Volker Diehl, 60 Jahre

Ohne Zusammenfassung     

Early diagnosis of acute postoperative renal transplant rejection by indium-111-labeled platelet scintigraphy

A prospective evaluation of 111In-labeled platelet scintigraphy (IPS) for the early diagnosis of acute postoperative renal transplant rejection (TR) was undertaken. The results of IPS were compared with in vitro biochemical tests, the clinical finding of graft tenderness, and combined [99mTc]DTPA and [131I]orthoiodohippurate scintigraphy. With a sensitivity of 0.93 and a specificity of 0.95, IPS provided otherwise unavailable diagnostic information. Furthermore, postoperative IPS was a good predictor of long-term allograft survival.     

New Biological and Clinical Roles for the n–6 and n–3 Fatty Acids

Four new findings of the biochemistry and biology of the essential n–6 and n–3 fatty acids have recently been demonstrated. These findings will augment current knowledge as to the role of the essential fatty acids in human health.     

Quantifying the intra- and extravascular contributions to spin-echo fMRI at 3 T.

Functional MRI (fMRI) by means of spin-echo (SE) techniques provides an interesting alternative to gradient-echo methods because the contrast is based primarily on dynamic averaging associated with the blood oxygenation level-dependent (BOLD) effect. In this article the contributions from different brain compartments to BOLD signal changes in SE echo planar imaging (EPI) are investigated. To gain a better understanding of the underlying mechanisms that cause the fMRI contrast, two experiments are presented: First, the intravascular contribution is decomposed into two fractions with different regimes of flow by means of diffusion-weighting gradient schemes which are either flow-compensated, or will maximally dephase moving spins. Second, contributions from the intra- and extravascular space are selectively suppressed by combining flow-weighting with additional refocusing pulses. The results indicate two qualitatively different components of flowing blood which contribute to the BOLD contrast and a nearly equal share in functional signal from the intra- and extravascular compartments at TE approximately 80 ms and 3 T. Combining these results, there is evidence that at least one-half of the functional signal originates from the parenchyma in SE fMRI at 3 T. The authors suggest the use of flow-compensated diffusion weighting for SE fMRI to improve the sensitivity to the parenchyma.     

Characterization of 18F-FDG uptake in human endothelial cells in vitro.

The contribution of (18)F-FDG uptake by endothelial cells to uptake values measured by PET in various tissues is as yet unclear. We therefore sought to characterize (18)F-FDG uptake in an in vitro model of human endothelial cells. METHODS: Commercially obtained human umbilical vein endothelial cells (HUVECs) were seeded in 6-multiwell plates 48-96 h before incubation with 1-2 MBq (18)F-FDG per well. Radioactivity measurements were performed after washing and mechanical dissolvation of the cellular monolayers. Cellular (18)F-FDG uptake was referred to protein concentration. This experimental protocol was subsequently varied to study the effect of different parameters of interest. Furthermore, radio-thin-layer chromatography was used to identify intracellular (18)F-FDG metabolites. (18)F-FDG uptake in HUVECs was compared with that by a human monocyte-macrophage (HMM) preparation and by glioblastoma cells (GLIOs) under identical experimental conditions. RESULTS: (18)F-FDG accumulated in HUVECs in a time-dependent manner and was trapped mainly as (18)F-FDG-6-phosphate and (18)F-FDG-1,6-diphosphate. Unlabeled glucose and cytochalasin B competitively inhibited (18)F-FDG uptake, whereas phlorizin had no significant effect. Glucose deprivation significantly enhanced (18)F-FDG uptake by a factor of 2.7, whereas sodium depletion had no significant influence. HUVECs treated with vascular endothelial growth factor (VEGF) showed a significant 82% increase in (18)F-FDG accumulation after a 2-h exposure to 50 ng/mL VEGF. (18)F-FDG uptake in HUVECs was significantly higher than that in HMMs and in the range of the uptake values measured in GLIOs. CONCLUSION: (18)F-FDG accumulates in HUVECs by mechanisms analogous to those in neoplastic cells or neurons. VEGF significantly stimulates endothelial (18)F-FDG uptake. The observed differences in (18)F-FDG uptake between HUVECs, HMMs, and GLIOs are difficult to extrapolate to in vivo conditions but stimulate further studies on the contribution of endothelial (18)F-FDG uptake to the overall uptake of that tracer in neoplastic or vascular lesions.     

Incidence and Clinical Significance of Ventricular Late Potentials in Idiopathic Dilated Cardiomyopathy Compared to Coronary Artery Disease

Objective: This prospective study was designed to compare incidence and clinical significance of ventricular late potentials between patients with idiopathic dilated cardiomyopathy (IDC) and postinfarct patients (CAD) using exactly the same method of signal-averaged electrocardiography (SAECG) in both patient groups. Methods: Time-domain analysis of SAECG was performed in 120 consecutive patients with IDC, 120 patients with CAD, and 60 healthy controls. Ventricular late potentials were detected in 27 of 120 patients with IDC (23%) compared to 41 of 120 patients with CAD (34%; P < 0.05). Results: Ventricular late potentials were found in 2 of 60 controls (3%). During 15 ± 7 months follow-up, serious arrhythmic events occurred in 17 of 120 patients with IDC (14%) and in 13 of 120 patients with CAD (11%). The sensitivity of ventricular late potentials for future arrhythmic events was 35% for IDC compared to 77% for CAD (P < 0.05). The positive predictive value of late potentials detected by time-domain analysis was 22% for IDC versus 24% for CAD (P = ns). Conclusion: In this selected patient population with IDC and CAD, time-domain analysis of SAECG revealed a lower incidence of ventricular ate potentials in patients with IDC as compared to postinfarct patients. Whereas ventricular late potentials had a high sensitivity but a low positive predictive value for identification of postinfarct patients with serious arrhythmic events during follow-up, both sensitivity and positive predictive value of ventricular late potentials for future serious arrhythmic events were low in the setting of IDC.     

Potential diagnostic value of sampling oral mucosal surfaces for Actinobacillus actinomycetemcomitans in young adults*

Actinobacillus actinomycetemcomitans has been implicated in the pathogenesis of several forms of early onset and refractory adult periodontitis. Early diagnosis of colonization of the oral cavity might be of importance in order to initiate preventive measures. The aim of the present study was to determine the potential diagnostic value of oral mucosal and salivary tests to identify, among healthy young men with no or minor periodontal disease, individuals colonized by A. actinomycetemcomitans. Two hundred and one male recruits. 18–25 yr of age, took part in the present study. Mean values of periodontal parameters suggested only minor periodontal disease. Of the sites, 64.8±17.6% (mean ± SD) had a periodonta) probing depth (PPD) of 1 or 2 mm. only 1.6±2.9% deep sites of 5 mm were detected. More than 1000 subgingival and extracrevicular samples were selectively cultivated for A. actinomycetemcomitans. The organism was isolated in 55 subjects (21%). The odds for presence of at least 1 deep site of 5 mm was increased by a factor 1.99 if A. actinomycetemcomitans could be recovered. In identifying subjects colonized by A. actinomycetemcomitans. diagnostic test parameters sensitivity and predictive value for a negative test were 74.5±5.9% and 91.1±2.3%', respectively, for both saliva and dorsum of tongue samples. In contrast, pooled subgingival plaque from mesial surfaces of 1st molars was only 34.5±6.4% sensitive: the negative predictive value was 80.2±3.0%. The results point to a high diagnostic value of oral mucosal and especially saliva samples to identify young adult individuals colonized by A. actinomycetemcomitans.     

Pharmacokinetics of the enantiomers of felodipine in the dog after oral and intravenous administration of a pseudoracemic mixture

1. A pseudoracemic mixture of deuterated (S)-felodipine and unlabelled (R)-felodipine was administered as single i.v. or oral doses to four dogs. Plasma concentrations of the enantiomers and their corresponding pyridine metabolites were determined by g.l.c.-mass spectrometry. 2. No isotope effects were observed after oral administration of equimolar amounts of deuterated and unlabelled (S)-felodipine. 3. The pharmacokinetic parameters of the enantiomers were similar after i.v. administration, indicating that the disposition of felodipine was not stereoselective. 4. After oral administration the bioavailability of (R)-felodipine was slightly higher than that of (S)-felodipine in two of the dogs, presumably due to a lower first-pass extraction of the (R)-enantiomer, while no difference was observed in the other two dogs. 5. No substantial differences in Cmax or AUC were observed between the deuterated and unlabelled pyridine metabolites, indicating that the oxidative clearances of the felodipine enantiomers were similar.