended to have a thinner vessel wall than those harvested conventionally (MD [pedicle minus conventional] -0.057 mm, 95% CI: -0.12, +0.0037, p = .066, test for interaction p = .07). Lumen diameter was similar across groups (harvest comparison p = .81; pressure comparison p = .24). Low-pressure testing was associated with fewer hospital admissions in the 12 months following surgery (p = .0008). Harvesting the vein with the pedicle fat was associated with more complications during the index admission (p = .0041). CONCLUSIONS: Conventional saphenous vein graft preparation with low-pressure distension and harvesting the vein with a surrounding pedicle yielded similar graft wall thickness after 12 months, but low pressure was associated with fewer adverse events.

Preoperative VolumE Replacement therapy in DIabetic patients undergoing coronary artery bypass grafting surgery: results from an open parallel group randomized Controlled Trial (VeRDiCT).

OBJECTIVES: To investigate the effect of preoperative volume replacement therapy (VRT) on renal function, health outcome and time to fitness for discharge in diabetic patients undergoing coronary artery bypass grafting (CABG). METHODS: In 2 parallel randomized controlled trials, diabetic patients were allocated to preoperative VRT (1 ml/kg/h of Hartmann's solution for 12 h) or usual care. Primary outcome was time to fitness for discharge. Secondary outcomes included acute kidney injury, postoperative complications, patient-reported quality of life (QoL), hospital resource use and markers of renal, cardiac and inflammatory injury. RESULTS: In total, 169 patients were randomized (84 VRT, 85 usual care; mean age 64 years; 88% male). Time to fitness for discharge was similar between groups [median 6 days; interquartile range 5.0-9.0 in both groups; hazard ratio 0.95, 95% confidence interval (CI) 0.65-1.38; P = 0.78]. Postoperative acute kidney injury was not statistically different (VRT: 27.7% vs usual care: 18.8%, odds ratio 1.72, 95% CI 0.82-3.59; P = 0.15). Estimated glomerular filtration rate (mean difference -0.92, 95% CI -4.18 to 2.25; P = 0.56), microalbumin/creatinine ratio [geometric mean ratio (GMR) 1.16, 95% CI 0.94-1.42; P = 0.16], N-acetyl-beta-d-glucosaminidase (GMR 1.08, 95% CI 0.83-1.40; P = 0.57), C-reactive protein (GMR 1.00, 95% CI 0.88-1.13; P = 0.94), troponin T (Trop-T; GMR 1.18, 95% CI 0.78-1.79; P = 0.39) and other secondary health outcomes were similar between groups. QoL improved in both groups at 3 months with no difference observed. CONCLUSIONS: The use of preoperative VRT is not superior to usual care in diabetic patients undergoing CABG. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN02159606.

The Effects of Preoperative Volume Replacement in Diabetic Patients Undergoing Coronary Artery Bypass Grafting Surgery: Protocol for a Randomized Controlled Trial (VeRDiCT Trial).

BACKGROUND: Diabetes mellitus is a major risk factor for prolonged hospital stays, renal failure, and mortality in patients having coronary artery bypass grafting (CABG). Complications pose a serious threat to patients and prolong intensive care and hospital stays. Low glomerular filtration rate (GFR) due to existing renal impairment or volume depletion may exacerbate acute renal impairment/failure in these patients. Preoperative volume replacement therapy (VRT) is reported to increase the GFR and we hypothesize that VRT will reduce renal impairment and related complications in diabetic patients. OBJECTIVE: The objective of this study is to establish the efficacy of preoperative VRT in reducing postoperative complications in diabetic patients undergoing CABG surgery. Time to "fit for discharge", incidence of postoperative renal failure, cardiac injury, inflammation, and other health outcomes will be investigated. METHODS: In this open parallel group randomized controlled trial, 170 diabetic patients undergoing elective or urgent CABG surgery received 1 mL/kg/hour of Hartmann's solution for 12 consecutive hours prior to surgery, versus routine care. The primary outcome was time until participants were "fit for discharge", which is defined as presence of: normal temperature, pulse, and respiration; normal oxygen saturation on air; normal bowel function; and physical mobility. Secondary outcomes included: incidence of renal failure; markers of renal function, inflammation, and cardiac damage; operative morbidity; intensive care stay; patient-assessed outcome, including the Coronary Revascularization Outcome Questionnaire; and use of hospital resources. RESULTS: Recruitment started in July 2010. Enrolment for the study was completed in July 2014. Data analysis commenced in December 2016. Study results will be submitted for publication in the summer of 2017. CONCLUSIONS: VRT is a relatively easy treatment to administer in patients undergoing surgical procedures who are at risk of renal failure. This experimental protocol will increase scientific and clinical knowledge of VRT in diabetic patients undergoing elective or urgent CABG surgery. Findings supporting the efficacy of this intervention could easily be implemented in the health care system. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 02159606; http://www.controlled-trials.com/ISRCTN02159606 (Archived by WebCite at http://www.webcitation.org/6rDkSSkkK).

Registration of Zak ERA8 Soft White Spring Wheat Germplasm with Enhanced Response to ABA and Increased Seed Dormancy.

Zak ERA8 (ENHANCED RESPONSE to ABA8) (Reg. No. GP-966, PI 669443) is a unique line derived from soft white spring wheat (Triticum aestivum L.) cultivar Zak that has increased seed dormancy but after-ripens within 10 to 16 wk. The goal in developing this germplasm was to use increased seed dormancy to improve tolerance to preharvest sprouting, a problem that can cause severe economic losses. This germplasm was developed by USDA-ARS, Pullman, WA, in collaboration with Washington State University. Zak ERA8was tested under experimental number 60.1.27.10. The ERA8mutation was generated by chemical mutagenesis followed by selection for the inability to germinate on abscisic acid (ABA) concentrations too low to inhibit wild-type Zak seed germination. The semidominant Zak ERA8 line has been backcrossed twice to wild-type Zak. Following the first backcross, Zak ERA8 showed similar morphological and grain quality traits to the original Zak cultivar.

PHOTOCHEMICAL REACTION OF NITRO-POLYCYCLIC AROMATIC HYDROCARBONS: EFFECT BY SOLVENT AND STRUCTURE.

Photochemical degradation of 1-nitropyrene, 2-nitrofluorene, 2,7-dinitrofluorene, 6-nitrochrysene, 3-nitrofluoranthene, 5-nitroacenaphthene, and 9-nitroanthracene were examined in CHCl(3), CH(2)Cl(2), DMF, DMF/H(2)O (80/20), CH(3)CN, or CH(3)CN/H(2)O (80/20). The degradation follows mostly the 1(st) order kinetics; but a few follow 2(nd) order kinetics or undergo self-catalysis. The photodegradation rates follow the order: CHCl(3) > CH(2)Cl(2) > DMF > DMF/H(2)O > CH(3)CN > CH(3)CN/H(2)O. DMF is an exceptional solvent because 3 of the 7 compounds undergo self-catalytic reaction. 9-Nitroanthracene, which has a perpendicular nitro group, is the fastest, while the more compact 1-nitropyrene and 3-nitrofluoranthene, are the slowest degrading compounds.

The variance of bladder and rectal doses calculated from orthogonal and simple stereo films in cervix high-dose-rate brachytherapy.

PURPOSE: To examine the variance in dose to the bladder and rectum during high-dose-rate brachytherapy for cervical cancer for two imaging techniques. An investigation into the patient skin dose from both techniques was also undertaken. METHODS AND MATERIALS: We examined how the variance in dose to critical structures (bladder and rectum) was affected by the degradation of image quality introduced by increasing the lateral separation in a phantom-based study. We also examined the interobserver variation and the reproducibility of C-arm alignment on the variance of the calculated values of the rectal and bladder doses. The relationship between lateral separation and skin entrance dose from collecting images was also investigated. All of these factors were investigated for the standard orthogonal imaging technique and the simple stereo method. RESULTS: It was found that imaging technique and lateral separation had little effect on the variation in the calculated doses to the bladder and rectum. However, it was found that at separations greater than 50 cm, the skin dose from a lateral x-ray increased sharply. CONCLUSIONS: The degradation of image quality for lateral images used to reconstruct cervix applicators does not result in loss of precision in the dose estimates to organs at risk when using the orthogonal technique. However, the skin dose from the lateral image increases markedly with increasing patient separation, making the simple stereo technique a better option for large patients.

Enhanced conversion of DNA radical damage to double strand breaks by 1,2,4-benzotriazine 1,4-dioxides linked to a DNA binder compared to tirapazamine.

Targeting the anticancer compound tirapazamine (3-amino-1,2,4-benzotriazine 1,4-dioxide; TPZ) to DNA by appended binding units has been found to greatly increase the free radical-induced production of both single and double strand breaks under hypoxia compared to TPZ itself. The (*)OH radical, produced upon the radiolysis of aqueous solutions, was used to damage plasmid DNA, and both types of strand breaks were quantified in the absence and presence of TPZ and analogues. Targeted analogues of TPZ show increases of 12-18-fold in single strand breaks, and 60-110-fold in double strand breaks, as compared with TPZ itself. The observed increased formation of double strand breaks under hypoxia is the likely mechanism for the large increase in potency previously demonstrated for a similarly targeted analogue of TPZ as a bioreductive drug (Delahoussaye et al. (2003) Biochem. Pharmacol. 65, 1807-1815). The one-electron reduction potential of the two-electron reduced metabolite of TPZ (the 1-oxide, SR 4317) has been measured as -568 +/- 9 mV, which is sufficiently high to oxidize carbon-centered radicals such as those formed on the sugar moiety of DNA. Targeting the 1-oxide moiety to DNA resulted in a ca. 50% increase in single strand breaks over that seen for TPZ without the dramatic increase in double strand breaks seen for the similarly targeted benzotriazine 1,4-dioxides. These studies support the mechanism by which the reduction of TPZ to an oxidizing radical leads to free radical damage on DNA that can be further oxidized by TPZ or SR4317 (and especially well by DNA-targeted analogues) to yield lesions resulting in strand breakage. The targeting of benzotriazine 1,4-dioxide analogues to DNA by appending binding units to the compounds thus represents an efficient system for inducing strand breaks in DNA.

Dopamine and uric acid act as antioxidants in the repair of DNA radicals: implications in Parkinson's disease.

Dopamine (DA) and uric acid (UA) have been found to undergo a protective reaction effecting the fast chemical repair of oxidative free-radical damage to DNA. This antioxidant reaction does not occur with normal concentrations of other, more abundant, antioxidants and our findings suggest that DA and UA are important for the preservation of the DNA in certain brains cells per se. These studies point to the need for drugs that undergo a similar antioxidant reaction with DNA radicals to prevent or arrest DNA damage associated with Parkinson's disease when the levels of DA and UA fall.

Effect of high-carbon dioxide atmospheres on infestations of apple maggot (Diptera: Tephritidae) in apples.

Short-term storage regimens containing elevated atmospheres of carbon dioxide (CO2) were evaluated for their ability to disinfest newly harvested 'McIntosh' apples of apple maggot, Rhagoletis pomonella (Walsh). Infested fruits containing newly laid eggs were either placed directly into the high-CO2 atmosphere at 10 degrees C to expose this life stage, or else held first for 7 d at room temperature, to allow development to the neonate larval stage. Treatment combinations consisted of three different CO2 levels (10.6, 14.9, and 19.0% CO2) and two periods of exposure (7 and 14 d). Apple maggot eggs subjected to the treatments always exhibited some survival, which was lower for the 14-d than the 7-d exposure periods. In contrast, newly hatched larvae were less able to survive the treatments. The 7-d exposure allowed low levels of survival of this life stage, but virtually none survived the 14-d exposure period. To determine the age at which eggs become more susceptible to high-CO2 atmospheres, infested fruits containing eggs three or 3d old were submitted to a 14-d exposure to 19.0% CO2. Survival of 3-d old eggs was similar to that of eggs exposed at an age of 1 d or less, but this dropped to near zero for 5-d old eggs, indicating an increase in susceptibility sometime during the 3-5-d age range. Fruits exposed to 19.0% CO2 for 14 d were significantly firmer than untreated fruits. No apparent browning, internal breakdown or other fruit defects were detected in any of the treatments.