Georgios Gouvras, head of DG SANCO's health threats unit.
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Biomedical subjects
Publications and source records attributed to A Werner.
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Cationic lipid complexes have been shown to be bound and internalized selectively by angiogenic tumor endothelial cells after intravenous injection. Based on this phenomenon, the chemotherapeutic agent paclitaxel was encapsulated into these lipid complexes providing a vascular targeting agent (MBT-0206). As noninvasive imaging techniques are of critical importance for optimizing antivascular cancer treatment in the clinic, we have evaluated the antivascular effects of MBT-0206 in the A-MEL-3 solid tumor model using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Twenty-four hours after three intravenous applications of MBT-0206, tumors of treated animals demonstrated a significant decrease of intratumoral blood volume and an increase of vascular permeability in comparison to size-matched control tumors. In contrast, animals treated with conventional paclitaxel given as Taxol at equal drug dose did not show any significant differences in vascular parameters acquired by DCE-MRI in comparison to controls. Immunohistological analysis confirmed a significant reduction of microvessel density in MBT-0206 treated tumors. Moreover, a significant increase of intratumoral microvascular occlusion following MBT-0206 treatment was observed compared to controls and paclitaxel treated animals. In conclusion, antivascular tumor therapy with MBT-0206 significantly impairs functional tumor microcirculation. DCE-MRI is a promising tool to quantify the antivascular effects of MBT-0206 during treatment.
Adequate public health preparedness for bioterrorism includes the elaboration of an agreed list of biological and chemical agents that might be used in an attack or as threats of deliberate release. In the absence of counterterrorism intelligence information, public health authorities can also base their preparedness on the agents for which the national health structures would be most vulnerable. This article aims to describe a logical method and the characteristics of the variables to be brought in a weighing process to reach a priority list for preparedness. The European Union, in the aftermath of the anthrax events of October 2001 in the United States, set up a task force of experts from multiple member states to elaborate and implement a health security programme. One of the first tasks of this task force was to come up with a list of priority threats. The model, presented here, allows Web-based updates for newly identified agents and for the changes occurring in preventive measures for agents already listed. The same model also allows the identification of priority protection action areas.
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Foot pad dermatitis has been observed in turkeys, puppies and kittens fed diets deficient in methionine. Excess cystine aggravated the lesions and decreased body weight gain in puppies and turkeys. The objective of this study was to determine whether methionine deficiency induced perioral and foot pad lesions in kittens and whether excess cystine exacerbated the lesions. Eighteen kittens were divided into three groups and offered one of three diets: diet 1, low-methionine, low-cystine (LMLC; 1.6 g methionine and 1.6 g cystine/kg diet); diet 2, low-methionine, high-cystine (HMHC; 1.6 methionine and 15 g cystine/kg diet); diet 3, high-methionine, high-cystine (HMHC; 15 g methionine and 15 g cystine/kg diet). Kittens in the LMLC group lost body weight, whereas those in the LMHC group maintained their body weight and those in the HMHC group gained weight. Plasma methionine concentrations were significantly higher (p < 0.001) for the HMHC group than for the LMLC and LMHC groups. Plasma cyst(e)ine (sum of cysteine and cystine) concentrations were different (p < 0.001) among all the three groups. Two kittens given the LMLC diet developed mild perioral lesions. All kittens receiving the LMHC diet developed foot pad lesions and severe perioral lesions. Histopathological changes observed in perioral biopsy specimens were similar to those described in protein deficiency. In conclusion, the results showed that a diet severely deficient in methionine causes perioral lesions in kittens, and that addition of excess cystine to the diet aggravates the perioral lesions and also causes foot pad lesions.
Enhanced plasma heat conductivity in the presence of kinetic Alfvén waves (KAW) is predicted theoretically. The enhancement is shown to be strongest when the electron collision frequency exceeds the particle transit frequency in the wave field. Alfvén waves (both KAW and ideal MHD Alfvén eigenmodes generating the KAW) are studied in a shot of the Wendelstein 7-AS stellarator. On the basis of these results, strong thermal crashes observed during bursting Alfvénic activity in the mentioned shot are explained.
According to EC regulations the deliberate release of genetically modified (GM) crops into the agro-environment needs to be accompanied by environmental monitoring to detect potential adverse effects, e.g. unacceptable levels of gene flow from GM to non-GM crops, or adverse effects on single species or species groups thus reducing biodiversity. There is, however, considerable scientific and public debate on how GM crops should be monitored with sufficient accuracy, discussing questions of potential adverse effects, agro-environmental variables or indicators to be monitored and respective detection methods; Another basic component, the appropriate number and location of monitoring sites, is hardly considered. Currently, no consistent GM crop monitoring approach combines these components systematically. This study focuses on and integrates spatial agro-environmental aspects at a landscape level in order to design monitoring networks. Based on examples of environmental variables associated with the cropping of Bt-Maize (Zea maize L.), herbicide-tolerant (HT) winter oilseed rape (Brassica napus L.), HT sugar beet (Beta vulgaris L.), and starch-modified potato (Solanum tuberosum L.), we develop a transferable framework and assessment scheme that comprises anticipated adverse environmental effects, variables to be measured and monitoring methods. These we integrate with a rule-based GIS (geographic information system) analysis, applying widely available spatial area and point information from existing environmental networks. This is used to develop scenarios with optimised regional GM crop monitoring networks.
Since 1996, all citizens of the Federal Republic of Germany who are insured in the statutory health insurance system are entitled to switch their sickness fund. The rationale of this regulation was to strengthen elements of competition in this system in order to stimulate the sickness funds to improve the efficiency of health care and to respond to consumers' preferences. Simultaneously, to avoid the implicit incentives for sickness funds to engage in risk selection, a risk compensation mechanism was introduced, including as morbidity-related risk adjusters age, sex and incapacity to work. Based on the KORA survey S4 (1999/2001) we take the case of switching behaviour in the region of Augsburg, and analyse whether this risk adjustment scheme was working effectively. The results show that persons changing their sickness fund were characterised by a comparatively smaller burden of chronic diseases and by a less frequent utilization of inpatient health care. Under these conditions, differences in the contribution rates do not accurately reflect differences in the performance and efficiency of sickness funds. Moreover, the migration of good risk to sickness funds with favourable contribution rates threatens the principle of financial solidarity. Therefore, the system of risk equalisation has to be developed towards measuring the risk volume borne by the sickness funds more precisely than hitherto.
In a prospective, randomised study on the repair of tears of the rotator cuff we compared the clinical results of two suture techniques for which different suture materials were used. We prospectively randomised 100 patients with tears of the rotator cuff into two groups. Group 1 had transosseous repair with No. 3 Ethibond using modified Mason-Allen sutures and group 2 had transosseous repair with 1.0 mm polydioxanone cord using modified Kessler sutures. After 24 to 30 months the patients were evaluated clinically using the Constant score and by ultrasonography. Of the 100 patients, 92 completed the study. No significant statistical difference was seen between the two groups: Constant score, 91% vs 92%; rate of further tear, 18% vs 22%; and revision, 4% vs 4%. In cases of further tear the outcome in group 2 did not differ from that for the intact repairs (91% vs 91%), but in group 1 it was significantly worse (94% vs 77%, p = 0.005). Overall, seven patients had complications which required revision surgery, in four for pain (two in each group) and in three for infection (two in group 1 and one in group 2).
BACKGROUND: Adult aseptic osteonecrosis (ON) represents a clinical picture with unexplained etiology. Since curative treatment of this disease often succeeds only in the early stage, pain therapy plays an important role in the treatment process. METHOD: We compared established and novel treatment options for ON as well as our own results after i.v. administration of the prostacyclin analogue iloprost with corresponding studies in the literature. RESULTS: In addition to treatment with nonsteroidal antirheumatic agents and opioids, surgical "core decompression," vasoactive medications, and hyperbaric oxygenation are effective. Treatment with iloprost for 5 days resulted in highly significant pain reduction. CONCLUSION: Symptomatic treatment is indicated in all stages of ON and curative treatment in stage I and early stage II. In cases of disease progression in the large joints, early endoprosthetic replacement is indicated to avoid secondary damage. In addition to employing vasoactive substances, a further curative treatment approach could be the use of mesenchymal stem cells.
HYPOTHESIS: Myocardial perfusion can be analyzed by the first pass of Doppler intensity (DI) signals in the myocardium by myocardial contrast echocardiography with triggered power Doppler harmonic imaging (PDHI). METHODS AND RESULTS: DI versus time plots during 1:1 triggering was acquired during a mechanically standardized intravenous bolus application of Levovist (400 mg ml(-1); 3 ml min(-1)) at rest and during vasodilator stress with dipyridamole. Data were analyzed in 21 patients (pts) with normal coronary arteries and in 6 pts with left anterior descending artery (LAD) stenosis. Transthoracic distal LAD-flow velocities could be determined in 7 normal pts. At stress the DI wash-in rate and the DI plateau increased (3.14+/-0.3 versus 5.06+/-0.4 DI s(-1); 24.6+/-2.5 versus 30.8+/-1.8 DI, respectively). To analyze the effect of heart rate on the DI versus time plots investigations were performed in 7 additional controls at rest and during rapid pacing. Heart rates below 100 bpm did not disturb the DI kinetics at 1:1 triggering. CONCLUSIONS: Myocardial perfusion can be assessed by the analysis of the first pass DI kinetics using Levovist. The estimation of vasodilator response by PDHI seems to be an alternative to the determination of coronary flow reserve.
AIM: The initial diagnostics of acute diverticulitis of the sigmoid should render the correct diagnosis as well as assisting in the decision on the options of conservative or surgical treatment by ruling out or demonstrating complications. At present, sonography or computed tomography (CT) are the two competing diagnostic options. This study was designed to demonstrate that sonography could be used as the method of choice. METHOD: 63 patients with clinical suspicion of acute diverticulitis of the sigmoid were examined initially by sonography or CT in a prospective study. RESULTS: Sonography and CT showed a 97 % sensitivity and specificity for reaching the accurate and clinically plausible diagnosis. As to the demonstration of complications of the disease, sensitivity and specificity were comparably high for both diagnostic methods. CONCLUSIONS: Sonography can compete with the more complex CT examination and therefore represents the recommended primary diagnostic procedure.
UNLABELLED: We investigated the biocompatibility and osteogenetic potency of a porcine collagen I/III carrier in a human bone marrow and cord blood cell culture system. METHODS: Human mesenchymal mononuclear cells were isolated from cord blood and iliac crest bone marrow and cultivated in various cell densities on a semipermeable porcine collagen I/III carrier. After 14 days of in vitro cultivation both cultures were subjected to osteogenic stimulation by dexamethasone, ascorbic acid and beta-glycerol phosphate (DAG) until day 40. Semiquantitative immunochemical evaluation based on osteoblastic and progenitor cell markers was then done. RESULTS: With regard to the minimal local cell density required for growth and osteogenic differentiation, cord blood derived progenitor cells showed lower tolerance in comparison with bone marrow derived cells. For both cell culture systems three-dimensional growth and calcification within the collagen fibres were seen after osteogenic stimulation. CONCLUSION: Human cord blood and bone marrow derived mesenchymal stem cell are capable of differentiating into osteoblasts after incubation with a collagen I/III biomaterial.