Role of EDRF in the Regulation of Shear Rate in Large Coronary Arteries in Conscious Dogs

To determine whether dilation of large coronary arteries normalizes shear during increased flow following brief occlusion, six dogs were instrumented to measure aortic and left ventricular pressures, left circumflex coronary artery external diameter, and coronary blood flow. The coronary artery was occluded for 15 or 30 s. Data were obtained before and after blockade of EDRF synthesis with nitro-L-arginine. Internal coronary artery diameter and wall shear were calculated on a moment-to-moment basis and the area under the flow curve was measured. Peak flow and shear rate were unaffected by NLA or by the occlusion duration. Flow curve area increased with the duration of occlusion. Internal and external diameters increased significantly for 15 s occlusions before NLA (by 4 ± 1% in external diameter and by 11 ± 4% in internal diameter) and for 30 s occlusions before NLA (by 5 ± 1% in external diameter and by 14 ± 5% in internal diameter) but not after NLA. Adenosine infusions of 0.05, 0.10, 0.50, and 1.0 μmol/kg/min were also used to dilate the coronary arteries. With each infusion, flow, shear and diameter were allowed to reach steady state. Steady state shear was reduced only slightly and did not approach the baseline state. We conclude that increased shear rate causes an increase in coronary artery diameter which is EDRF dependent. Increased coronary artery diameter during reactive hyperemia and adenosine infusions did not normalize wall shear.     

Comparison of microscopy and radiography as gold standards in radiographic caries diagnosis

OBJECTIVES: To compare the effect of the choice of gold standard on the diagnostic outcome of approximal caries detection in original and compressed digital radiographs. METHODS: 116 extracted teeth radiographed with a storage phosphor system constituted the original images. These images were compressed at 1:20 and 1:33 with the JPEG irreversible compression standard. Five radiologists scored the three sets of images for the presence of approximal caries on a five-rank confidence scale. The radiographic scores were validated by stereomicroscopy (the true gold standard). The individual ROC areas for the five observers were used to select the worst (obsworst) and the best (obsbest) performer: Their scores in the original images were used as the second and third 'gold standards' for the remaining observers. Mean ROC areas for the three observers with the three types of images were calculated using these two new 'gold standards'. Differences between the ROC areas when using microscopy, obsworst, and obsbest as the 'gold standard' were compared. RESULTS: The mean ROC areas in the original images were 0.66, 0.74 and 0.91 using the true gold standard and obsbest and obsworst as the 'gold standards' respectively. The difference between the true gold standard and obsworst was statistically significant (P < 0.001). The mean ROC areas using the true gold standard decreased with increasing compression whereas they were constant or increased using obsworst and obsbest as 'gold standards', respectively. CONCLUSIONS: Accuracy in approximal caries diagnosis was significantly higher when an observer was the 'gold standard' than when the true gold standard was obtained by microscopy. Paradoxically, the compressed, degraded images were more accurate than the originals when an observer was the 'gold standard' while they were less accurate with the true gold standard. Thus, results obtained using observers' scores from the radiographs which are being evaluated, as validation for the presence of caries may mislead the clinician.     

Bekämpfung—Organisation—Behandlungserfolge (Statistik 2)

Ohne Zusammenfassung     

Hormone,Vitamine

Ohne Zusammenfassung     

Bekämpfung-Organisation-Behandlungserfolge (Statistik 2)

Ohne Zusammenfassung     

Biologie

Ohne Zusammenfassung     

Magnetresonanztomographie

More than any other lung imaging modality, magnetic resonance imaging (MRI) comprises morphologic and functional imaging aspects in a single examination. In practice, its application is facilitated by dedicated protocols for typical clinical questions and easy handling (e.g. no ECG trigger). The sensitivity of the basic protocol for infiltrates and lung nodules is almost equal to CT. Excellent soft tissue contrast facilitates tumour staging, e.g. the differentiation of tumour and atelectasis and the diagnosis of mediastinal and chest wall masses. Administration of contrast material contributes to detection of tumour necrosis and pleural reaction/carcinosis. Dynamic contrast-enhanced MRI and visualization of respiratory motion contribute functional information. For the diagnosis of pulmonary embolism, an initial, free breathing and non-contrast-enhanced examination for quick detection in case of severe embolism is combined with dynamic contrast-enhanced perfusion imaging, a high-resolution angiogram and a final 3D breath-hold acquisition. With these customized protocols, lung MRI offers not only solutions for tricky problems of daily routine, in particular for imaging the mediastinum. It is as well a good option for paediatrics and science or any situation where any radiation exposure or administration of CT contrast material would be contraindicated.     

Impaired nitric oxide modulation of myocardial oxygen consumption in genetically cardiomyopathic hamsters

We investigated the role of kinin and nitric oxide (NO) in the modulation of cardiac O(2)consumption in Syrian hamsters with overt heart failure (HF) and age-matched normal hamsters. Using echocardiography, the hamsters with heart failure had reduced ejection fraction [31(+/-8) v 76(+/-5)%] and LV dilation [4.9(+/-0. 2) v 5.7(+/-0.3) mm, both P<0.05 from normal]. O(2)consumption in the left ventricular free wall was measured using a Clark-type O(2)electrode in an air-tight chamber, containing Krebs solution buffered with Hepes (37 degrees C, pH 7.4). Concentration response curves to bradykinin (BK), ramiprilat (RAM), amlodipine (AMLO) and the NO donor, S -nitroso- N -acetyl-penicillamine (SNAP) were performed. Basal myocardial O(2)consumption was lower in the HF group compared to normal [316(+/-21) v 404(+/-36) nmol O(2)/min/g, respectively, P<0.05]. In the hearts from normal hamsters BK (10(-4)mol/l), RAM (10(-4)mol/l), and AMLO (10(-5)mol/l) all significantly reduced myocardial O(2)consumption by 42(+/-6)%, 29(+/-7)% and 27(+/-5)% respectively. This reduction was attenuated in the presence of N -nitro- l -arginine methyl ester (l -NAME) [BK: 3.3(+/-1.5)%, RAM: 3.3(+/-1.2)%, AMLO: 2.3(+/-1.2)%, P<0.05]. Interestingly in the hearts from HF group, BK, RAM and AMLO caused a significantly smaller reduction in myocardial O(2)consumption [10(+/-2)%, 2.5(+/-1.3)%, 6.3(+/-2.3)%, P<0.05]. In contrast, the NO donor SNAP reduced myocardial O(2)consumption in both groups and all those responses were not affected by l -NAME. These data indicate that endogenous NO production through the kinin-dependent mechanism is impaired at end-stage heart failure. The loss of kinin and NO control of mitochondrial respiration may contribute to the pathogenesis of heart failure.     

Myocardial glucose uptake is regulated by nitric oxide via endothelial nitric oxide synthase in Langendorff mouse heart

Although the role of nitric oxide (NO) in the modulation of vascular tone has been studied and well understood, its potential role in the control of myocardial metabolism is only recently evident. Several lines of evidence indicate that NO regulates myocardial glucose metabolism; however, the details and mechanisms responsible are still unknown. The aim of this study was to further define the role of NO in the control of myocardial glucose metabolism and the nitric oxide synthase (NOS) isoform responsible using transgenic animals lacking endothelial NOS (ecNOS). In the present study, we examined the regulation of myocardial glucose uptake using isometrically contracting Langendorff-perfused hearts from normal mice (C57BL/6J), mice with defects in the expression of ecNOS [ecNOS (-/-)], and its heterozygote [ecNOS (+/-)], and wild-type mice [ecNOS (+/+)] (n=6, respectively). In hearts from normal mice, little myocardial glucose uptake was observed. This myocardial glucose uptake increased significantly in the presence of N(omega)-nitro-L-arginine methyl ester (L-NAME). Similarly, in the hearts from ecNOS (-/-), glucose uptake was much greater than in normal mice, whereas myocardial glucose uptake of ecNOS (+/-) and ecNOS (+/+) mice was not different from normal mice. In addition, myocardial glucose uptake of ecNOS (+/-) and ecNOS (+/+) mice increased significantly in the presence of L-NAME. At a workload of 800 g. beats/min, L-NAME increased glucose uptake from 0.1+/-0.1 to 3+/-0.4 microg/min x mg in ecNOS (+/-) mice and from 0.2+/-0.1 to 2.7+/-0.7 microg/min x mg in ecNOS (+/+) mice. Furthermore, in the hearts from ecNOS (-/-) mice, 8-bromoguanosine 3':5'-cyclic monophosphate (8-Br-cGMP), a cGMP analog or S-nitroso-N-acetylpenicillamine (SNAP), a NO donor essentially shut off glucose uptake, and in hearts from ecNOS (+/-) mice, 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ), an inhibitor of cGMP, increased the glucose uptake significantly. These results indicate clearly that cardiac NO production regulates myocardial glucose uptake via a cGMP-dependent mechanism and strongly suggest that ecNOS plays a pivotal role in this regulation. These findings may be important in the understanding of the pathogenesis of the diseases such as ischemic heart disease, heart failure, diabetes mellitus, hypertension, and hypercholesterolemia, in which NO synthesis is altered and substrate utilization by the heart changes.