Oncogenic Ras/Src cooperativity in pancreatic neoplasia.

Pancreas cancer is one of the most lethal malignancies and is characterized by activating mutations of Kras, present in 95% of patients. More than 60% of pancreatic cancers also display increased c-Src activity, which is associated with poor prognosis. Although loss of tumor suppressor function (for example, p16, p53, Smad4) combined with oncogenic Kras signaling has been shown to accelerate pancreatic duct carcinogenesis, it is unclear whether elevated Src activity contributes to Kras-dependent tumorigenesis or is simply a biomarker of disease progression. Here, we demonstrate that in the context of oncogenic Kras, activation of c-Src through deletion of C-terminal Src kinase (CSK) results in the development of invasive pancreatic ductal adenocarcinoma (PDA) by 5-8 weeks. In contrast, deletion of CSK alone fails to induce neoplasia, while oncogenic Kras expression yields PDA at low frequency after a latency of 12 months. Analysis of cell lines derived from Ras/Src-induced PDA's indicates that oncogenic Ras/Src cooperativity may lead to genomic instability, yet Ras/Src-driven tumor cells remain dependent on Src signaling and as such, Src inhibition suppresses growth of Ras/Src-driven tumors. These findings demonstrate that oncogenic Ras/Src cooperate to accelerate PDA onset and support further studies of Src-directed therapies in pancreatic cancer.

Evaluation of coronary atheroma by 64-slice multidetector computed tomography: Comparison with intravascular ultrasound and angiography.

BACKGROUND: Recent improvements in multidetector computed tomography (MDCT) with 64-slice scanners have allowed acquisition of a coronary study in 5 s to 6 s, with good temporal and spatial resolution. Previous studies have reported an underestimation of plaque burden by MDCT. Whether shorter scan times can allow correct assessment of plaque volume requires comparison with intravascular ultrasound (IVUS). METHODS: Patients (n=30) scheduled for coronary angiography also underwent MDCT and IVUS examinations within 96 h. MDCT examination was performed with a 64-slice scanner. Nitroglycerin was administered before all imaging procedures. MDCT, quantitative coronary angiography (QCA) and IVUS analyses were performed by observers blinded to other results. Plaque volumes were determined by MDCT and IVUS in one vessel, and maximum percentage diameter stenosis was identified in each coronary segment by MDCT and QCA. RESULTS: The mean (+ or - SD) plaque volume was determined to be 179.1 + or - 78.9 mm(3) by MDCT and 176.1 + or - 87.9 mm(3) by IVUS. There was a strong positive correlation for plaque volume between MDCT and IVUS (r=0.84, P<0.0001). Percentage diameter stenosis assessed by MDCT and QCA also correlated well (r=0.88 per patient and r=0.87 per vessel, P<0.0001 for both). The maximum percentage diameter stenosis per vessel was 38.1 + or - 30.2% with MDCT and 34.1 + or - 27.6% with QCA. The sensitivity and specificity of MDCT in detecting stenoses above 50% per vessel were 100% and 91.0%, respectively. CONCLUSIONS: Plaque volumes measured by 64-slice MDCT and IVUS correlate well, without systematic underestimation. The sensitivity and specificity of MDCT to detect stenoses greater than 50% by QCA are excellent with the administration of nitroglycerin before imaging.

Role of Gab2 in mammary tumorigenesis and metastasis.

Overexpression of the adaptor/scaffolding protein Gab2 has been detected in primary human breast cancer cells and cell lines, although its functional significance in breast carcinogenesis is not fully understood. Here, we show a requirement for Gab2 in promoting mammary tumor metastasis. Although Gab2 expression levels were elevated in mammary tumors induced by the Neu (ErbB-2) oncogene, homozygous deletion of Gab2 in mice had only a modest effect on the initiation of Neu-induced mammary tumors. Notably, ablation of Gab2 severely suppressed lung metastasis. Gab2-deficient cancer cells displayed normal Akt activities, and their proliferative rate in vitro was similar to control cells. However, Gab2(-/-) cancer cells exhibited decreased migration and impaired Erk activation, and the defects were rescued by re-introduction of Gab2 into Gab2(-/-) cells. These findings suggest that although Gab2 overexpression may confer growth advantage to tumor cells, the functional requirement for Gab2 in mammary tumor initiation/growth may be dispensable, and that Gab2 may have a prominent role in promoting mammary tumor metastasis.

Early quantitative coronary angiography of saphenous vein grafts for coronary artery bypass grafting harvested by means of open versus endoscopic saphenectomy: a prospective randomized trial.

OBJECTIVE: Endoscopic saphenectomy is associated with a decreased incidence of wound complications without an increase in histologic trauma or endothelial dysfunction in published reports. Concern remains about the patency of saphenous vein grafts harvested endoscopically and the development of early intimal hyperplasia. The purpose of this study was to compare early quantitative coronary analysis of saphenous vein grafts used for coronary artery bypass grafting harvested with the open versus endoscopic techniques. METHODS: Forty patients undergoing primary coronary artery bypass grafting surgery with at least 1 saphenous vein graft were randomized preoperatively to open versus endoscopic saphenectomy with bipolar cauterization of side branches. Quantitative coronary angiography was performed a mean of 3 months (range, 1-9 months) after the operation. RESULTS: There was no statistically significant difference in the patency rates of internal thoracic artery grafts between the open and endoscopic groups and no statistically significant difference in the patency rates of saphenous vein grafts between both groups (85.2% vs 84.4%, P =.991). Quantitative coronary angiography showed no difference in graft stenosis (>or=50% of the internal diameter of the graft) in the body of the saphenous vein grafts in the open versus endoscopic saphenectomy groups (3.7% vs 0%, P =.280). CONCLUSION: Angiographic appearance and patency rates of saphenous vein grafts harvested with the endoscopic technique are similar to those of saphenous vein grafts harvested with the open technique. These results support the use of endoscopic saphenectomy because of the known lower incidence of wound and infectious complications and superior functional results.

Stent placement to prevent restenosis after angioplasty in small coronary arteries.

BACKGROUND: Lesions in small-diameter vessels (<3 mm) define a group with distinct clinical and morphological characteristics. There is an inverse relationship between vessel size and angiographic restenosis rate. This study assessed whether stents reduce angiographic restenosis in small coronary arteries compared with standard balloon angioplasty. METHODS AND RESULTS: We randomly assigned 351 symptomatic patients needing dilatation of 1 native coronary vessel between 2.3 and 2.9 mm in size to angioplasty alone (n=182) or stent implantation (n=169). The primary end point was angiographic restenosis at 6 months. Secondary end points included death, myocardial infarction, bypass surgery, and target vessel revascularization in hospital and at 6 months. There were no significant differences between groups in terms of major in-hospital complications. There was a trend toward fewer in-hospital events in the stent group (3% versus 7.1% in angioplasty group, P=0.076). Crossovers to stent occurred in 37 patients (20.3%). Repeat angiography at 6-month follow-up was performed in 85.3% of patients. Angiographic restenosis occurred in 28% of the stent group and 32.9% of the angioplasty group (P=0.36). Target vessel revascularization was required in 17.8% versus 20.3% of patients (P=0.54), respectively. CONCLUSIONS: Stenting and standard coronary angioplasty are associated with equal restenosis rate in small coronary arteries. With a lower in-hospital complication rate, stenting may be a superior strategy in small vessels.

Late (> 48 hr) myocardial infarction after PTCA: clinical and angiographic characteristics of infarction related or not to the angioplasty site.

Since late myocardial infarctions after percutaneous coronary interventions have not been well characterized, we intended to evaluate the characteristics of myocardial infarctions occurring > 48 hr after balloon angioplasty of native coronary arteries or saphenous vein grafts. The Montreal Heart Institute database (1985-1996) was interrogated for all patients readmitted with a diagnosis of MI more than 48 hr after successful percutaneous transluminal coronary angioplasty (PTCA). We compared the clinical, procedural, and angiographic variables between MIs related or not to the index PTCA site. One hundred and ninety-three patients presented with late myocardial infarction (MI) following balloon angioplasty. The median time elapsed between PTCA and MI was 55 days compared to 968 days when MI was unrelated to the PTCA site. MIs related to the PTCA site were more likely non-Q-wave (76% vs. 35%, P = 0.0001) with less marked CK-MB rise. Angiography showed less complex lesions (63% vs. 90%, P = 0.001) and better thrombolysis in myocardial infarction (TIMI) grade flow (TIMI II to III, 66% vs. 56%, P = 0.01) when the culprit lesion was at the PTCA site. Independent predictors of MI at the PTCA site were vein graft dilation, female sex, and residual stenosis post-PTCA. Myocardial infarctions occurring late after PTCA have a distinct time course and present specific characteristics according to their relationship or not to the previously dilated site.

Randomized trial comparing intravenous nitroglycerin and heparin for treatment of unstable angina secondary to restenosis after coronary artery angioplasty.

BACKGROUND: The treatment of unstable angina targets the specific pathophysiological thrombotic process at the site of the active culprit lesion. In unstable angina due to a restenotic lesion, smooth muscle cell proliferation and increased vasoreactivity may play a more important role than thrombus formation. Therefore, the relative benefits of nitroglycerin and heparin might differ in unstable angina associated with restenosis compared with classic unstable angina. METHODS AND RESULTS: We randomized 200 patients hospitalized for unstable angina within 6 months after angioplasty (excluding those with intracoronary stents) to double-blind administration of intravenous nitroglycerin, heparin, their combination, or placebo for 63+/-30 hours. Recurrent angina occurred in 75% of patients in the placebo and heparin-alone groups, compared with 42.6% of patients in the nitroglycerin-alone group and 41.7% of patients in the nitroglycerin-plus-heparin group (P<0.003). Refractory angina requiring angiography occurred in 22.9%, 29.2%, 4. 3%, and 4.2% of patients, respectively (P<0.002). The odds ratios for being event free were 0.24 (95% CI, -0.13 to 0.45, P=0.0001) for nitroglycerin versus no nitroglycerin and 0.98 (95% CI, -0.55 to 1. 73, P=NS) for heparin versus no heparin. No patient died or suffered myocardial infarction. CONCLUSIONS: Intravenous nitroglycerin is highly effective in preventing adverse ischemic events (recurrent or refractory angina) in patients with unstable angina secondary to restenosis, whereas heparin has no effect.

Reliability of mechanical and phased-array designs for serial intravascular ultrasound examinations--animal and clinical studies in stented and non-stented coronary arteries.

BACKGROUND: Both mechanical and multi-element intravascular ultrasound designs have potential advantages and limitations that may impact on their value for clinical and research purposes. Determination of the reproducibility of measurements is critical before a given system can be used in studies such as regression of atherosclerosis trials. METHODS: We performed serial intravascular ultrasound imaging with catheters using mechanical and phased-array designs in stented and non-stented coronary arteries in dogs and in patients. RESULTS: Both systems correlated well for areas (r > or = 0.90, p < 0.0001) and diameters (r > or = 0.84. p < 0.0001) in dogs and in patients. There was a slight difference between multi-element and mechanical designs for measurements of area (mean difference in dogs and in patients: -0.24 and 0.96 mm2, p < 0.055) and diameter (-0.08 and 0.16 mm, p < 0.0001). The reproducibility of the multi-element system for reanalysis of the same frames and for analysis of serial pullbacks was similar to the same measurements with the mechanical system (r > or = 0.96 for all measurements). The differences in absolute and relative variability between the mechanical and phased-array designs, both for reanalysis of same frames and serial pullbacks, were very small. CONCLUSIONS: Although multi-element and mechanical intravascular ultrasound designs are not strictly interchangeable, their similar reproducibility and the small differences in measurements demonstrate that both designs are acceptable alternatives for trials of regression of atherosclerosis. Determination of the variability for serial pullbacks of both designs was also important to assess the statistical power of such trials.

Value of exercise electrocardiography in the detection of restenosis after coronary angioplasty in patients with one-vessel disease.

Exercise treadmill testing (ETT) is considered an unreliable method for detection of restenosis after percutaneous transluminal coronary angioplasty (PTCA). The studies on which this belief is based have used quantitative coronary angiography (QCA) as a reference. The inherent limitations of angiography have been demonstrated by intravascular ultrasound (IVUS). To determine the value of ETT for detecting restenosis when IVUS criteria are used to define restenosis, we studied 29 patients with angiographically documented 1-vessel coronary disease (<35% stenosis in all nondilated segments) who underwent angioplasty. ETT was performed < or =2 weeks before follow-up angiography and IVUS imaging. Only patients without any abnormalities precluding an accurate reading of the ST segment during ETT were included. Restenosis was defined as a > or =50% diameter stenosis by QCA criteria and as a cross-sectional area narrowing of > or =75% by IVUS. The ETT was positive in 12 patients and restenosis was documented by QCA and IVUS in 38% and 48% of cases, respectively. Sensitivity, specificity, and positive and negative predictive values of ETT when QCA was used as a reference were 55%, 67%, 50%, and 71%, respectively. This corresponded to an accuracy of 62% when compared with QCA. Sensitivity, specificity, and positive and negative predictive values were 79%, 93%, 92%, and 82% when ETT was compared with IVUS, with an accuracy of 86% (p = 0.002). Thus, ETT is a reliable noninvasive method for detecting the presence of restenosis after PTCA in patients with 1-vessel coronary artery disease. The presence of > or =75% cross-sectional narrowing shown by IVUS is well correlated with > or =1-mm ST-segment depression at follow-up ETT after PTCA.

Geometric features of coronary artery lesions favoring acute occlusion and myocardial infarction: a quantitative angiographic study.

OBJECTIVES: We sought to identify the angiographic predictors of a future infarction, to study their interaction with time to infarction, patient risk factors and medications, and to evaluate their clinical utility for risk stratification. BACKGROUND: Identification of coronary lesions at risk of acute occlusion remains challenging. Stenosis severity is poorly predictive but other stenosis descriptors might be better predictors. METHODS: Eighty-four patients with an acute myocardial infarction and a coronary angiogram performed within the preceding 36 months (baseline angiogram), and after infarction were selected. All coronary stenoses (from 10% to 95% lumen diameter reduction) at baseline angiogram were analyzed by computer-assisted quantification. Each of the 84 lesions responsible for the infarction (culprit) was compared with the nonculprit stenoses (controls) in the same patient. RESULTS: Culprit lesions were more symmetrical (symmetry index +15%; p < 0.001), had steeper outflow angles (maximal angle +4 degrees; p < 0.001), were more severe (percent stenosis +5%; p = 0.001) and longer (+ 1.5 mm, p = 0.01) than controls. The symmetry index and the outflow angles were the two independent predictors of infarction at three-year follow-up. Stenosis severity predicted only infarctions occurring within 1 year after angiography. In moderately severe stenoses (40% to 70% stenosis), stratification using the symmetry index and outflow angles accurately predicted lesions remaining free of occlusion and infarction at three-year follow-up. CONCLUSIONS: Better characterization of stenosis geometry might help to understand the pathophysiologic mechanisms triggering coronary occlusion and to stratify patients for improved care.

Quantitative angiographic assessment of coronary anastomoses performed without cardiopulmonary bypass.

BACKGROUND: The quality of the anastomosis performed during coronary artery bypass grafting without cardiopulmonary bypass is a current concern, and myocardial wall restraining devices have been designed to optimize results. A quantitative angiographic analysis was performed to assess coronary anastomoses performed on beating hearts. METHODS: We studied 34 patients who underwent coronary artery bypass grafting without cardiopulmonary bypass between February 1996 and April 1997. The left internal thoracic artery was anastomosed to the left anterior descending coronary artery in all patients. Coronary angiograms were performed 4 +/- 2 days after the operation. The diameter of the anastomoses was quantified by computer-assisted analysis of grafts and native coronary arteries at the toe and heel of the anastomosis. RESULTS: Five of the patients who underwent coronary artery bypass without a stabilizer (n = 20) had stenoses of the internal thoracic artery grafted to the left anterior descending coronary artery of more than 50% at the level of the anastomosis proper, 3 had stenoses at the heel of the coronary anastomosis, and 5 had stenoses at the toe. One of the patients in whom a stabilizer was used (n = 14) had a stenosis of more than 50% at the anastomosis, and 1 had stenosis at the heel. Eight patients in whom the anastomoses were performed without stabilization (8/20, 40%) had stenoses of more than 50%, whereas there was only 1 stenosis of more than 50% of coronary luminal diameter among the patients in whom the operation was performed with a stabilizer (P =.02). CONCLUSION: The quantitative angiographic evaluation suggests that left internal thoracic artery graft to left anterior descending coronary artery anastomoses have a lesser degree of intraluminal stenosis when performed with the use of a myocardial wall stabilizer.

Effects of probucol on vascular remodeling after coronary angioplasty. Multivitamins and Protocol Study Group.

BACKGROUND: We have shown that probucol reduces restenosis after balloon angioplasty. Whether probucol acted via prevention of neointimal formation or improvement in vascular remodeling could not be addressed by angiography and required the use of intravascular ultrasound (IVUS). METHODS AND RESULTS: Beginning 30 days before angioplasty, 317 patients were randomly assigned to receive probucol, multivitamins, combined treatment, or placebo. Patients were then treated for 6 months after angioplasty. IVUS examination was performed immediately after angioplasty and at follow-up in 94 patients (111 segments). The cross section selected for serial analysis was the one at the angioplasty site with the smallest lumen area at follow-up. In the placebo group, lumen area decreased by -1. 21+/-1.88 mm2 at follow-up, and wall area and external elastic membrane (EEM) area increased by 1.50+/-2.50 and 0.29+/-2.93 mm2, respectively. Change in lumen area, however, correlated more strongly with the change in EEM area (r=0.53, P=0.002) than with the change in wall area (r=-0.13, P=0.49). Lumen loss was -1.21+/-1.88 mm2 for placebo, -0.83+/-1.22 mm2 for vitamins, -0.25+/-1.17 mm2 for combined treatment, and -0.15+/-1.70 mm2 for probucol alone (P=0.002 for probucol, P=0.84 for vitamins). Change in wall area was similar for all groups. EEM area increased by 0.29+/-2.93 mm2 for placebo, 0. 09+/-2.33 mm2 for vitamins only, 1.17+/-1.61 mm2 for combined treatment, and 1.74+/-1.80 mm2 for probucol only (P=0.005 for probucol). CONCLUSIONS: Lumen loss after balloon angioplasty is due to inadequate vessel remodeling in response to neointimal formation. Probucol exerts its antirestenotic effects by improving vascular remodeling after angioplasty.

Comparison of ionic and nonionic low osmolar contrast media in relation to thrombotic complications of angioplasty in patients with unstable angina.

BACKGROUND: Acute complications of percutaneous transluminal coronary angioplasty (PTCA) are more common in patients with unstable coronary syndromes. The objective of this study was to prospectively determine the differences between ionic and nonionic low osmolar contrast media (LOCM) on potential risk of acute complications, particularly abrupt vessel closure, in patients with unstable angina undergoing PTCA. METHODS: A total of 210 patients with 278 lesions were randomized to receive either ionic or nonionic LOCM during PTCA. Quantitative coronary angiographic measurements and assessment of filling defects were made by experienced observers who were blinded to the type of contrast media used. RESULTS: The baseline clinical and angiographic characteristics, the immediate postangioplasty results, and clinical outcome were similar in both groups. Subacute recoil, defined as the difference between minimal luminal diameter (in millimeters) at 0 and 15 minutes after angioplasty, was significantly greater in patients receiving nonionic LOCM (0.17 +/- 0.36 mm vs 0.07 +/- 0.18 mm, p = 0.004). A filling defect abnormality attributable to dissection, thrombus, or a combination of the two was noted in similar proportions of the two groups. Although nonsignificant, more thrombus was noted in the nonionic group (21 of 129 vs 15 of 141, p = NS). The abrupt vessel closure rate was similar in the two groups and was only 1.9% in the first 24 hours. However, 17 (8.3%) patients had a repeat PTCA at 15 minutes (9 ionic vs 8 nonionic). CONCLUSION: In patients with unstable angina the choice of ionic or nonionic LOCM does not appear to significantly affect the clinical outcome of PTCA.

Prevention of restenosis after angioplasty in small coronary arteries with probucol.

BACKGROUND: Restenosis remains the major limitation of coronary angioplasty. Coronary stents have reduced the incidence of restenosis in selected patients with relatively large vessels. No strategies to date have demonstrated a beneficial effect in vessels < 3.0 mm in diameter. We have shown in the MultiVitamins and Probucol (MVP) Trial that probucol, a potent antioxidant, reduces restenosis after balloon angioplasty. The purpose of this study was to determine whether the benefit of probucol therapy is maintained in the subgroup of patients with smaller coronary vessels. METHODS AND RESULTS: We studied a subgroup of 189 patients included in the MVP trial who underwent successful balloon angioplasty of at least one coronary segment with a reference diameter < 3.0 mm. One month before angioplasty, patients were randomly assigned to one of four treatments: placebo, probucol (500 mg), multivitamins (beta-carotene 30000 IU, vitamin C 500 mg, and vitamin E 700 IU), or probucol plus multivitamins twice daily. The treatment was maintained until follow-up angiography was performed at 6 months. The mean reference diameter of this study population was 2.49+/-0.34 mm. Lumen loss was 0.12+/-0.34 mm for probucol, 0.25+/-0.43 mm for the combined treatment, 0.35+/-0.56 mm for vitamins, and 0.38+/-0.51 mm for placebo (P=.005 for probucol). Restenosis rates per segment were 20.0% for probucol, 28.6% for the combined treatment, 45.1% for vitamins, and 37.3% for placebo (P=.006 for probucol). CONCLUSIONS: Probucol reduces lumen loss and restenosis rate after balloon angioplasty in small coronary arteries.

Probucol and multivitamins in the prevention of restenosis after coronary angioplasty. Multivitamins and Probucol Study Group.

BACKGROUND: Oxidizing metabolites generated at the site of coronary angioplasty can induce chain reactions that may lead to restenosis. Antioxidants may counter oxidative stress and modify neointimal formation and vascular remodeling. Experimental data and small clinical studies have suggested that antioxidants may prevent restenosis after angioplasty. In a double-blind, randomized trial, we studied whether drugs with antioxidant properties decrease the incidence and severity of restenosis after angioplasty. METHODS: One month before angioplasty, 317 patients were randomly assigned to receive one of four treatments: placebo, probucol (500 mg), multivitamins (30,000 IU of beta carotene, 500 mg of vitamin C, and 700 IU of vitamin E), or both probucol and multivitamins-all given twice daily. Patients were treated for four weeks before and six months after angioplasty. Patients received an extra 1000 mg of probucol, 2000 IU of vitamin E, both probucol and vitamin E, or placebo 12 hours before angioplasty, according to their treatment assignments. Base-line and follow-up angiograms were interpreted by blinded investigators using a quantitative approach. RESULTS: The mean (+/-SD) reduction in luminal diameter six months after angioplasty was 0.12 +/- 0.41 mm in the probucol group, 0.22 +/- 0.46 mm in the combined-treatment group, 0.33 +/- 0.51 in the multivitamin group, and 0.38 +/- 0.50 mm in the placebo group (P = 0.006 for those receiving vs. those not receiving probucol, and P = 0.70 for those receiving vs. those not receiving vitamins. Restenosis rates per segment were 20.7 percent in the probucol group, 28.9 percent in the combined-treatment group, 40.3 percent in the multivitamin group, and 38.9 percent in the placebo group (P = 0.003 for probucol vs. no probucol). The rates of repeat angioplasty were 11.2 percent. 16.2 percent, 24.4 percent, and 26.6 percent, respectively (P = 0.009 for probucol vs. no probucol). CONCLUSIONS: The antioxidant probucol is effective in reducing the rate of restenosis after balloon coronary angioplasty.

[Coronary artery bypass grafting without cardiopulmonary bypass: angiographic evaluation of a preliminary experience]. / La chirurgie de pontages coronariens faits sans circulation extracorporelle: evaluation angiographique de l'expérience préliminaire.

BACKGROUND: Coronary artery bypass grafting (CABG) without cardiopulmonary bypass has been proposed to decrease morbid events related to the circuit and the blood pump. OBJECTIVE: To evaluate quantitatively coronary anastomoses with CABG without cardiopulmonary bypass. SETTING: Between February and December 1996, 19 patients underwent CABG, through a median sternotomy in 12 patients and an anterior minithoracotomy in seven patients. Twenty internal thoracic artery grafts and seven saphenous vein grafts were studied by quantitative angiography in the immediate postoperative period (4 +/- 2 days). Diameters of native coronary arteries and grafts were analyzed by computer. PATIENTS: Patients averaged 57 +/- 8 years of age, with triple vessel coronary disease in three patients, double vessel disease in nine patients and single vessel disease in seven patients. Twelve patients underwent a single thoracic artery graft to the left anterior descending artery and seven patients underwent a double graft to the anterior descending and the right coronary artery. RESULTS: Hospital stay averaged 5 +/- 2 days, operating time averaged 144 +/- 30 mins and ischemic occlusion of the left anterior descending coronary artery averaged 20 +/- 8 mins. Serum creatine kinase MB fraction averaged 11 +/- 7 U/L and 25 +/- 37 U/L, 1 and 24 h, respectively, after surgery. Diameter stenosis of the native coronary artery averaged 19 +/- 26% proximal to the anastomosis, 36 +/- 31% distal to the anastomosis and 27 +/- 32% at the anastomotic site of internal thoracic artery grafts. One native coronary artery distal to the anastomosis was occluded and an occluded anastomosis was reopened by percutaneous angioplasty 72 h after surgery. Saphenous vein grafted to the right coronary artery had only minimal stenosis at anastomotic sites. CONCLUSION: This initial experience with CABG without cardiopulmonary bypass suggests that adequate coronary anastomosis can be performed in selected patients.

Permanent Electronic Storage of Angiographic Images in the Catheterization Laboratory: High-Resolution and Real-Time Acquisition on Optical Laserdiscs.

The use of electronic ÒfilmlessÓ media for long-term archiving of coronary angiograms has been impeded by the problems of image storage and data transfer among institutions. Although long-term analogue storage of the images is presently feasible, and much less costly than digital storage, processing has been limited to a 625 lines video format, not optimal for high quality images. We developed a bi-directional 1249/625 lines converter, able to store and to replay high resolution (1249 lines) video images, from Component Record Video (CRV) Optical Laser (Analogue) Videodisks. Image quality and medical relevance were evaluated five ways: 1) Outside experts compared 593 static images stored on CRV discs to the same images stored in a high-resolution digital format blinded to source of image. The four experts found no visual or medical difference in 98% of evaluated images and minor differences in the remainder. The differences in the remaining images were not consistent among experts. 2) Two of the experts also compared the enhanced CRV optically stored image to the image obtained on simultaneously recorded 35mm cine film, and found the enhanced CRV stored image to be superior or similar, but never inferior to the film image. 3) 90 representatives from 63 outside institutions compared images from both a digital hard drive and the enhanced CRV optical (analogue) storage displayed at a Windows based digital workstation. During the test they were blinded as to the source of the images. The representatives found no difference in image resolution, quality, diagnostic accuracy, and medical relevance. 4) We evaluated quantitative coronary angiography (QCA) on standard coronary test phantoms using enhanced CRV stored images digitally processed. The correlation of the enhanced CRV image to the actual size of the phantom vessels was similar to the results obtained in the literature from digitally stored images. 5) 78 arterial measurements ranging 0.65 to 4.85 mm were evaluated both from the digital hard disc (D) and the CRV optical disc (CRV), using the same QCA analytical package. The correlation coefficient and the Standard Error of the Estimate between D and CRV values were respectively 0.997 and 0.076, no systematic over or underestimation occurred, and the mean variability was inferior to 0.1 mm. CONCLUSION: High-Resolution CRV-optical storage represents a cost-effective solution for excellent image quality equivalent to digitally stored images, permitting permanent electronic archiving inside the cath-lab, and allowing digital image processing and digital image communication.

'True' fasting serum insulin level, insulin resistance syndrome and coronary artery disease.

BACKGROUND: Increased fasting serum insulin level not associated with hypoglycemia is considered to be a practical indicator of the insulin resistance syndrome, a frequent risk factor for atherosclerosis in industrialized countries. However, in most studies, insulin was measured by using antibodies which cross-react with proinsulin and 31/32, 32/33 split products of insulin. We re-examined the correlations between the insulin resistance syndrome and 'true' fasting serum insulin level. METHODS: We studied 242 post-menopausal women (age 63 +/- 8 years), a population in whom insulin resistance syndrome is particularly frequent. Serum insulin was measured by a recent specific microparticle immunoassay. RESULTS: There was a significant correlation between elevated 'true' fasting serum insulin level and various constituents of the insulin resistance syndrome, such as obesity, dyslipidemia (hypertriglyceridemia, increased apolipoprotein B and decreased high-density lipoprotein cholesterol and apolipoprotein A1 concentrations), increased serum glucose, uric acid levels, and plasminogen activator inhibitor type I concentration, as well as increased frequency of diabetes. There was also a correlation between insulin level and various manifestations of coronary artery disease: patients in the highest quartile of 'true' insulin level had significantly more entirely occluded coronary arteries than in the lowest one. Similarly, in the highest insulin quartile more patients had occluded arteries with lumen diameter stenoses greater than 50% (P < 0.05) and more of them had history of previous myocardial infarction approaching the level of significance (P = 0.0587) than in the lowest one. Most of these correlations were also noted in nondiabetic people. CONCLUSIONS: An increase of 'true' fasting serum insulin level is a useful practical index to identify patients with the insulin resistance syndrome exposed to increased risk of coronary artery disease.

Validation of coronary artery saphenous vein bypass graft diameter measurements using quantitative angiography.

The accepted value for reproducibility (true change) is two standard deviations (SD) of the differences between repeat measurements. It has been well established for coronary artery measurements using several different quantitative coronary angiography (QCA) systems, but it has not been well documented for saphenous vein grafts (SVG). The purpose of this study was to assess, using the Cardiovascular Measurement System (CMS), the measurement reproducibility of 24 vein grafts from 24 patients who had symptom-directed control angiography. Three equal graft segments were studied separately. Focal narrowings expressed in percent stenosis varied from 5 to 80% (mean 20.8 +/- 15.9%). The average minimum lumen diameter (MLD) was 3.07 +/- 0.81 mm and the average interpolated reference diameter (Ref. D) was 3.87 +/- 0.58 mm. We assessed the reproducibility of measurements obtained from two separate imagings of the graft in the same view but at least 20 minutes apart, near the beginning and at the end of the angiographic procedure (simulating baseline and end-trial examinations). The SD for differences in measurements (variability) was 0.183 mm for the MLD, 0.193 mm for the Ref.D, 0.184 mm for the mean diameter (Mean D) and 3.72% for the percent diameter stenosis (PDS). A reasonable true change cut-off for SVG measurements in our laboratory is > or = 0.4 mm for the minimum and mean lumen diameters, and > or = 10% for the PDS, when QCA is obtained with the QCA-CMS analytical software package.