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Biomedical subjects

Werner G Daniel

Publications and source records attributed to Werner G Daniel.

At least 55 records · Page 3Linked to original sources

Assessment of coronary remodeling in stenotic and nonstenotic coronary atherosclerotic lesions by multidetector spiral computed tomography.

OBJECTIVES: This study was designed to investigate whether contrast-enhanced multidetector spiral CT (MDCT) permits assessment of remodeling in coronary atherosclerotic lesions. BACKGROUND: With sufficient image quality, MDCT permits noninvasive visualization of the coronary arteries, but its ability to assess remodeling has not been evaluated. METHODS: Out of 102 patients in whom MDCT (16-slice scanner, intravenous contrast, 0.75-mm collimation, 420 ms rotation) was performed before invasive coronary angiography, 44 patients with high-quality MDCT data sets showing atherosclerotic plaque in a proximal coronary artery segment were chosen for evaluation. In multiplanar reconstructions orthogonal to the coronary artery, the cross-sectional vessel area was measured for the respective lesion and for a reference segment proximal to the lesion. The "Remodeling Index" was calculated by dividing the vessel area in the lesion by the reference segment. Results were correlated to the presence of stenosis (>50% diameter reduction) in invasive angiography. In a subset of 13 patients, MDCT measurements were verified by IVUS. RESULTS: Reference vessel area was not significantly different between nonstenotic versus stenotic lesions (20 +/- 8 mm(2), n = 23 vs. 22 +/- 8 mm(2), n = 21). The mean Remodeling Index was significantly higher in nonstenotic than in stenotic lesions (1.3 +/- 0.2 vs. 1.0 +/- 0.2, p < 0.001). In five stenotic lesions, "negative remodeling" (Remodeling Index < or = 0.95) was observed. Cross-sectional vessel areas and Remodeling Indices measured by MDCT correlated closely to IVUS (r(2) = 0.77 and r(2) = 0.82, respectively). CONCLUSIONS: Multidetector spiral CT may permit assessment of remodeling of coronary atherosclerotic lesions in selected data sets of sufficient quality.

Coronary Angiography↗

Imaging of coronary atherosclerosis using computed tomography: current status and future directions.

Computed tomography (CT) imaging of the coronary arteries, using either electron beam tomography (EBT) or multidetector row CT (MDCT), offers two possibilities to assess coronary atherosclerosis. Without injection of contrast agent, coronary calcifications can be detected and quantified. Their presence and extent correlates to the presence and amount of coronary atherosclerotic plaque. Prospective studies have demonstrated a high predictive value concerning the occurrence of coronary artery disease events and overall mortality. An emerging consensus seems to indicate that calcium imaging may be clinically useful in patients at intermediate risk for coronary artery disease events as determined based on traditional risk factors. In addition, recent studies have shown that after injection of contrast agent and using high-resolution scan protocols, the visualization of noncalcified plaque is also possible with CT techniques. However, data on the accuracy of plaque detection, quantification of plaque volume, and characterization of plaque (eg, lipid-rich vs fibrous) is currently limited, and the prognostic significance of noncalcifed coronary atherosclerotic plaque detection is unclear.

Coronary Artery Disease↗

HMG-CoA reductase inhibitors suppress maturation of human dendritic cells: new implications for atherosclerosis.

The beneficial effects of statins in atherosclerosis have been partly attributed to their immunomodulating functions. Dendritic cells (DC), which are "professional" antigen-presenting cells, were recently detected in atherosclerotic plaques. It is assumed that DC play a critical role in the immunological processes related to atherosclerosis. Thus, we investigated the effects of statins on maturation and antigen-presenting function of DC. Human monocyte-derived DC were incubated with simvastatin or atorvastatin (1-10microM) for different periods (1-48h), and were subsequently stimulated with a cytokine cocktail (1.25ng/ml TNF-alpha, 1ng/ml Il-1beta, and 0.5microg/ml prostaglandin E(2)) to induce maturation. In contrast to untreated DC, statin-preincubated DC exhibited an immature phenotype and a significantly lower expression of the maturation-associated markers CD83, CD40, CD86, HLA-DR, and CCR7. The inhibitory statin effect was completely reversed by mevalonate or geranylgeranyl pyrophosphate. In addition, preincubation with statins significantly reduced the ability of cytokine-stimulated DC to induce T cell proliferation. In the present study, we have shown that statins inhibit the maturation and antigen-presenting function of human myeloid dendritic cells, thus maybe contributing to their beneficial effects in atherosclerosis. Therefore, the use of statins as immunomodulators might also provide a new therapeutic approach to other immunological disorders.

Adjuvants, Immunologic↗

Emergence of dendritic cells in rupture-prone regions of vulnerable carotid plaques.

Dendritic cells (DC), which are critically involved in various immunological disorders, were detected in atherosclerotic plaques in 1995. Since DC might be related to the immunological processes in atherosclerosis (AS), we analyzed the emergence of DC and other inflammatory cells in different stages of AS. Serial cross-sections of 44 carotid specimens were immunohistochemically analyzed for the presence of DC, T cells, macrophages, and HLA-DR. Atherosclerotic specimens were histologically defined as initial lesions, advanced stable, or vulnerable plaques. In initial lesions significantly lower DC numbers were detected than in advanced plaques (P < 0.001). For advanced plaques, DC numbers were significantly higher in vulnerable than in stable plaques (P = 0.005). In contrast to initial lesions, approximately 70% of DC in advanced plaques exhibited a mature phenotype (CD83+, DC-LAMP+), indicating a functional activity of DC. In plaques of patients with acute ischemic symptoms DC numbers were markedly elevated (P = 0.03), whereas significantly lower DC numbers and more often a stable plaque morphology were detected in statin-treated patients (P = 0.02). DC clusters with a strong HLA-DR expression and frequent DC-T cell contacts were located particularly in the rupture-prone plaque regions and at complications. The results of the present study indicate that DC might contribute to plaque destabilization through an activation of T cells.

Aged↗

Comparison of deformation imaging and velocity imaging for detecting regional inducible ischaemia during dobutamine stress echocardiography.

AIMS: To determine whether Doppler based myocardial tissue velocity imaging (TVI) or strain rate imaging (SRI) is more accurate in detecting stress-induced ischaemia during dobutamine stress echocardiography (DSE). METHODS AND RESULTS: Regional myocardial velocity, displacement, strain rate and strain patterns during DSE were investigated in 44 routine patients with known or suspected coronary artery disease. Simultaneous perfusion scintigraphy defined regional ischaemia. Curves and curved-M-mode patterns were analysed and receiver-operating-characteristics of TVI and SRI parameters were compared by their area under the curve (AUC) in the receiver-operating-characteristics. In non-ischaemic segments, peak systolic velocity and strain rate increased significantly. Unlike SRI, TVI parameters had higher values in basal than in apical segments. In 47 segments of 19 segments DSE-induced ischaemia, which was proven by scintigraphy. In ischaemia, velocity and strain rate increased less. Post-systolic shortening (PSS) was always seen in SRI but not regularly in TVI. Peak systolic velocity and systolic displacement were the best TVI-parameters of stress-induced ischaemia (AUC 0.68 and 0.77, respectively.), in SRI it was the ratio of PSS and maximal segmental deformation (AUC=0.95, p < 0.0001). CONCLUSION: Compared to TVI, SRI parameters showed no major apico-basal gradient and had significantly higher diagnostic accuracy, comparable to conventional reading. SRI thus appears superior to TVI for regional ischaemia detection during DSE and may be preferred to support conventional DSE reading.

Blood Flow Velocity↗

Pulsating thoracic tumor caused by extragenital endometriosis in a patient with Noonan syndrome.

We present the case of a 36-year-old woman with Noonan syndrome and congenital heart disease in whom extragenital endometriosis caused an extraordinarily large jelly-like paracardiac and abdominal mass. Protrusion through an intercostal space caused a pulsating subcutaneous tumor on the left lateral thoracic wall. The patient never complained of menstruation-related pain. Histology obtained during several prior surgical interventions had been inconclusive. Thus definitive diagnosis was delayed for years. A literature review revealed no known association between Noonan syndrome and endometriosis.

Abdomen↗

Accelerated reperfusion of poorly perfused retinal areas in central retinal artery occlusion and branch retinal artery occlusion after a short treatment with enhanced external counterpulsation.

BACKGROUND: To date, no satisfactory therapy has become available for patients with acute central retinal artery occlusion (CRAO) or branch retinal artery occlusion (BRAO). Enhanced external counterpulsation (EECP) is a new noninvasive procedure that increases perfusion of inner organs. In the current study, the authors measured the impact of EECP on reperfusion in ischemic retinal tissue. METHODS: In a prospective, randomized study, 20 patients with CRAO or BRAO were included. Ten patients were given hemodilution therapy and 2 hours of EECP, and 10 patients were given regular hemodilution therapy only. Quantification of changes in retinal perfusion was carried out by means of scanning laser Doppler flowmetry (in arbitrary units). RESULTS: Enhanced external counterpulsation caused no observable adverse events. A significant increase in perfusion occurred immediately after EECP in the ischemic retinal areas (57 +/- 19 arbitrary units versus 99 +/- 14 arbitrary units). In contrast, no change was measured in the group not treated with EECP (83 +/- 19 arbitrary units versus 89 +/- 44 arbitrary units). Forty-eight hours later, a significant increase in perfusion could be shown in the ischemic retina of both groups, and no significant difference of perfusion was found between the two groups any longer. CONCLUSION: The current study suggests that EECP could be a clinically useful and safe procedure in patients with CRAO or BRAO to accelerate recovery of perfusion in ischemic retinal areas.

Aged↗

Single-dose nimodipine normalizes impaired retinal circulation in normal tension glaucoma.

PURPOSE: Several studies indicate that calcium channel blockers improve the clinical course of normal tension glaucoma (NTG), whereas the underlying mechanism is not fully investigated. Hemodynamic improvement and neuroprotective effects are discussed. In this study, we measured the hemodynamic effects of nimodipine on retinal circulation. PATIENTS AND METHODS: Sixteen patients with NTG and clinical signs of vasospastic hyperreactivity, such as suffering from extremely cold hands and feet, were consecutively selected out of the local glaucoma registry. Ten healthy age-matched volunteers were included as controls. Retinal capillary blood flow was measured by Scanning Laser Doppler Flowmetry in both eyes before and 90 +/- 10 minutes after a single oral dose of 30 mg nimodipine. RESULTS: Before administration of nimodipine, retinal capillary blood flow was significantly reduced in NTG patients compared with controls (262 +/- 80 vs. 487 +/- 164 AU, P < 0.001). Nimodipine increased retinal capillary blood flow in NTG patients by 91 +/- 73% (P < 0.001) to values of healthy controls (440 +/- 113 vs. 439 +/- 123 AU, P = 0.635). In controls, nimodipine did not show significant effects. CONCLUSIONS: In NTG patients with additional vasospastic symptoms, retinal capillary blood is significantly reduced in comparison with healthy controls. Single-dose nimodipine yields to a normalization of retinal circulation in NTG patients up to values of healthy controls 90 minutes after drug administration.

Blood Circulation↗

Quantification of aortic valve calcification with electron beam tomography: a histomorphometric validation study.

RATIONALE AND OBJECTIVES: The exact quantification of the amount of calcification in aortic valves may be useful for the identification of risk factors for the progression of aortic valve calcification and to evaluate new therapeutic approaches for aortic valve disease. Electron beam tomography (EBT) allows the in vivo detection of calcifications in coronary vessels and in the aortic valve. The aim of this study was to validate the quantification of aortic valve calcification by EBT with in vivo and in vitro investigations. METHODS: In 15 patients (aortic stenosis in 13, aortic regurgitation in 2 cases), EBT was performed before aortic valve replacement (40 cross sections, 3-mm slice thickness, matrix 512 x 512, field of view 28 cm, ECG trigger at 40% of the cardiac cycle). EBT was repeated on the explanted aortic valve using the same protocol. In both data sets, the amount of aortic valve calcification was determined using a volumetric score. In serial cuts of the explanted valve (distance 1 mm), the calcified volume was determined by an independent investigator using histomorphometric analysis. RESULTS: The mean calcified volume of the aortic valves as quantified by EBT was 1650.0 +/- 1401.0 mmł in vivo (EBT1) and 1544.4 +/- 1266.5 mmł in vitro (EBT2). Histomorphometric analysis showed a mean calcified volume of 1555.7 +/- 1272.5 mmł. The mean difference between EBT1 and EBT2 was 4.2 +/- 14.7%, between EBT1 and histomorphometry 3.6 +/- 12.1%, and between EBT2 and histomorphometry -0.5 +/- 5.9%. CONCLUSION: EBT allows accurate in vivo quantification of aortic valve calcifications.

Aged↗

Activated human platelets release connective tissue growth factor.

Connective tissue growth factor (CTGF) is overexpressed in wound healing, fibrosis and advanced atherosclerotic lesions. Platelets adhere to CTGF, suggesting that this protein may be involved in the formation of platelet-rich thrombi at the sites of tissue injury or atherosclerotic plaque rupture. Since platelets contain a wide array of biologically active proteins, we investigated the presence, localization and release of CTGF from these cells. For this purpose, human platelets from healthy donors were washed and stimulated with thrombin or ADP. Following incubation, proteins from unstimulated and stimulated cell lysates and the supernatants were analysed by Western blotting. The experiments showed that unstimulated platelets contain considerable amounts of CTGF, whereas no CTGF was detectable in platelet-poor plasma. To elucidate the origin of CTGF in platelets, we performed immunohistochemical analysis of human bone marrow sections. The analysis showed that although CTGF protein is widely expressed in bone marrow cells, it is not expressed by platelet-producing megakaryocytes, suggesting that CTGF presence in platelets is a result of endocytosis from extracellular environment in bone marrow. Agonist-stimulation of platelets resulted in a significant release of CTGF from the storage granules, with thrombin at 0.1 U/mL being a more potent activator than ADP at 20 micro mol/L. The agonist-dependent CTGF secretion was significantly inhibited by aspirin. In conclusion, CTGF is stored in normal human platelets, and can be released upon platelet activation. Aspirin treatment prevents CTGF release, suggesting that clinical benefits of this drug may involve the inhibition of CTGF secretion.

Adenosine Diphosphate↗

Association of cardiovascular risk factors to aortic valve calcification as quantified by electron beam computed tomography.

OBJECTIVE: To analyze the association among aortic valve calcification, cardiovascular risk factors, and coronary artery calcification using electron beam computed tomography (EBCT). PATIENTS AND METHODS: We analyzed cardiac EBCT data obtained for coronary calcium detection in 1000 consecutively enrolled patients (mean +/- SD age, 57.1 +/- 10 years; 69% men) between January 1, 1998, and July 23, 2001. In all patients, atherosclerotic risk factors (hyperlipidemia, hypertension, diabetes, smoking, and family history of coronary artery disease) were documented. With EBCT, the amount of coronary calcification was determined using the Agatston score, and the amount of aortic valve calcification was measured using a volumetric score. RESULTS: Aortic valve calcification was detected in 177 (17.7%) of the total patient group and was found more frequently in patients with coronary calcification (20.5% in patients with coronary calcium vs 3.8% in patients without coronary calcium; P < .001), hyperlipidemia (19.5% vs 6.5%; P < .001), hypertension (21.7% vs 13.9%; P = .01), or diabetes (30.7% vs 16.6%; P = .002). The volume of aortic valve calcification was significantly higher in patients with vs without hyperlipidemia (P < .001), hypertension (P = .002), and diabetes (P = .001). In a multivariable logistic regression analysis, adjusted for age and sex, hyperlipidemia (P = .001) and the presence of coronary calcification (P < .001) were significant predictors of aortic valve calcification. CONCLUSION: A significant association exists among atherosclerotic risk factors, coronary calcification, and the presence and amount of aortic valve calcification.

Aged↗

Detection of calcified and noncalcified coronary atherosclerotic plaque by contrast-enhanced, submillimeter multidetector spiral computed tomography: a segment-based comparison with intravascular ultrasound.

BACKGROUND: We investigated the ability of multidetector spiral computed tomography (MDCT) to detect atherosclerotic plaque in nonstenotic coronary arteries. METHODS AND RESULTS: In 22 patients without significant coronary stenoses, contrast-enhanced MDCT (0.75-mm collimation, 420-ms rotation) and intravascular ultrasound (IVUS) of one coronary artery were performed. A total of 83 coronary segments were imaged by IVUS (left main, 19; left anterior descending, 51; left circumflex, 4; right coronary, 9). MDCT data sets were evaluated for the presence and volume of plaque in the coronary artery segments. Results were compared with IVUS in a blinded fashion. For the detection of segments with any plaque, MDCT had a sensitivity of 82% (41 of 50) and specificity of 88% (29 of 33). For calcified plaque, sensitivity was 94% (33 of 36) and specificity 94% (45 of 47). Coronary segments containing noncalcified plaque were detected with a sensitivity of 78% (35 of 45) and specificity of 87% (33 of 38), but presence of exclusively noncalcified plaque was detected with only 53% sensitivity (8 of 15). If analysis was limited to the 41 proximal segments (segments 1, 5, 6, and 11 according to American Heart Association classification), sensitivity and specificity were 92% and 88% for any plaque, 95% and 91% for calcified plaque, and 91% and 89% for noncalcified plaque. MDCT substantially underestimated plaque volume per segment as compared with IVUS (24+/-35 mm3 versus 43+/-60 mm3, P<0.001). CONCLUSIONS: The results indicate the potential of MDCT to detect coronary atherosclerotic plaque in patients without significant coronary stenoses. However, further improvements in image quality will be necessary to achieve reliable assessment, especially of noncalcified plaque throughout the coronary tree.

Calcinosis↗

Relation between coronary calcium and 10-year risk scores in primary prevention patients.

In 380 patients, coronary calcifications were quantified by electron beam tomography and compared with the predicted 10-year cardiovascular event risk determined by the Framingham equation, Adult Treatment Panel III tables, and the PROCAM algorithm. The correlation between the amount of calcium and the predicted cardiac event risk was low (correlation coefficient range 0.19 to 0.28). The assessment of coronary calcium may thus potentially yield information that is additive to the analysis of traditional risk factors.

Age Factors↗

PMN/platelets coinfused in guinea pig hearts Exposed to low-flow ischemia have no additive cardiodepressive effect.

Recent studies revealed an additive cardiodepressive effect of polymorphonuclear granulocytes (PMN) and thrombocytes in hearts exposed to a no-flow ischemia. To find out whether or not this is also true for isolated guinea pig hearts exposed to a low-flow ischemia, the current study was performed. PMN or thrombocytes, together or separately, were applied as a 1-min bolus (1,000/microl or 20,000/microl, respectively) during ischemia or in reperfusion in the presence of thrombin (0.3 U/ml perfusate). Recovery of external heart work and intracoronary cell retention were quantified in percent. Sole application of PMN or platelets during ischemia and reperfusion significantly compromised myocardial function, whereas coapplication of PMN and platelets did not exhibit any further cardiodepressive effect. Coapplication of cells almost prevented intracoronary platelet retention during ischemia and in reperfusion, as opposed to sole platelet application. Known blockers of endogenously released anti-platelet substances like nitric oxide, PGI(2) or adenosine did not mediate a further aggravation of myocardial dysfunction. The platelet-activating factor (PAF) antagonist WEB 2170 BS, however, significantly improved recovery of external heart work during ischemia and in reperfusion. This indicates that an additive cardiodepressive effect of PMN and platelets in working guinea pig hearts exposed to a low-flow ischemia, cannot be demonstrated, whereas PAF antagonists seem to be cardioprotective, under these conditions. Even addition of fibrinogen to the perfusate, did not show an additive cardiodepressive effect of coapplication of PMN and platelets.

Animals↗

Strain-rate imaging during dobutamine stress echocardiography provides objective evidence of inducible ischemia.

BACKGROUND: Interpretation of dobutamine stress echocardiography (DSE) is subjective and strongly dependent on the skills of the reader. Strain-rate imaging (SRI) by tissue Doppler may objectively analyze regional myocardial function. This study investigated SRI markers of stress-induced ischemia and analyzed their applicability in a clinical setting. METHODS AND RESULTS: DSE was performed in 44 patients with known or suspected coronary artery disease. Simultaneous perfusion scintigraphy served as a "gold standard" to define regional ischemia. All patients underwent coronary angiography. Segmental strain and strain rate were analyzed at all stress levels by measuring amplitude and timing of deformation and visual curved M-mode analysis. Results were compared with conventional stress echo reading. In nonischemic segments, peak systolic strain rate increased significantly with dobutamine stress (-1.6+/-0.6 s-1 versus -3.4+/-1.4 s-1, P<0.01), whereas strain during ejection time changed only minimally (-17+/-6% versus -16+/-9%, P<0.05). During DSE, 47 myocardial segments in 19 patients developed scintigraphy-proven ischemia. Strain-rate increase (-1.6+/-0.8 s-1 versus -2.0+/-1.1 s-1, P<0.05) and strain (-16+/-7% versus -10+/-8%, P<0.05) were significantly reduced (both P<0.01 compared with nonischemic). Postsystolic shortening (PSS) was found in all ischemic segments. The ratio of PSS to maximal segmental deformation was the best quantitative parameter to identify stress-induced ischemia. Compared with conventional readings, SRI curved M-mode assessment improved sensitivity/specificity from 81%/82% to 86%/90%. CONCLUSIONS: During DSE, SRI quantitatively and qualitatively differentiates ischemic and nonischemic regional myocardial response to dobutamine stress. The ratio of PSS to maximal strain may be used as an objective marker of ischemia during DSE.

Coronary Angiography↗

Detection of coronary artery stenoses with thin-slice multi-detector row spiral computed tomography and multiplanar reconstruction.

BACKGROUND: We analyzed the accuracy of multi-detector row spiral computed tomography (MDCT) using a 16-slice CT scanner with improved spatial and temporal resolution, as well as routine premedication with beta-blockers for detection of coronary stenoses. METHODS AND RESULTS: Seventy-seven patients with suspected coronary disease were studied by MDCT (12x0.75-mm cross-sections, 420 ms rotation, 100 mL contrast agent IV at 5 mL/s). Patients with a heart rate above 60/min received 50 mg atenolol before the scan. In axial MDCT images and multiplanar reconstructions, all coronary arteries and side branches with a diameter of 1.5 mm or more were assessed for the presence of stenoses exceeding 50% diameter reduction. In comparison to invasive coronary angiography, MDCT correctly classified 35 of 41 patients (85%) as having at least 1 coronary stenosis and correctly detected 57 of 78 coronary lesions (73%). After excluding 38 of 308 coronary arteries (left main, left anterior descending, left circumflex, and right coronary artery in 77 patients) classified as unevaluable by MDCT (12%), 57 of 62 lesions were detected, and absence of stenosis was correctly identified in 194 of 208 arteries (sensitivity: 92%; specificity: 93%; accuracy: 93%; positive and negative predictive values: 79% and 97%). CONCLUSIONS: MDCT coronary angiography with improved spatial resolution and premedication with oral beta-blockade permits detection of coronary artery stenoses with high accuracy and a low rate of unevaluable arteries.

Adrenergic beta-Antagonists↗

Percutaneous occlusion of femoral artery pseudoaneurysm by para-aneurysmal saline injection.

The increasing number of coronary interventions and more aggressive anticoagulation is associated with a larger number of iatrogenic femoral pseudoaneurysms (PAs). The majority of PAs clot spontaneously or can be repaired by ultrasound-guided compression or ultrasound-guided thrombin injection. The therapeutic armamentarium for the remaining PAs ranges from different interventional procedures to surgical occlusion. In a small case series, we describe our initial experiences with a new, less invasive approach after unsuccessful compression therapy. Ultrasound-guided injection of 52 +/- 33 ml saline beneath the communication tract of the PA yields to rapid occlusion in six consecutive patients. During 4 weeks of follow-up, the PAs remained occluded in all patients and surgical intervention could be avoided.

Aged↗