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Biomedical subjects

D R Holmes

Publications and source records attributed to D R Holmes.

At least 55 records · Page 3Linked to original sources
PubMed2001

Use of a new myocardial centroid for measurement of regional myocardial dysfunction by electron beam computed tomography: comparison with technetium-99m sestamibi infarct size quantification.

RATIONALE AND OBJECTIVES: The study compared the performance of conventional endocardial and epicardial centroid algorithms with the new "myocardial" centroid algorithm in patients with anterior myocardial infarction. "Floating" endocardial or epicardial centroid algorithms, commonly used in tomographic imaging methods to assess regional motion, may misrepresent left ventricular regional myocardial function in the presence of markedly asymmetric left ventricular contraction. METHODS: A new centroid algorithm based on regional myocardial mass distribution was tested in 29 patients with a first anterior myocardial infarction and was compared with conventional centroid algorithms. Direct comparisons in 60 equal sectors at one midventricular level per patient were performed between electron beam computed tomography and technetium-99m sestamibi single-photon emission computed tomography. The thresholds of regional myocardial function used to define infarction were varied for regional ejection fraction from 20% to 40% and for regional wall thickening from 0 to 4 mm. Regression and Bland-Altman analysis were used to compare infarct size by regional myocardial function with infarct size by sestamibi single-photon emission computed tomography. RESULTS: The new myocardial centroid showed the least shift toward infarcted myocardium from diastole to systole and had the highest amplitudes of the measurement curves for regional ejection fraction and regional wall thickening. The optimal regional myocardial function thresholds for each centroid algorithm for regional ejection fraction were endocardial, 30% (R = 0.62; mean difference to sestamibi, -0.5% +/- 22.1% tomographic infarct size points); epicardial, 30% (R = 0.79; mean difference, 2.2% +/- 13.1% tomographic infarct size points); and new myocardial, 25% (R = 0.88; mean difference, -0.6% +/- 9.5% tomographic infarct size points). The optimal thresholds for regional wall thickening were endocardial, 1 mm (R = 0.70; mean difference, -2.2% +/- 14.3% tomographic infarct size points); epicardial, 1 mm (R = 0.78; mean difference, -4.6% +/- 12.7% tomographic infarct size points); and new myocardial, 2 mm (R = 0.71; mean difference, 2.1% +/- 14.1% tomographic infarct size points). The best agreement (R = 0.88) between electron beam computed tomography infarct size and sestamibi single-photon emission computed tomography infarct size was achieved with regional ejection fraction and the new myocardial centroid algorithm. CONCLUSIONS: In asymmetrically contracting left ventricles, the new myocardial centroid algorithm is superior to conventional methods for tomographic analysis of regional myocardial function.

Algorithms↗
PubMed2001

Simvastatin preserves coronary endothelial function in hypercholesterolemia in the absence of lipid lowering.

Recent evidence suggests that some benefit from the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors may occur independent of lipid lowering. We aimed to determine the effect of simvastatin on coronary endothelial function, endothelial NO synthase (eNOS) expression, and oxidative stress in experimental hypercholesterolemia (HC) in the absence of cholesterol lowering. Pigs were randomized to 3 experimental groups: normal diet (N group), high cholesterol diet (HC group), and HC diet with simvastatin (HC+S group) for 12 weeks. Low density lipoprotein cholesterol was similarly increased in the HC and HC+S groups compared with the N group. In vitro analysis of coronary large- and small-vessel endothelium-dependent vasorelaxation was performed. The mean vasorelaxation of epicardial vessels to bradykinin was significantly attenuated in the HC group compared with the N group (32.3+/-1.2% versus 42.9+/-1.6%, respectively; P<0.0001). This attenuation was significantly reversed in the HC+S group (38.7+/-1.5%, P<0.005 versus HC group). The maximal vasorelaxation to substance P was significantly attenuated in the HC group compared with the N group (50.5+/-11.9% versus 79.3+/-5.3%, respectively; P<0.05). This attenuated response was normalized in the HC+S group (74.9+/-4.1%, P<0.05 versus HC group). The maximal arteriolar vasorelaxation to bradykinin was also significantly attenuated in the HC group compared with the N group (71.9+/-4.9% versus 96.8+/-1.34%, respectively; P<0.005). This was reversed in the HC+S group (98.4+/-0.6%, P<0.0001 versus HC group). Western blotting of coronary tissue homogenates for eNOS demonstrated a decrease in protein levels in the HC group compared with the N group, with normalization in the HC+S group. Elevation of plasma F(2)-isoprostanes and thiobarbituric acid-reactive substances, markers of oxidative stress, occurred in the HC compared with the N group. These changes were reversed in the HC+S group. In summary, simvastatin preserves endothelial function in coronary epicardial vessels and arterioles in experimental HC (in the absence of cholesterol lowering) in association with an increase in coronary eNOS levels and a decrease in oxidative stress. These alterations may play a role in the reduction in cardiac events after treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.

Animals↗
PubMed2001

Insulin-like growth factor binding protein-4 protease produced by smooth muscle cells increases in the coronary artery after angioplasty.

Insulin-like growth factor (IGF)-I stimulates vascular smooth muscle cell (VSMC) migration and proliferation, which are fundamental to neointimal hyperplasia in postangioplasty restenosis. IGF-I action is modulated by several high-affinity IGF binding proteins (IGFBPs). IGFBP-4 is the predominant IGFBP produced by VSMCs and is a potent inhibitor of IGF-I action. However, specific IGFBP-4 proteases can cleave IGFBP-4 and liberate active IGF-I. In this study, we document IGFBP-4 protease produced by human and porcine coronary artery VSMCs in culture as pregnancy-associated plasma protein-A (PAPP-A). This was shown by a distinctive IGFBP-4 cleavage pattern, specific inhibition of IGFBP-4 protease activity with PAPP-A polyclonal antibodies, and immunorecognition of PAPP-A by monoclonal antibodies. Furthermore, we found a 2-fold increase in IGFBP-4 protease activity in injured porcine VSMC cultures in vitro (P<0.05). We also evaluated IGFBP-4 protease/PAPP-A expression in vivo after coronary artery balloon injury. Twenty-five immature female pigs underwent coronary overstretch balloon injury, and vessels were examined at defined time points after the procedure. Abundant PAPP-A expression was observed in the cytoplasm of medial and neointimal cells 7, 14, and 28 days after angioplasty (P<0.01 vs control). The highest PAPP-A labeling indices were located in the neointima (36.1+/-2.1%) and the media (31.7+/-1.2%) 28 days after injury. Western blot analysis confirmed increased PAPP-A in injured vessels. PAPP-A, a regulator of IGF-I bioavailability through proteolysis of IGFBP-4, is thus expressed by VSMCs in vitro and in restenotic lesions in vivo. These results suggest a possible role for PAPP-A in neointimal hyperplasia.

Adult↗
PubMed2001

T-cell immunity in acute coronary syndromes.

Acute coronary syndromes (ACS) are complications of atherosclerotic vascular disease that are triggered by the sudden rupture of an atheroma. Atherosclerotic plaque stability is determined by multiple factors, of which immune and inflammatory pathways are critical. Unstable plaque is characterized by an infiltrate of T cells and macrophages, thereby resembling a delayed hypersensitivity reaction. On activation, T cells secrete cytokines that regulate the activity of macrophages, or the T cells may differentiate into effector cells with tissue-damaging potential. Constitutive stimulation of T cells and macrophages in ACS is not limited to the vascular lesion but also involves peripheral immune cells, suggesting fundamental abnormalities in homeostatic mechanisms that control the assembly, turnover, and diversity of the immune system as a whole. This review gives particular attention to the emergence of a specialized T-cell subset, natural killer T cells, in patients with ACS. Natural killer T cells have proinflammatory properties and the capability of directly contributing to vascular injury.

Acute Disease↗
PubMed2001

Calcium embolism of the coronary arteries after percutaneous mitral balloon valvuloplasty.

Two cases of rare, catastrophic calcium emboli to the coronary arteries immediately after percutaneous mitral balloon valvuloplasty are presented. Preoperative echocardiographic findings may identify patients at risk for this complication. These cases should increase the awareness of calcium emboli and lead to consideration of urgent coronary angiography for patients with signs or symptoms of acute coronary occlusion after valvuloplasty.

Aged↗
PubMed2001

Hemorrhagic and vascular complications after percutaneous coronary intervention with adjunctive abciximab.

OBJECTIVES: To examine the frequency and nature of hemorrhagic and peripheral vascular complications associated with use of abciximab during percutaneous coronary intervention and to characterize high-risk patients. PATIENTS AND METHODS: We report the frequency and severity of bleeding and vascular complications recorded prospectively in 2,559 consecutive nonselected patients who underwent percutaneous coronary intervention at Mayo Clinic, Rochester, Minn, between July 1, 1996, and April 30, 1998, 831 of whom received abciximab and 1,728 did not. Abciximab and heparin were administered according to guidelines of the Evaluation of PTCA [percutaneous transluminal coronary angioplasty] to Improve Long-Term Outcome With Abciximab GP IIb/IIIa Blockade (EPILOG). RESULTS: Patients who received abciximab were more likely to be men, were more often treated within 12 hours of an acute myocardial infarction, and were more likely to have received heparin after the procedure (8.7 % vs 4.5%, P<.001). Major bleeding occurred in 18 patients (2.4%) who received abciximab and in 10 patients (0.6%) who did not receive abciximab (P<.001). Minor bleeding occurred in 108 patients (14.3%) and in 92 patients (5.9%), respectively (P<.001). Both major bleeding and minor bleeding were more frequent among patients within 12 hours of an acute myocardial infarction and were more frequent if abciximab had been used. Multivariate analysis revealed that use of abciximab was independently associated with major and minor bleeding. CONCLUSION: In this clinical setting, use of adjunctive abciximab during percutaneous coronary intervention was associated with a significantly increased risk of both major and minor bleeding.

Abciximab↗
PubMed2001

3D localization of implanted radioactive sources in the prostate using trans-urethral ultrasound.

Prostate cancer is the most common cancer diagnosed in men in the United States. Many techniques have been developed to diagnose and treat prostate cancer. 3D Trans-Urethral Ultrasound (TUUS) is a new technique for the diagnosis and treatment of prostate disease. This research focuses on the potential of TUUS for therapy-guidance during and after transperineal interstitial permanent prostate brachytherapy (TIPPB). Computed tomography (CT) is currently used to determine the source locations and the effective radiation dose distribution throughout the tissue after the completion of the procedure. TUUS may be a viable alternative to CT for determining source locations within the prostate. Placement of the TUUS catheter into the urethra provides excellent 2D images of the prostate. In addition, the catheter can be used to acquire 3D volumetric data for 3D analysis of the prostate, associated tissue, and radioactive sources. Initial work on source localization was conducted on an ultrasound-equivalent prostate phantom. Cylindrical dummy radiation sources with diameter of .8 mm and length of 4.5 mm were placed into the prostate phantom for assessment with TUUS. The TUUS imaging device is a 10 fr catheter with a linear array of ultrasonic crystals at one end. The ultrasound catheter operates at 10 MHz and is controlled by the Acuson Sequoia ultrasound workstation. The catheter was placed in the phantom urethra and 3D scans were acquired. A corresponding CT was acquired for comparative purposes. Segmentation of the prostate capsule was done semi-automatically. Dummy radiation seed segmentation was conducted manually. Additional processing was necessary to account for image artifact and correctly reconstruct the seeds. The prostate shell and radioactive source reconstructions provide an excellent 3D representation. Comparison to the CT data suggests that the TUUS data provided: 1) greater resolution and 2) better soft tissue differentiation. The reconstructed sources were measured and corresponded to the physical dimensions of those placed in the phantoms. The method is now being evaluated on cadavers and patients.

Brachytherapy↗
PubMed2001

Anatomy of the first septal perforating artery: a study with implications for ablation therapy for hypertrophic cardiomyopathy.

OBJECTIVE: To determine the variability in the size and distribution of the first septal perforating artery (FSPA). MATERIAL AND METHODS: In this pilot study, 10 fresh autopsy hearts from patients who did not have hypertrophic cardiomyopathy (HCM) or clinical evidence of coronary artery disease were evaluated for the variability in the size of the FSPA. The size of the FSPA was also measured during coronary angiography in 8 patients with HCM who were undergoing alcohol septal ablation. RESULTS: Of the 10 autopsy hearts, 2 had a large FSPA (> or = 1.0 mm in maximal diameter) with prominent septal myocardial distribution, 2 had a medium-sized FSPA (0.5-0.9 mm), 2 had a small FSPA (0.1-0.4 mm), 3 had a tiny FSPA (< 0.1 mm), and 1 had an indiscernible ostium. In 2 patients the FSPA supplied the right ventricular free wall. In 4 patients the basal ventricular septum was incompletely supplied by the FSPA. Of the 8 patients with HCM, the FSPA was larger than 2 mm in diameter in 2 patients, 1 to 2 mm in 4, and smaller than 1 mm in 2. The distance between the left anterior descending coronary artery ostium and the origin of the FSPA ranged between 13.1 and 37.4 mm, indicating a large variation in the size and distribution of the FSPA. CONCLUSIONS: Variability in the size and distribution of the FSPA in patients without HCM was substantial. Areas of the heart other than the basal septum were supplied in some patients by the FSPA. In other patients the FSPA did not supply the entire basal septum. Similar findings were noted in patients with HCM. A detailed evaluation of the distribution of the FSPA may be necessary in all patients with HCM who are undergoing alcohol septal ablation.

Adult↗
PubMed2001

Pathophysiology, diagnosis, and current management strategies for chest pain in patients with normal findings on angiography.

Chest pain syndromes in patients with normal angiographic findings represent a multifactorial pathophysiologic state, which may range from abnormalities in pain perception to abnormalities in endothelial- and non-endothelial-dependent coronary flow reserve associated with myocardial ischemia. Treatment begins with an accurate diagnosis by obtaining a comprehensive history and performing a physical examination, followed possibly by performing functional angiography in those who continue to have symptoms. This approach may help to determine appropriate treatment.

Angina Pectoris↗
PubMed2001

In-stent restenosis.

The decrease in restenosis rates compared with conventional angioplasty, stable angiographic results with a subsequent decreased need for urgent or emergency coronary bypass graft surgery, and reliable treatment of acute or threatened closure resulting from conventional angioplasty have all made stents the treatment of choice for many patients undergoing percutaneous intervention. In-stent restenosis (ISR), however, has become a significant problem. Neointimal hyperplasia with vascular smooth muscle cells is even more exaggerated with stent placement than with conventional angioplasty. In addition, failure to deploy the stent optimally at the time of the initial placement may result in increased restenosis. Symptoms of ISR typically occur within 6 to 9 months following intervention, and range from asymptomatic angiographic narrowing, or even occlusion, to recurrent angina/ischemia or myocardial infarction. Evaluation is by repeat angiography. Treatment with balloon angioplasty is effective for focal in-stent restenotic lesions; for other lesions excimer laser, rotational atherectomy, and directional coronary atherectomy are associated with excellent initial outcome, but long-term outcome of these procedures is unclear. Brachytherapy with both gamma and beta sources has been found to result in improved outcome with less angiographic restenosis and decreased target vessel revascularization. Late thrombosis has been documented in up to 10% of patients treated with vascular gamma brachytherapy, and increased stenosis at the edges of the treated segment is also seen. Prolonged dual antiplatelet therapy and avoidance of a new stent has been shown to reduce late thrombosis in patients treated with vascular brachytherapy.

Angioplasty, Balloon, Coronary↗
PubMed2000

Acute coronary syndromes: extending medical intervention for five days before proceeding to revascularization.

Intensive medical therapy before percutaneous coronary intervention appears to improve results in patients with unstable angina and non-ST-segment elevation myocardial infarction (MI). In this review of treatment strategies for patients with acute coronary syndromes, an "aggressive conservative" approach based on that used in the FRagmin and Fast Revascularisation during InStability in Coronary artery disease (FRISC II) trial is recommended. In FRISC II, an early (but not emergent) invasive therapeutic procedure undertaken within 7 days of starting open-label dalteparin lowered the risk of death and MI in moderate- and high-risk patients and resulted in better and more rapid symptom relief and fewer hospital readmissions than the noninvasive approach. The early treatment period represents a critical juncture in the spectrum of care for patients with unstable angina and affords physicians the best opportunity to educate them about the importance of risk factor modification. Informed consent is also an important issue, particularly in the event of ad hoc coronary intervention. The optimal treatment plan must include considerations of length of hospitalization, medication requirements, and the potential for symptom recurrence or need for hospital readmission. Finally, tailoring therapy for individual patients and establishing appropriate timing of procedures will help ensure the best possible outcome.

Angina, Unstable↗
PubMed2000

Percutaneous coronary intervention in the current era compared with 1985-1986: the National Heart, Lung, and Blood Institute Registries.

BACKGROUND: Although refinements have occurred in coronary angioplasty over the past decade, little is known about whether these changes have affected outcomes. METHODS AND RESULTS: Baseline features and in-hospital and 1-year outcomes of 1559 consecutive patients in the 1997-1998 Dynamic Registry who were having first coronary intervention were compared with 2431 patients in the 1985-1986 National Heart, Lung, and Blood Institute Registry. Compared with patients in the 1985-1986 Registry, Dynamic Registry patients were older (mean age, 62 versus 58 years; P:<0.001) and more often female (32.1% versus 25.5%; P:<0.001). In the Dynamic Registry, procedures were more often performed for acute myocardial infarction (22.9% versus 9.9%; P:<0.001) and treated lesions were more severe (84.5% versus 82.5% diameter reduction; P:<0.001), thrombotic (22.1% versus 11.3%; P:<0.001) or calcified (29.5% versus 10.8%; P:<0.001). Stents were used in 70.5% of Dynamic Registry patients, whereas 1985-1986 patients received balloon angioplasty alone. Procedural success was higher in the Dynamic Registry (92.0% versus 81.8%; P:<0.001) and the rate of in-hospital death, myocardial infarction, and emergency coronary bypass surgery combined was lower (4.9% versus 7.9%; P:=0.001) than in the 1985-1986 Registry. The 1-year rate for CABG was lower in the Dynamic Registry (6.9% versus 12.6%; P:<0.001). CONCLUSIONS: Although Dynamic Registry patients had more unstable and complex coronary disease than those in the 1985-1986 Registry, their rate of procedural success was higher whereas rates of complications and subsequent CABG were lower. Results of percutaneous coronary intervention have improved substantially over the past decade.

Angioplasty, Balloon, Coronary↗
PubMed2000

Effect of abciximab on late adverse events in patients with diabetes mellitus undergoing stent implantation.

Percutaneous coronary intervention (PCI) in patients with diabetes mellitus (DM) is associated with higher rates of adverse cardiac events. Recent data suggest that adverse events are reduced in DM after PCI using stents with abciximab. We performed a retrospective analysis of a prospective PCI registry for all patients with DM who underwent stent placement at the Mayo Clinic from 1995 to 1997 (n = 570), and divided them into 2 groups based on whether abciximab was administered. Characterization and comparison of the clinical and angiographic variables, procedural outcomes, and short- and long-term event rates between groups was performed. The baseline clinical characteristics of the groups were similar, but patients treated with abciximab were more likely to be men with a lower left ventricular ejection fraction. Patients treated with abciximab had more multivessel intervention, saphenous vein graft intervention, and thrombus before intervention. The 30-day mortality rate (0.6% vs 3.0%, p = 0.03) and repeat PCI (0% vs 1.1%, p = 0.03) was lower in patients treated with abciximab. The 30-day rates of bypass surgery, myocardial infarction (MI), and a composite of death, MI, and revascularization were similar. The 1-year event rates did not differ significantly between patients taking and not taking abciximab for the end points of death (8.9% vs 8.8%, p = 0.97), MI (13.3% vs 11.4%, p = 0.57), bypass surgery (10.3% vs 6.2%, p = 0.20), repeat PCI (14.7% vs 15.9%, p = 0.76), and a composite of death, MI, and revascularization (30.4% vs 26.7%, p = 0.43). After adjusting for baseline variables, abciximab did not influence the occurrence of late adverse events.

Abciximab↗
PubMed2000

The PARAGON stent study: a randomized trial of a new martensitic nitinol stent versus the Palmaz-Schatz stent for treatment of complex native coronary arterial lesions.

A new martensitic nitinol stent with improved flexibility and radiopacity was tested to evaluate whether these differences improve initial or long-term outcome. Patients who underwent percutaneous revascularization of a discrete native coronary lesion were randomly assigned to the new stent (PARAGON, n = 349) or to the first-generation Palmaz-Schatz (PS) stent (n = 339). The primary end point was target vessel failure at 6 months (a composite of cardiac or noncardiac death, any infarction in the distribution of the treated vessel, or clinically indicated target vessel revascularization). Secondary end points were, among others, device and procedural success and angiographic restenosis. Mean age was 62 years; diabetes was present in 21% of patients, prior bypass surgery in 6%, and recent infarction in 22% (p = NS for comparison between the 2 randomized arms). The PARAGON stent group had smaller reference vessels (2.97 vs 3.05 mm, p = 0.05), more prior restenosis (8.0% vs 4.5%, p = 0.07), and a longer average stent length (21.3 vs 19.4 mm, p < 0.05). Device success was significantly higher in the PARAGON arm (99.1% vs 94.3%, p < 0.05). Death and infarction at 6-month follow-up were infrequent in both groups. There was no significant difference in death (2.0% vs 1.2%, p = 0.546), but a higher rate of infarction for the PARAGON cohort (9.2% vs 4.7%, p = 0.025). Although target vessel failure (20.3% vs 12.4%, p = 0.005) and target lesion revascularization (12.0% vs 5.9%, p = 0.005) were higher in the PARAGON group, there was no significant difference in 6-month follow-up in in-stent minimal lumen diameter or in the rate of binary angiographic restenosis. Both PARAGON and PS stents are safe and associated with infrequent adverse events. The PARAGON stent can be delivered more frequently than the first-generation PS stent. Although there was no significant difference in in-stent minimal lumen diameter or the frequency of angiographic restenosis, clinical restenosis was more frequent in the PARAGON group.

Adult↗
PubMed2000

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

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

Analysis of Variance↗