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Biomedical subjects

W G Daniel

Publications and source records attributed to W G Daniel.

At least 73 records · Page 4Linked to original sources

Decreased plasma concentrations of L-hydroxy-arginine as a marker of reduced NO formation in patients with combined cardiovascular risk factors.

Patients with metabolic syndrome represent a group with extensive cardiovascular risk factors for the development of atherosclerosis, which may be preceded by an impairment of endothelial function. Endothelial dysfunction is characterized by a reduced availability of bioactive nitric oxide, the principal mediator of endothelium-dependent vasodilation. In the present study we assessed NO synthesis in vivo by measuring the NO-related amino acids L-arginine and L-citrulline and in particular the stable intermediate compound N(omega)-hydroxy-L-arginine (L-NHA) in patients with metabolic syndrome by using high-performance liquid chromatography (HPLC) analysis. As a prerequisite to our study, we measured the amino acid concentrations in 31 healthy volunteers to investigate gender and age differences. To prove whether blood drawn from peripheral veins reflects plasma concentrations of the whole vessel system, several blood samples from different regions were obtained from patients undergoing elective left and right heart catheterization. In the latter group, no significant differences were noted among the plasma concentrations between the different sample sites. In healthy volunteers, there were no significant differences in plasma concentrations of any one specific amino acid between males and females or age groups. The main finding of the study is that the intermediate product of NO synthesis, L-NHA, is significantly reduced in the plasma samples of patients with a metabolic syndrome as compared with samples from healthy control subjects. The plasma concentrations of the NO precursor L-arginine and the end product of NO synthesis, L-citrulline, were unchanged. In conclusion, our results suggest that plasma levels of L-NHA are independent of age and gender and are not different at various locations within the vascular system. In a group of patients at high risk for the development of atherosclerosis, we found reduced plasma concentrations of L-NHA, either caused by a decreased endothelial NO synthase activity or caused by an increased breakdown of L-NHA by pathways independent of NO synthase, resulting in a reduced availability of L-NHA for NO synthesis.

Adult↗

Prenatal diagnosis of QT prolongation by magnetocardiography.

Magnetocardiography constitutes a new tool for monitoring fetal cardiac activity. The fetal magnetocardiogram (FMCG) recorded noninvasively over the maternal abdomen is detectable with high temporal resolution and permits analysis of all parts of the PQRST waveform. In this way measurements of cardiac time intervals, including the QT interval, become possible. The following article constitutes the first report of antenatal detection of QT prolongation in two fetuses by FMCG.

Adult↗

Contrast enhanced electron beam computed tomography to analyse the coronary arteries in patients after acute myocardial infarction.

OBJECTIVE: To evaluate the accuracy of contrast enhanced electron beam computed tomography (EBCT) after acute myocardial infarction in determining patency of the infarct related artery and detecting high grade stenoses and occlusions in the coronary vessels. DESIGN: Case study using blinded comparison with invasive coronary angiography. PATIENTS: 36 patients (mean age 53 years) 4-70 days after acute myocardial infarction. INTERVENTIONS: The patients were studied by EBCT and invasive coronary angiography. For EBCT, 50 axial images of the heart (3 mm slice thickness) were acquired. They were triggered by the ECG during breath holding, after intravenous injection of contrast agent. The original images, surface reconstructions, and maximum intensity projections were evaluated for the presence of high grade stenoses and occlusions of the coronary arteries. MAIN OUTCOME MEASURES: EBCT results were compared with invasive coronary angiography. RESULTS: Of a total of 144 coronary arteries (left main, left anterior descending, left circumflex, and right coronary artery in 36 patients), 29 (20%) were unevaluable by EBCT. In the remaining arteries, 33 of 36 high grade lesions were correctly detected (92% sensitivity). Specificity was also 92% (73/79). Patency of the infarct related artery was correctly detected in 15 of 16 cases (94%). Five of the 14 occluded infarct related arteries (35%) were mistaken as stenotic but patent, and six could not be assessed. CONCLUSIONS: EBCT is very accurate in detecting significant coronary artery lesions in patients after acute myocardial infarction, but differentiation between occluded and patent infarct related arteries is currently unreliable.

Adult↗

In-plane coronary arterial motion velocity: measurement with electron-beam CT.

PURPOSE: To determine the speed of and changes in the speed of coronary arterial movement during the cardiac cycle with electron-beam computed tomography (CT). MATERIALS AND METHODS: With electron-beam CT, 20 consecutive cross-sectional images were acquired at the mid right coronary artery (with 50-msec acquisition time, 8-msec intersection delay, 7-mm section thickness, and intravenous administration of 40 mL of contrast agent) in 25 patients. On the basis of the displacement of the left anterior descending, left circumflex, and right coronary arterial cross sections from image to image, movement velocity in the transverse imaging plane was calculated and was correlated with the simultaneously recorded electrocardiogram. RESULTS: The velocity of in-plane coronary arterial motion varied considerably during the cardiac cycle. Peaks were caused by ventricular systole and diastole and by atrial contraction. The mean velocity was 46.6 mm/sec +/- 12. 5 (SD). The mean velocity of right coronary arterial movement (69.5 mm/sec +/- 22.5) was significantly faster than that of the left anterior descending (22.4 mm/sec +/- 4.1) or the left circumflex coronary artery (48.4 mm/sec +/- 15.0). The lowest mean velocity (27. 9 mm/sec) was at 48% of the cardiac cycle. CONCLUSION: The lowest velocity of coronary arterial movement, which displays considerable temporal variation, was at 48% of the cardiac cycle.

Aged↗

Pneumatic external counterpulsation: a new noninvasive method to improve organ perfusion.

Pneumatic external counterpulsation, which is operated by applying electrocardiographic-triggered diastolic pressure via air-filled cuffs to the vascular limbs of lower limbs, is a relatively new therapeutic option for patients with angina pectoris and cerebrovascular diseases like transient ischemic attacks or sudden deafness. In this study, an augmentation in flow volume in the carotid, renal, and hepatic arteries from 20% to 25% and in the coronary arteries from 20% to 40%, as well as an increase in stroke volume by 12% was demonstrated; this shows the therapeutic results in patients with diseases caused by disturbed organ perfusion.

Adult↗

Role of Ca2+-ATPase inhibitors in activation of cytosolic phospholipase A2 in human polymorphonuclear neutrophils.

In the present study, we investigated the involvement of Ca2+-signaling and protein kinases in the effect of Ca2+-ATPase inhibitors on the activation of cytosolic phospholipase A2 (cPLA2) in human polymorphonuclear neutrophils. We found that activity and mobility on electrophoresis gels of the cPLA2 protein were significantly increased by f-Met-Leu-Phe (fMLP), 12-myristate 13-acetate (PMA) and the Ca2+-ATPase inhibitors, thapsigargin and cyclopiazonic acid. This effect was completely suppressed by staurosporine. Calphostin C partially inhibited the fMLP- and PMA-induced cPLA 2 activation, but had no influence on thapsigargin- and cyclopiazonic acid-treated cells. Thapsigargin and cyclopiazonic acid also showed no effect on protein kinase C activity. However, the thapsigargin- and cyclopiazonic acid-induced cPLA2 activation was completely inhibited by the tyrosine kinase inhibitor, erbstatin, and Ca2+ chelator, EGTA. In addition, the cPLA2 activity was reduced after pretreatment with the mitogen-activated protein kinase kinase inhibitor PD98059. The arachidonic acid release was significantly reduced in cells pretreated with the cPLA2 inhibitor, AACOCF3. Furthermore, we found that the human neutrophil cPLA2 cDNA contain a Ca2+-dependent-lipid binding domain which shares homology to several other enzymes such as protein kinase C and phospholipase C. Our results suggest that tyrosine kinases and the MAP kinase cascade are involved in Ca2+-ATPase inhibitor-induced activation and phosphorylation of cPLA2. Protein kinase C is not required in this event.

Arachidonic Acid↗

Popliteal entrapment syndrome: non-invasive diagnosis and complete recovery after surgery in an 11-year-old boy.

We present an unusual case of popliteal entrapment syndrome type I in an 11-year-old boy. Presenting symptoms were exercise-related pain and pallor in his left lower leg. The diagnosis of popliteal entrapment syndrome was established by acral plethysmography, colour-coded Doppler sonography and MRI. After myotomy of the gastrocnemius muscle the symptoms resolved completely. Post-operative duplex scan showed normal blood flow, even in plantar flexion of the foot.

Arterial Occlusive Diseases↗

[Transesophageal imaging of a coronary fistula in simultaneous endocarditis lenta].

A 61 year old diabetic patient with bacterial endocarditis probably caused by a congenital coronary fistula is presented. The fistula was already detected by transthoracic echocardiography. Transesophageal color-Doppler echocardiography identified the precise localization and course of the fistula. Additionally, in some parts of the fistula echogenic material could be seen that decreased in size after antibiotic treatment. Therefore, it was considered as corresponding to bacterial vegetations. Coronary angiography disclosed an ectopic aneurysmatic and elongated circumflex coronary artery. Thus, even in rare conditions such as coronary fistulas transesophageal echocardiography may be helpful to allow detection of morphological substrate of associated infective endocarditis.

Coronary Thrombosis↗

Angiotensin II-induced superoxide anion generation in human vascular endothelial cells: role of membrane-bound NADH-/NADPH-oxidases.

BACKGROUND: Angiotensin II (ANG II) mediated hypertension accelerates atherosclerosis (AS) and thereby increases the incidence of myocardial infarction (MI). On the other hand, superoxide anion (O2-) is involved in the modification of low density lipoproteins, inhibition of prostacyclin (PGI2) formation and breakdown of nitric oxide. These events finally lead to rapid progression of AS and MI. In the present study, we investigate whether ANG II can induce O2- release from human vascular endothelial cells (HVECs) and the possible mechanisms involved. METHODS AND RESULTS: The expression of ANG receptors subtype-1 (AT-1) and subtype-2 (AT-2) were identified by using reverse transcription polymerase chain reaction and sequence analysis. The O2- production was dose-dependently increased in HVECs treated with ANG II (10(-7)-10(-9) M) and with a maximum rate after 1 h of incubation. This event was significantly inhibited by pretreatment of cells with the specific AT-1 blocker losartan (10(-7) M) and to a lesser extent by the specific AT-2 receptor blocker PD123319 (10(-7) M). The combined incubation of both receptor blockers was even more effective. In addition, our lucigenin-enhanced chemiluminescence assay showed that the activity of plasma membrane-bound NADH-/NADPH-oxidases derived from ANG II-treated cells was also significantly increased, this effect was reduced in cells pretreated with losartan or to lesser extent by PD123319. However, the activity of xanthine oxidase remained unchanged in response to ANG II. Furthermore, the basal O2- release from HVECs was inhibited in cells treated with angiotensin-converting enzyme (ACE) inhibitor, Lisinopril (10(-6) M), and this event could be reversed by ANG II. CONCLUSION: ANG II induces O2- release in HVECs via activation of membrane-bound NADH-/NADPH-oxidase, an effect, that is mediated by both AT-1 and AT-2 receptors. This suggests that acceleration of AS and MI in ANG II-mediated hypertension may at least be due to ANG II-induced O2- generation from vascular endothelial cells. In this case, the ACE inhibitors and the ANG receptor antagonists may act as causative "antioxidants".

Angiotensin II↗

Priming of superoxide anion in polymorphonuclear neutrophils by brain natriuretic peptide.

In acute coronary syndromes such as unstable angina and myocardial infarction, serum concentration of brain natriuretic peptide, a cardiac hormone with potent vasodilatatory, natriuretic and diuretic activities, is elevated. Little is known about the effect of elevated BNP plasma concentration on free radical-mediated tissue damage in these states. We investigated the influence of human BNP 32 and its fragment BNP 7-32 on the production of superoxide anion by PMN, a major cause for myocardial damage. Although BNP showed itself no stimulatory potential on superoxide anion release in PMN, it enhanced significantly the stimulatory potential of cell stimuli such as fMLP or phorbol 12-myristate 13-acetate (PMA) in PMN. Thus our data show that the cardiac-derived hormone BNP influences an important function of PMN. This 'priming' effect of BNP on PMN may contribute to the tissue damage occuring during acute coronary syndromes.

Animals↗

Beta-blockers reduce the release and synthesis of endothelin-1 in human endothelial cells.

BACKGROUND: Endothelins play an important role in cardiovascular diseases, and clinical trials have shown a reduction in endothelin levels after long-term treatment of chronic heart failure with beta-adrenergic antagonists. It is not known, however, whether this effect is caused by haemodynamic changes associated with the use of beta-adrenergic antagonists or by direct interaction of beta-blockers with human endothelial cells. The aim of this study was to determine whether beta-adrenergic antagonists have an influence on endothelin-1 (ET-1) synthesis and release in human endothelial cells. METHODS: Pretreatment of cultured endothelial cells from human umbilical veins (HUVECs) with different concentrations of the non-selective beta-blocker propranolol, the beta 1-blocker metoprolol and the beta 1-blocker and beta 2-agonist celiprolol (all 10(-7)-10(-4) mol L-1) was found to reduce ET-1 production. This ET-1-reducing effect was even more pronounced in thrombin-stimulated cells (10(-5) mol L-1 of propranolol, metoprolol and celiprolol: 19% +/- 5.8%, 25% +/- 4% and 37% +/- 5.2% respectively). RESULTS: Quantitative reverse transcriptase polymerase chain reaction and Northern blotting confirmed an inhibitory effect of the beta-blocker on biosynthesis. Furthermore, the ET-1-reducing effect of propranolol, metoprolol and celiprolol was not due to a compensatory increase in prostacyclin and was not reversible by N-nitro-L-arginine. CONCLUSION: The effect of beta-adrenergic antagonists on ET-1 production of the endothelium may at least partially explain the efficacy of beta-blockers in the treatment of diseases such as advanced heart failure, essential hypertension as well as acute coronary syndromes.

6-Ketoprostaglandin F1 alpha↗

Coronary arteries: MR angiography with fast contrast-enhanced three-dimensional breath-hold imaging--initial experience.

Gadolinium-enhanced, three-dimensional, breath-hold magnetic resonance (MR) coronary angiography was performed in two healthy volunteers and 11 patients suspected or known to have coronary artery disease. MR angiograms were compared with those obtained with retrospective respiratory gating. Of 52 main coronary arteries, 47 could be visualized with the breath-hold technique and 49 with the gating technique. Signal-to-noise and contrast-to-noise ratios were significantly higher with the breath-hold technique. Overall image quality was slightly lower with breath-hold imaging. With either technique, three of five, significant coronary stenoses were correctly identified.

Contrast Media↗

Bed rest in deep vein thrombosis and the incidence of scintigraphic pulmonary embolism.

In several countries of central Europe, patients with acute proximal deep vein thrombosis (DVT) are treated not only by anticoagulation and compression therapy but additionally by strict bed rest for 6-8 days. Until now the theoretical assumption that bed rest substantially reduces the incidence of pulmonary embolism has not been subjected to empirical verification. Patients with acute proximal DVT proven by ultrasonography were randomly assigned to strict bed rest for 8 days (treatment group) or to stay mobilised (control group). In both groups, basic treatment consisted in anticoagulation by subcutaneous low molecular weight heparin/vitamin-K-antagonist and compression therapy. The incidence of pulmonary embolism was assessed by serial ventilation/perfusion SPECT on day 1 and days 8-10. Of the 309 patients with proximal DVT considered for inclusion, 180 were excluded according to the study protocol, and 3 did not give informed consent. One hundred and twenty-six patients were randomly assigned to observe bed rest (n = 62) or to keep mobilised (n = 64). Four patients refused follow-up lung scan. A new lung perfusion defect was detected in 10/59 patients in the treatment group compared to 14/63 patients in the control group (one-sided p-value = 0.25; power 0.8). Bed rest as an additional measure in the treatment of DVT is not able to substantially reduce the incidence of scintigraphically detectable pulmonary embolism. The discomfort and costs associated with the prescription of bed rest in DVT are obviously inappropriate.

Adult↗

Value of electron-beam computed tomography for the noninvasive detection of high-grade coronary-artery stenoses and occlusions.

BACKGROUND: Reliable noninvasive assessment of coronary-artery stenoses and occlusions would constitute an advantage in the care of patients with known or suspected coronary artery disease. We investigated the accuracy of contrast-enhanced electron-beam computed tomography (CT) for the detection of high-grade coronary-artery stenoses and occlusions. METHODS: Electron-beam CT was performed in 125 patients. After intravenous injection of a contrast agent, 40 cross-sectional images of the heart were acquired during inspiration, triggered by the electrocardiogram in diastole. Three-dimensional reconstructions of the heart and coronary arteries were rendered to facilitate evaluation of the images. The proximal and middle segments of the major coronary arteries were evaluated for the presence or absence of high-grade stenoses and occlusions. The results were compared with those of invasive coronary angiography in a blinded fashion. RESULTS: Because of technical problems that impaired the quality of the images, 124 (25 percent) of the 500 coronary arteries studied (left main, left anterior descending, left circumflex, and right coronary) in a total of 125 patients were excluded from evaluation. No vessels could be evaluated in 19 patients (15 percent), and another 28 patients (22 percent) had one, two, or three vessels that could not be evaluated. In the remaining coronary arteries with adequate image quality, electron-beam CT permitted visualization of 69 of 75 high-grade stenoses and occlusions (sensitivity, 92 percent), whereas in 282 of 301 arteries, the absence of high-grade stenoses and occlusions was correctly detected (specificity, 94 percent). CONCLUSIONS: When image quality is adequate, electron-beam CT may be useful to detect or rule out high-grade coronary-artery stenoses and occlusions.

Adult↗