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Biomedical subjects

W G Daniel

Publications and source records attributed to W G Daniel.

At least 19 recordsLinked to original sources

Upregulation of CD40-CD40 ligand (CD154) in patients with acute cerebral ischemia.

BACKGROUND AND PURPOSE: Inflammation and hypercoagulability contribute to the development of acute cerebral ischemia. Both can be mediated by the CD40 system. This study investigated whether the CD40 system and related mediators are upregulated in patients with transient ischemic attack (TIA) or stroke. METHODS: Seventeen patients with TIA, 60 patients with complete stroke, and 15 control subjects were investigated. CD154 and P-selectin were analyzed on platelets and CD40 on monocytes during and 3 months after acute cerebral ischemia by double-label flow cytometry. Blood concentrations of soluble CD154 and monocyte chemoattractant protein-1 (MCP-1) were evaluated. RESULTS: Our main findings are as follows: (1) patients with acute cerebral ischemia showed a significant increase of CD154 on platelets and CD40 on monocytes compared with controls; (2) plasma levels of soluble CD154 were significantly higher in these patients; (3) these patients had significantly higher numbers of prothrombotic platelet-monocyte aggregates; (4) the chemoattractant MCP-1 was significantly elevated in cerebral ischemia; and (5) at 3 months' follow-up, upregulation of CD154 still persisted in patients with previous acute cerebral ischemia. CONCLUSIONS: Patients with acute cerebral ischemia show upregulation of the CD40 system, which might contribute to the known proinflammatory, proatherogenic, and prothrombotic milieu found in these patients.

Acute Disease↗

Changes of cerebral blood flow velocities during enhanced external counterpulsation.

OBJECTIVES: Intra-aortic counterpulsation is the most frequently used cardiac assist device. However, there are only few studies of the effects of counterpulsation on cerebral blood flow and these report conflicting outcomes. The new enhanced external counterpulsation (EECP) technique reproduces non-invasively the effects of intra-aortic counterpulsation. In this study, we evaluated effects of EECP on blood pressure (BP) and on cerebral flow velocity (CBFV). SUBJECTS AND METHODS: Twenty-three healthy controls and 15 atherosclerotic patients each underwent a 5-min session of EECP. Before, during and after EECP we monitored heart rate, beat-to-beat radial artery BP and CBFV. RESULTS: EECP induced a second increase in BP and CBFV during diastole with a significant increase of mean BP and a decrease of systolic BP in patients and controls. Mean CBFV increased in both groups during the first 5 s of EECP. After 3 min of EECP, diastolic CBFV was still higher than at baseline, but systolic CBVF was lower than at baseline; mean CBFV was as low as before EECP in the patients and lower than the baseline values in the controls. Three minutes after ending EECP, mean and systolic BP were lower in the patients than the corresponding baseline values. Otherwise, CBFV and BP values did not differ from baseline in patients and controls. CONCLUSION: Cerebral autoregulation ensures the constancy of cerebral blood flow even though EECP creates marked systemic changes. In the patients, the decrease of BP after EECP with maintained CBFV indicates an improved BPCBFV relation and a more economic autoregulation.

Adult↗

Factors associated with coronary artery calcification in young female patients with SLE.

BACKGROUND: With improved survival rates of patients with systemic lupus erythematosus (SLE), damage such as accelerated atherosclerosis gains increasing importance. OBJECTIVE: To identify the prevalence of coronary artery calcifications (CAC) in asymptomatic patients. METHODS: Electron beam tomography (EBT) was performed in 75 female patients with SLE aged <50. The results were correlated with traditional and SLE related factors associated with CAC. 49 women with symptomatic coronary heart disease (CHD) and 279 women without CHD were also analysed. RESULTS: Overall, 21/75 (28%) patients had CAC. Low HDL cholesterol levels <1.40 mmol/l (p=0.03, OR=1.8, 67% v 39%) and cigarette smoking (p=0.01, OR=5.7, 76% v 44%) were identified as factors associated with CAC. Hypertension and high cholesterol were more common in women with CHD (p<0.01) than in those without CHD. SLE related factors were proteinuria (1331 v 465 mg/day, p=0.02), impaired renal function (p=0.02, OR=2.6, 26% v 6%), and high C3 levels (p=0.04, OR=1.8, 65% v 38%). High C3 levels were also more common in symptomatic CHD (p=0.02). The prevalence of Sm antibodies was lower in patients with CAC (15% v 42%, p=0.03). In a multivariate analysis, cigarette smoking, reduced renal function, high C3, and a cumulative steroid dose above 30 g were the most important CAC associated factors in the lupus cohort. CONCLUSION: A subgroup of patients with SLE with CAC without any clinical symptoms of CHD was identified by EBT. Therefore, EBT is useful for assessing asymptomatic atherosclerosis in this group.

Adult↗

Coronary calcifications in young patients with first, unheralded myocardial infarction: a risk factor matched analysis by electron beam tomography.

OBJECTIVE: To compare the presence and extent of coronary calcifications in young patients with first, unheralded acute myocardial infarction with matched controls without a history of coronary artery disease. METHODS: In 102 patients under 60 years of age (19-59 years, mean 41 years; 88% male), electron beam tomography was done 1-14 days after acute myocardial infarction, before any coronary intervention. Coronary calcifications were quantified using the Agatston score. Age related calcium centiles were determined based on the Mayo Clinic "epidemiology of coronary calcification" study, and results were compared with a group of 102 controls without coronary artery disease, matched for sex, age, and risk factors. RESULTS: Calcifications were present in 95.1% of patients with acute myocardial infarction and in 59.1% of controls (p = 0.008). The mean (SD) Agatston score was 529 (901) in the infarct patients versus 119 (213) in the controls (p < 0.001). An Agatston score above the 50th centile was present in 87.2% of infarct patients and 47.0% of controls (p = 0.006), and above the 90th centile in 60.7% of infarct patients and only 5.8% of controls (p = 0.001). CONCLUSIONS: In young patients with their first, unheralded acute myocardial infarction, the presence and extent of coronary calcium are significantly greater than in matched controls.

Adult↗

High-dose intravascular beta-radiation after de novo stent implantation induces coronary artery spasm.

BACKGROUND: Intracoronary brachytherapy is effective in preventing restenosis after coronary interventions. However, in vitro and animal studies have shown that irradiation produces immediate and sustained endothelial dysfunction. This study assesses the clinical relevance of impaired vasomotoric function induced by brachytherapy. METHODS AND RESULTS: We analyzed the occurrence of postradiation coronary artery spasms in 1 animal study and 2 clinical trials investigating the effects of high-dose intracoronary beta-radiation after de novo coronary artery stenting. Irradiated segments (IRSs) proximal and distal to the stent were studied by quantitative coronary angiography after stenting, after radiation, and at the end of the procedure. There was an 67% overall incidence of coronary artery spasm in the IRSs immediately after beta-radiation compared with 9% after sham treatment (P<0.001). Whereas in most cases this phenomenon was only minor or moderate, in 12 cases, 4 (22%) animals and 8 (28%) patients, severe coronary spasm (>90% diameter stenosis) with significant ECG-changes or hemodynamic instability was observed. Relief of spasms was protracted (mean time until complete relief of spasm 423+/-122 seconds) and required repetitive intracoronary administration of nitroglycerin (mean dose: 1.2+/-0.6 mg). CONCLUSIONS: Vasoconstriction is a frequent reaction of coronary arteries after high-dose intracoronary beta-radiation, necessitating repetitive administration of vasodilators.

Animals↗

Initial experience with the Endicor X-sizer thrombectomy device in patients with ST segment elevation myocardial infarction.

We investigated 16 patients with ST segment elevation myocardial infarction who had an occluded coronary artery (TIMI 0) at initial angiogram. Instead of balloon angioplasty and stenting, patients were subjected to thrombectomy (Endicor X-sizer) and stenting. In 15/16 patients the occlusion could be crossed by the thrombectomy device resulting in TIMI flow 3 in all of them. Thereafter, stenting was performed. At final angiogram all 15 patients continued to show TIMI flow grade 3. Twelve-lead ECG was performed prior to and post-intervention. ST elevation was measured as the sum of eight leads for anterior infarction and of five leads for inferior infarction. In 13/15 patients, ECG analysis was possible (2 developed bundle branch block post-intervention). In all 13 patients, a > 50% ST decrease of the initial amount of ST elevation was observed reaching a > 70% reduction in 11 patients. Procedural complications were low (one coronary dissection after thrombectomy) and 30 days follow-up was uneventful. Thrombectomy using the Endicor X-Sizer device may become an attractive mechanical reperfusion strategy for patients with acute myocardial infarction.

Aged↗

[Role of glycoprotein IIb/IIIa inhibitors in the treatment of degenerated aortocoronary saphenous vein grafts].

Treatment of degenerated vein grafts is a large, growing portion of interventional procedures. Because the operative risk of repeat bypass surgery is substantially increased, percutaneous transluminal coronary angioplasty has been accepted as a less invasive treatment in symptomatic patients with significant stenoses of vein grafts. Stent placement has been established in the randomized SAVED trial as a safe and efficient treatment strategy of degenerated saphenous vein grafts, enhancing acute success, reducing the incidence of subsequent angiographic restenosis, and improving event-free survival. Despite coronary stents and new technological innovations like directional and transluminal extraction atherectomy distal embolization is still a frequent occurrence, with a reported incidence of 10-15% associated with an increased in-hospital mortality. Blockade of the platelet surface glycoprotein IIb/IIIa receptors has been convincingly demonstrated to reduce the ischemic complications of angioplasty in native coronary arteries. In degenerated vein grafts the efficacy of glycoprotein IIb/IIIa inhibitors in reducing distal embolization is uncertain. Major clinical events could not be reduced by glycoprotein IIb/IIIa antagonists administered periprocedurally. But prospective randomized trials are lacking. Protection devices could reduce the incidence of distal embolization during interventions in degenerated saphenous vein grafts. The relative role of these devices compared to pharmacologic interventions will require careful assessment in future clinical trials.

Abciximab↗

[Influence of heart rate on image quality and detection of coronary stenoses with multislice spiral CT].

Multi-slice spiral CT (MSCT) permits the detection of coronary stenoses. We investigated the influence of the patient's heart rate (HR) during the scan on stenosis detection and the presence of motion artifacts. In 100 patients MSCT was performed and retrospectively ECG-gated cross-sectional images were reconstructed. 115 of 400 coronary arteries (29%) were unevaluable due to motion artifacts (84/115) or other reasons (31/115). In evaluable arteries, sensitivity was 91% (51/56 high grade stenoses detected), specificity was 89%. With increasing HR, the number of unevaluable arteries increased and overall sensitivity for stenosis detection decreased from 62% (HR < or = 70 bpm) to 33% (HR > 70 bpm). MSCT permits detection of coronary stenoses, but evaluability and accuracy decrease with increasing HR.

Aged↗

[Rescue thrombectomy after stent implantation in a degenerating aortocoronary bypass].

BACKGROUND: Distal showering of atherosclerotic debris or thrombus is a feared event during percutaneous angioplasty of degenerated vein grafts. CASE REPORT: We report on a 66-year-old male patient with a history of coronary artery disease who was admitted into hospital with an acute coronary syndrome. He had had coronary artery bypass graft surgery in 1995. His chest pain resolved under treatment with aspirin, heparin, betablocker, and nitrate. A diagnostic angiogram demonstrated two critical stenoses of the left anterior descending graft. After a continuous infusion of tirofiban administered for 24 h prior to elective angioplasty, a JR 4SH 6 F guiding catheter (Cordis) was positioned. The lesions were crossed with a 0.014" Galeo F wire (Biotronik). A 4 mm x 16 mm stent graft (Jostent, Jomed) was deployed in the distal stenosis and a 4.5 mm x 32 mm self-expandable stent (Magic Wallstent, Boston Scientific) in the proximal stenosis. Thereafter, the patient suffered from chest pain, and the ECG showed ST elevation from V1 to V5. Angiography revealed total occlusion of the left anterior descending artery. An X-Sizer catheter (EndiCOR Medical, Inc.) was introduced and advanced through the vein graft with slow back-and-forth movements. After several aspirations, blood flow was significantly improved. A modest CK elevation (127 U/l) indicated a rather small loss of myocardial tissue. CONCLUSION: Percutaneous revascularization of narrowed aortocoronary saphenous vein grafts is associated with increased risk of distal embolization and "no reflow". The X-Sizer catheter system is compatible with commercially available guiding catheters, and capable of retrieving thrombotic debris after macroembolization from degenerated saphenous vein grafts including the native coronary artery.

Acute Disease↗

Upregulation of CD40 and CD40 ligand (CD154) in patients with moderate hypercholesterolemia.

BACKGROUND: Hypercholesterolemia, a risk factor for cardiovascular disease, is associated with inflammation and hypercoagulability. Both can be mediated by the CD40 system. This study investigated whether the CD40 system is upregulated in patients with moderate hypercholesterolemia and whether it is influenced by therapy with a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. METHODS AND RESULTS: Fifteen patients with moderate hypercholesterolemia and 15 healthy control subjects were investigated. CD154 and P-selectin were analyzed on platelets and CD40 was analyzed on monocytes before and under therapy with the statin cerivastatin by double-label flow cytometry. Blood concentrations of soluble CD154 and monocyte chemoattractant protein-1 (MCP-1) were evaluated. Our main findings were as follows. Patients with moderate hypercholesterolemia showed a significant increase of CD154 and P-selectin on platelets and CD40 on monocytes compared with healthy subjects. Soluble CD154 showed a nonsignificant trend for higher plasma levels in patients. A positive correlation was found for total or LDL cholesterol and CD154, but not for CD40 on monocytes. The latter was upregulated in vitro by C-reactive protein, which was found to be significantly elevated in patients with moderate hypercholesterolemia. CD154 on platelets proved to be biologically active because it enhanced the release of MCP-1, which was markedly elevated in an in vitro platelet-endothelial cell coculture model and in the serum of patients. Short-term therapy with a HMG-CoA reductase inhibitor significantly downregulated CD40 on monocytes and serum levels of MCP-1. CONCLUSION: Patients with moderate hypercholesterolemia show upregulation of the CD40 system, which may contribute to the known proinflammatory, proatherogenic, and prothrombotic milieu found in these patients.

Adult↗

Progression of aortic valve calcification: association with coronary atherosclerosis and cardiovascular risk factors.

BACKGROUND: Recent studies demonstrated an influence of atherosclerotic risk factors on the progression of aortic valve stenosis. The extent of aortic valve calcification (AVC) was also found to be a strong predictor of stenosis progression. We investigated the influence of the LDL cholesterol level (LDL), other standard cardiovascular risk factors, and the extent of coronary calcification (CC) on the progression of AVC quantified by electron beam tomography (EBT). METHODS AND RESULTS: In 104 patients (64.7+/-8 years, 89 male) with an EBT scan positive for AVC, CC and AVC were quantified using a volumetric score. EBT was repeated at a mean interval of 15 months (10 to 36 months), and the progression of AVC and CC was determined. Patients were divided into 2 groups according to LDL: group 1, LDL</=3.36 mmol/L (130 mg/dL), 57 patients; group 2, LDL>3.36 mmol/L (130 mg/dL), 47 patients. Mean values for CC were 546+/-932 mm(3) in scan 1 and 665+/-1085 mm(3) in scan 2 for AVC 324+/-796 mm(3) and 404+/-1076 mm(3), respectively. The mean progression of CC was 27+/-37% (group 1, 16+/-22%; group 2, 39+/-46%, P</=0.001) and of AVC was 25+/-38% (group 1, 9+/-22%; group 2, 43+/-44%, P</=0.001). CONCLUSIONS: Quantification of AVC by EBT permits new insights into the progression of aortic valve sclerosis. We observed a strong influence of LDL cholesterol level on the progression of AVC and CC, suggesting that lipid-lowering therapy may decrease the progression of aortic valve calcification.

Aged↗

Noninvasive coronary angiography by magnetic resonance imaging, electron-beam computed tomography, and multislice computed tomography.

In recent years, several techniques for noninvasive imaging of the coronary artery lumen (noninvasive coronary angiography) have been developed. These techniques include magnetic resonance imaging, electron-beam computed tomography, and, most recently, multislice computed tomography. Each of these techniques has specific advantages and disadvantages. Currently, EBCT seems to permit the most robust coronary artery imaging. In the future, imaging modalities will have to be further improved and validated in order to define specific areas for potential clinical applications.

Clinical Trials as Topic↗

Detection of coronary artery stenoses by contrast-enhanced, retrospectively electrocardiographically-gated, multislice spiral computed tomography.

BACKGROUND: Multislice spiral computed tomography (MSCT) with retrospectively ECG-gated image reconstruction permits coronary artery visualization. We investigated the method's ability to identify high-grade coronary artery stenoses and occlusions. METHODS AND RESULTS: A total of 64 consecutive patients were studied by MSCT (4x1 mm cross-sections, 500-ms rotation, table feed 1.5 mm/rotation, intravenous contrast agent, retrospectively ECG-gated image reconstruction). All coronary arteries and side branches with a luminal diameter >/=2.0 mm were assessed concerning evaluability and the presence of high-grade stenoses (>70% diameter stenosis) or occlusions. Results were compared with quantitative coronary angiography. Of 256 coronary arteries (left main, left anterior descending, left circumflex and right coronary artery, including their respective side branches), 174 could be evaluated (68%). In 19 patients (30%), all arteries were evaluable. Artifacts caused by coronary motion were the most frequent reason for unevaluable arteries. Overall, 32 of 58 high-grade stenoses and occlusions were detected by MSCT (58%). In evaluable arteries, 32 of 35 lesions were detected, and the absence of stenosis was correctly identified in 117 of 139 arteries (sensitivity, 91%; specificity, 84%). If analysis was extended to all stenoses with >50% diameter reduction, sensitivity was 85% (40 of 47) and specificity was 76% (96 of 127). CONCLUSIONS: MSCT with retrospective ECG gating permits the detection of coronary artery stenoses with high accuracy if image quality is sufficient, but its clinical use may presently be limited due to degraded image quality in a substantial number of cases, mainly due to rapid coronary motion.

Aged↗

Monocytes coexpress endothelial and macrophagocytic lineage markers and form cord-like structures in Matrigel under angiogenic conditions.

OBJECTIVES: It has been shown that circulating human non-adherent CD34+ cells coexpressing vascular endothelial growth factor (VEGF)-R2 and AC133 have the capacity to differentiate into adherent mature endothelial cells. However, prior studies have demonstrated that a much bigger subset of primary adherent mononuclear cells can also form endothelial progenitor cells (EPC). To determine the origin of the latter cell population we tested the hypothesis: do monocytes as a firmly adherent and plastic cell type have the potential to differentiate into an endothelial phenotype. METHODS: CD34-/CD14+ monocytes were isolated from human peripheral blood by adherence separation and magnetic bead selection (purity >90%) and cultured on fibronectin-coated plastic dishes (medium containing VEGF 10 ng/ml, basic fibroblast growth factor (bFGF) 2 ng/ml, insulin like growth factor (IGF-1) 1 ng/ml, 20% fetal calf serum). RESULTS: After 2 weeks of culture, using fluorescence activated cell analysis we observed a new expression of the endothelial markers von Willebrand factor (vWf), VE-cadherin (VE) and ec-NOS in 45.2, 12.4 and 9.8% of the cells, respectively. The proportion of cells expressing these markers further increased after 4 weeks (94.2, 89.7 and 58.8% of these cells, respectively). The proportion of CD45 expressing cells remained unchanged during this period. However, after 14 days the specific macrophage antigen CD68 was newly expressed in 62% of the analysed cells with a further increase to 90% after 28 days of culture. In three-dimensional gel (Matrigel the formation of cord- and tubular-like structures was observed. CONCLUSION: The present data indicate that under angiogenic stimulation macrophages develop an endothelial phenotype with expression of specific surface markers and even form cord- and tubular-like structures in vitro suggesting that this cell population may be recruited for vasculogenesis.

Antigens, CD↗