The effects of isoflurane-induced electroencephalographic burst suppression on cerebral blood flow velocity and cerebral oxygen extraction during cardiopulmonary bypass

We investigated the effects of isoflurane-induced burst suppression, monitored with electroencephalography (EEG), on cerebral blood flow velocity (CBFV), cerebral oxygen extraction (COE), and autoregulation in 16 patients undergoing cardiac surgery. The experimental procedure was performed during nonpulsatile cardiopulmonary bypass (CPB) with mild hypothermia (32 degrees C) in fentanyl-anesthestized patients. Middle cerebral artery transcranial Doppler flow velocity, right jugular vein bulb oxygen saturation, and jugular venous pressure (JVP) were continuously measured. Autoregulation was tested during changes in mean arterial blood pressure (MAP) within a range of 40-80 mm Hg, induced by sodium nitroprusside and phenylephrine before (control) and during additional isoflurane administration to an EEG burst-suppression level of 6-9/min. Isoflurane induced a 27% decrease in CBFV (P < 0.05) and a 13% decrease in COE (P < 0.05) compared with control. The slope of the positive relationship between CBFV and cerebral perfusion pressure (CPP = MAP - JVP) was steeper with isoflurane (P < 0.05) compared with control, as was the slope of the negative relationship between CPP and COE (P < 0.05). We conclude that burst-suppression doses of isoflurane decrease CBFV and impair autoregulation of cerebral blood flow during mildly hypothermic CPB. Furthermore, during isoflurane administration, blood flow was in excess relative to oxygen demand, indicating a loss of metabolic autoregulation of flow. IMPLICATIONS: The effects of isoflurane on cerebral blood flow velocity (CBFV) and oxygen extraction (COE) as a function of perfusion pressure were studied. When added to fentanyl anesthesia, isoflurane induced a 27% and 13% decrease in CBFV and COE, respectively. CBFV became more pressure-dependent with isoflurane indicating an impaired autoregulation.     

Single-dose tranexamic acid reduces postoperative bleeding after coronary surgery in patients treated with aspirin until surgery

Tranexamic acid reduces postoperative bleeding after coronary artery bypass grafting. We evaluated the effects of a single dose of tranexamic acid given immediately before cardiopulmonary bypass (CPB) in patients treated with aspirin until the day before surgery. The study was a prospective, randomized, double-blinded, placebo-controlled, parallel-group trial. Eighty patients were included and divided into two groups: one group received tranexamic acid 30 mg/kg, and one group received placebo (0.9% NaCl) as a bolus injection before CPB. Postoperative blood loss was recorded for 16 h. Transfusions of blood products were recorded for the whole hospital stay. Transfusions of packed red cells were given when the hematocrit value was less than 20% during CPB and less than 25% after surgery. The patients in the tranexamic acid group had significantly less postoperative bleeding compared with the patients in the placebo group (mean [SD]) (475 [274] mL versus 713 [243] mL; P < 0.001). An effective inhibition of fibrinolysis was found in patients receiving tranexamic acid. Tranexamic acid reduces postoperative bleeding in coronary artery bypass grafting patients treated with aspirin until the day before surgery. IMPLICATIONS: Continuation of aspirin medication until the day before coronary artery bypass grafting may increase postoperative bleeding. The administration of a single dose of tranexamic acid (30 mg/kg) immediately before cardiopulmonary bypass significantly reduced postoperative bleeding and inhibited fibrinolysis in these patients.     

Heparin-coated circuits and reduced systemic anticoagulation applied to 2500 consecutive first-time coronary artery bypass grafting procedures

BACKGROUND: In contrast to the widespread popularity of off-pump techniques for coronary artery bypass grafting, our institution has chosen a different strategy, emphasizing improvements in the technology for extracorporeal circulation, as well as simplifying surgical and clinical management. The clinical short-term results of this approach were analyzed. METHODS: The on-pump strategy includes routine use of heparin-coated circuits combined with low systemic heparinization (activated coagulation time of more than 250 seconds), intention of total revascularization within limited ischemic times and pump times, minimal use of blood transfusions, early extubation, and rapid postoperative recovery. The data from the first 2,500 consecutive first-time coronary artery bypass grafting patients (January 1998 to February 2002) treated with this protocol were retrospectively analyzed. RESULTS: There were 487 female (median age 68 years) and 2013 male (median age 64 years) patients. A median of four (one to nine) (mean 4.5 +/- 1.2) distal anastomoses were created, and the median aortic cross-clamp time and pump time were 34 and 54 minutes, respectively. At least one internal mammary artery was used in 99.7% of the patients. Blood or bank blood products were given to 118 patients (4.7%). Median extubation time was 1.5 hours. The stroke rate was 0.8%, transient neurologic deficits occurred in 0.6% of the patients, and the incidence of perioperative myocardial infarction was 1.1%. By the fifth day, 91% of the patients were ready for discharge. Seven patients (0.28%) died during their hospital stay. CONCLUSIONS: Coronary artery bypass grafting with heparin-coated cardiopulmonary bypass circuits and reduced systemic anticoagulation resulted in excellent clinical results, with minimal blood transfusions and rapid postoperative mobilization. The high number of grafted coronary arteries indicates complete revascularization in most patients, which is known to be a significant predictor of long-term event-free survival.     

Gadobutrol-enhanced moving-table magnetic resonance angiography in patients with peripheral vascular disease: a prospective,multi-centre blinded comparison with digital subtraction angiography

The purpose of this study was to compare moving-table three-dimensional contrast-enhanced magnetic resonance angiography (CE MRA), using 1.0-mol gadobutrol, with intra-arterial digital subtraction angiography (i.a. DSA) for evaluation of pelvic and peripheral arteries in patients with peripheral arterial occlusive disease. A total of 203 patients were examined in a prospective, multi-centre study at 1.0/1.5 T. Ten vessel segments of one leg were evaluated on-site and by three independent blinded reviewers off-site. One hundred eighty-two patients were evaluable in blinded reading. For pelvis and thigh, there was statistically significant diagnostic agreement between CE MRA and i.a. DSA on-site (94%) and off-site (86-88%). Overall, for detection of clinically significant stenoses, 93% sensitivity and 90% specificity were achieved in on-site evaluation, with 71-76 and 87-93% off-site; for detection of occlusion, sensitivity and specificity on-site were 91 and 97%, with 75-82 and 94-98% off-site. Evaluation was more sensitive on-site than off-site for detection of stenoses and occlusion, whereas specificity was similar. The CE MRA with 1.0-mol gadobutrol gave results comparable to those of i.a. DSA for the larger arteries of pelvis and thigh. Results for calf arteries were compromised by spatial resolution and technical limitations.     

Digital radiography of scoliosis with a scanning method: radiation dose optimization

The aim of this study was optimization of the radiation dose–image quality relationship for a digital scanning method of scoliosis radiography. The examination is performed as a digital multi-image translation scan that is reconstructed to a single image in a workstation. Entrance dose was recorded with thermoluminescent dosimeters placed dorsally on an Alderson phantom. At the same time, kerma area product (KAP) values were recorded. A Monte Carlo calculation of effective dose was also made. Image quality was evaluated with a contrast-detail phantom and Visual Grading. The radiation dose was reduced by lowering the image intensifier entrance dose request, adjusting pulse frequency and scan speed, and by raising tube voltage. The calculated effective dose was reduced from 0.15 to 0.05 mSv with reduction of KAP from 1.07 to 0.25 Gy cm² and entrance dose from 0.90 to 0.21 mGy. The image quality was reduced with the Image Quality Figure going from 52 to 62 and a corresponding reduction in image quality as assessed with Visual Grading. The optimization resulted in a dose reduction to 31% of the original effective dose with an acceptable reduction in image quality considering the intended use of the images for angle measurements. Electronic Publication     

Safety of contrast-enhanced MR angiography employing gadobutrol 1.0 M as contrast material

Our objectives were to evaluate the safety of intravenous 1.0-M gadobutrol injections in patients with an indication for contrast-enhanced magnetic resonance angiography (CE MRA) of supra-aortal, pelvic, or peripheral arteries by examining and assessing adverse events, laboratory values, vital signs and ECG findings for clinical significance. In 435 patients, recruited in three multicenter trials for safety evaluations of the new contrast agent 1.0-M gadobutrol, CE MRA was performed with 1.0- to 1.5-T scanners using three-dimensional gradient-echo sequences and phased-array coils. The study population comprised 312 men and 123 women with a mean age of 60.9 years. Two hundred seven patients had an indication for imaging of body arteries and 228 had an indication for imaging of peripheral arteries. Blood laboratory values and urinalysis results of 124 patients as well as heart rate, blood pressure, and 12-lead-electrocardiogram readings of 93 patients obtained during a follow-up period of up to 72 h after the injection of contrast media were available for safety analysis. Contrast media application was performed as intravenous bolus injection of 1.0-M gadobutrol in fixed doses according to the patients' body weight (b.w.) and indication for CE MRA and was followed by a 20- to 40-ml saline flush. Mean dose actually applied was 0.1 0.27 mmol/kg b.w. Flow rate ranged between 0.2 and 2.0 ml/s. Safety evaluations found a good tolerability with only 4.6% of at least "possibly related" adverse reactions and no clinically relevant changes in blood and urine samples including no transmetallation effect on serum zinc values. Analysis of renal tolerance showed no influence on renal function irrespective of preexisting renal impairment. The ECG analysis (rhythm analysis, pace-setting disturbances, conduction disturbances, and time interval measurements, including uncorrected and corrected QT) showed no clinically relevant effect of the injection of 1.0-M gadobutrol on the cardiac conduction system. Intravenous injection of 1.0-M gadobutrol at a dose of up to 0.1 0.27 mmol/kg b.w. in the indication CE MRA is safe and causes no clinically relevant changes in safety parameters such as heart rate, blood pressure, blood and urine laboratory values, and cardiac conduction system.     

Auto-SENSE perfusion imaging of the whole human heart

PURPOSE: To show the application of auto-sensitivity encoding (SENSE)-a self-calibrating parallel imaging technique-to first pass perfusion imaging of the whole human heart. MATERIALS AND METHODS: The self-calibrating parallel imaging method auto-SENSE was implemented for a saturation recovery turbo-fast low-angle shot (FLASH) sequence on a 1.5-T scanner using a standard four-element body phased array coil. By reducing the acquisition time per slice by a factor of two compared to conventional turbo FLASH imaging, the number of imaged slices could be doubled to six to ten with an unchanged temporal resolution of one image per heartbeat. This technique has been tested in eight healthy volunteers for contrast-enhanced heart perfusion imaging. RESULTS: Auto-SENSE heart perfusion imaging with improved coverage of the human heart could be performed successfully in all volunteers. A first quantitative comparison of perfusion values between the auto-SENSE and the non-SENSE techniques shows good agreement. CONCLUSION: Auto-SENSE allows perfusion imaging of the whole human heart without gaps.     

Comparative analyses of the dynamic properties of the rectum studied by cryo-sections of human cadavers and pelvic CT scans of patients

Optimization of radiotherapy treatment plans based on dose-volume histograms relies on accurate organ delineation. Hollow organs, such as the rectum, are difficult and time-consuming to delineate owing to unclear visualization of the border between wall tissue and filling. Automated hollow organ delineation would be a valuable tool, but its development depends upon improved understanding of the dynamics of the rectum in response to filling. Two reasonable assumptions proposed in the literature are that (1) the rectal wall tissue along a constant length of the rectal cylinder is preserved over time and (2) the rectal wall tissue is distributed homogeneously along the cylinder. Therefore, variations in wall thickness can be explained by variable rectal filling. To investigate these assumptions, transversal cross-sectional areas enclosed by the outer contour (A(out)) and inner contour (A(in)) of the rectum were recorded from digital photographs of cadaver cryo-sections from the U.S. National Library of Medicine's Visible Human Project. In addition, A(out) and A(in) were recorded from 19 CT scans of 5 of our own patients. The transversal cross-sectional area of the wall of the rectum, A(wall)=A(out)-A(in), was calculated. The data derived both from cryo-sections and repetitive CT scans of patients, revealed that there was a significant correlation between A(wall) and A(out), in contradiction to assumption (1) stated above (male cryo-sections: p<0.001, female cryo-sections: p=0.03, repetitive CT scans p<0.001). Moreover, the mean A(wall) calculated from one CT scan differed significantly from the mean A(wall) from other CT scans and was correlated with the mean A(out), i.e. rectal filling (p<0.001). This finding was confirmed by careful analysis of another study (p=0.001) and opposes assumption (2). Hence, the amount of wall tissue within a constant length of rectum is not preserved over time, but increases with increased filling. This implies that the longitudinal length of the rectum decreases in response to distension of the organ.     

Coordinated expression of integrin subunits,matrix metalloproteinases (MMP), angiogenic genes and Ets transcription factors in advanced-stage ovarian carcinoma: a possible activation pathway?

The events that mediate tumor progression in ovarian carcinoma are poorly understood to date. This review summarizes our results studying metastasis-associated molecules in advanced-stage ovarian carcinomas, details the co-expression of mRNA of these genes, and discusses their prognostic role. Fifty-five primary and metastatic FIGO stage III-IV ovarian carcinomas were analyzed for the expression of alpha v and beta1 integrin subunits, the matrix metalloproteinases MMP-2, MMP-9, and MT1-MMP, the MMP inhibitor TIMP-2, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), interleukin-8 (IL-8), PEA3 and Ets-1 using mRNA in situ hybridization. Tumor and adjacent stromal cell expression was scored. The association between integrin subunit expression and the expression of MMP, TIMP-2, angiogenic genes, PEA3 and Ets-1 was statistically analyzed. Alpha v integrin subunit mRNA expression in carcinoma cells showed significant association with that of MMP-2 and IL-8 in this cellular compartment, while the presence of beta1 integrin subunit mRNA showed similar association with that of PEA3, Ets-1, IL-8, bFGF and MMP-2. Expression of beta1 integrin subunit mRNA in stromal cells was associated with that of TIMP-2 and Ets-1 in this compartment. In addition, significant intercellular associations were found between alpha v integrin subunit mRNA expression in carcinoma cells and stromal cell expression of Ets-1, as well as between stromal cell expression of alpha v integrin subunit and labeling for IL-8 in carcinoma cells. The presence of beta1 integrin subunit mRNA in carcinoma cells showed a significant association with that of Ets-1, IL-8 and bFGF in stromal cells, while the presence of beta1 integrin subunit mRNA in stromal cells was associated with tumor PEA3 mRNA expression. To the best of our knowledge, this is the first evidence for coordinated autocrine and paracrine expression of members of these four families of metastasis-associated genes in human cancer. The results of this analysis support experimental data regarding cross-talk between carcinoma cells and peritumoral fibroblasts. They also suggest the existence of a putative activation sequence of metastatic genes, involving the beta1 (and possibly alpha v) integrin subunits, IL-8, PEA3, Ets-1 and MMP in ovarian carcinoma.     

Radiation therapy dose delivery

In an investigation by the Swedish Cancer Society, the present status critical issues and future aspects and potentials in each of nine major areas of radiation therapy research were described by an expert group. The report presented here deals with radiation therapy dose delivery. dose distributions, beam shaping and intensity modulation.