3D printing in the planning and teaching of endovascular procedures.

BACKGROUND: The introduction of 3D printing in the medical field led to new possibilities in the planning of complex procedures, as well as new ways of training junior physicians. Especially in the field of vascular interventions, 3D printing has a wide range of applications. METHODOLOGICAL INNOVATIONS: 3D-printed models of aortic aneurysms can be used for procedural training of endovascular aortic repair (EVAR), which can help boost the physician's confidence in the procedure, leading to a better outcome for the patient. Furthermore, it allows for a better understanding of complex anatomies and pathologies. In addition to teaching applications, the field of pre-interventional planning benefits greatly from the addition of 3D printing. Especially in the preparation for a complex endovascular aortic repair, prior orientation and test implantation of the stent grafts can further improve outcomes and reduce complications. For both teaching and planning applications, high-quality imaging datasets are required that can be transferred into a digital 3D model and subsequently printed in 3D. Thick slice thickness or suboptimal contrast agent phase can reduce the overall detail of the digital model, possibly concealing crucial anatomical details. CONCLUSION: Based on the digital 3D model created for 3D printing, another new visualization technique might see future applications in the field of vascular interventions: virtual reality (VR). It enables the physician to quickly visualize a digital 3D model of the patient's anatomy in order to assess possible complications during endovascular repair. Due to the short transfer time from the radiological dataset into the VR, this technique might see use in emergency situations, where there is no time to wait for a printed model.

Protein-repellent and antimicrobial nanoparticle coatings from hyaluronic acid and a lysine-derived biocompatible surfactant.

Biofilm formation triggered by uncontrolled protein adsorption, on medical devices is the leading cause of catheter-associated urinary tract infections (CAUTI) during implantation. Herein, we report a water-based, green and one-step strategy to functionalize surfaces of silicone catheters, poly(dimethylsiloxane) (PDMS), with antifouling and antimicrobial substances to avoid uncontrolled protein adsorption and microbial attachment. A novel synergetic formulation consisting of an anionic glycosaminoglycan (hyaluronic acid, HA) and a lysine-derived biocompatible cationic surfactant (Nε-myristoyl-lysine methyl ester, MKM) was prepared, resulting in the formation of nanoparticles (NPs, ca. 100-250 nm). Besides their high stability and long-lasting hydrophilicity in ambient and aqueous environments for 60 days, the nanometric layers (48 ± 3 nm) of HA-MKM NPs on PDMS showed no adsorption of BSA and lysozyme and substantially lower adsorption of fibrinogen as revealed by a quartz crystal microbalance with dissipation (QCM-D). In vitro antimicrobial test with S. aureus, E. coli, P. aeruginosa, P. mirabilis, C. albicans microbes under dynamic conditions revealed that the microbial growth was hampered by 85% compared with unmodified PDMS. Given the multiple functionalities, charges and diverse physiochemical properties of polysaccharide-lysine-based surfactant mixtures, this approach can be easily extended to the development of novel coatings on other silicone-based materials, thereby broadening potential applicability of PDMS-based biomaterials/devices in microfluidics, diagnostic biosensors and others.

Selective immobilization and detection of DNA on biopolymer supports for the design of microarrays.

DNA immobilization for the manufacturing of microarrays requires sufficient probe density, low unspecific binding and high interaction efficiency with complementary strands that are detected from solutions. Many of these important parameters are affected by the surface chemistry and the blocking steps conducted during DNA spotting and hybridization. This work describes an alternative method to selectively immobilize probes and to detect DNA on biocompatible, hydrophilic cellulose coated supports with low unspecific binding, high selectivity and appropriate sensitivity. It takes advantage of a relatively selective adsorption of water soluble polysaccharides on a solid cellulose matrix. Single strands of DNA were conjugated to this soluble polysaccharide and subsequently micro-spotted on solid cellulose thin films that were coated on glass and polymer slides. This resulted in adsorptively bound DNA-probes that were used to detect complementary, labelled DNA strands with different lengths and sequences by hybridization. The interaction of the DNA-conjugates with cellulose surfaces and the selectivity of hybridization were investigated by a quartz crystal microbalance with dissipation monitoring (QCM-D) and fluorescence scanning. The method of non-covalent immobilization of DNA probes on an uncharged, non-reactive, hydrophilic support lowers the unspecific binding and the number of handling steps required to conduct the experiments for the detection of DNA on microarrays. Simultaneously selectivity, hybridization efficiency and detection limits are maintained.

Differences in integrity of white matter and changes with training in spelling impaired children: a diffusion tensor imaging study.

While the functional correlates of spelling impairment have been rarely investigated, to our knowledge no study exists regarding the structural characteristics of spelling impairment and potential changes with interventions. Using diffusion tensor imaging at 3.0 T, we here therefore sought to investigate (a) differences between children with poor spelling abilities (training group and waiting group) and controls, and (b) the effects of a morpheme-based spelling intervention in children with poor spelling abilities on DTI parameters. A baseline comparison of white matter indices revealed significant differences between controls and spelling-impaired children, mainly located in the right hemisphere (superior corona radiata (SCR), posterior limb of internal capsule, superior longitudinal fasciculus). After 5 weeks of training, spelling ability improved in the training group, along with increases in fractional anisotropy and decreases of radial diffusivity in the right hemisphere compared to controls. In addition, significantly higher decreases of mean diffusivity in the right SCR for the spelling-impaired training group compared to the waiting group were observed. Our results suggest that spelling impairment is associated with differences in white-matter integrity in the right hemisphere. We also provide first indications that white matter changes occur during successful training, but this needs to be more specifically addressed in future research.

[Methodological problems in the radioimmunologic measurement of ANP (atrial natriuretic peptide)]. / Methodische Probleme der radioimmunologischen ANP-Messung.

Parameters influencing the measurement of hANP are designated and discussed on the basis of data from the literature and from our own results. Plasma hANP is dependent on the anatomical location of blood withdrawal, posture, state of hydration and salt load and medications. Interfering substances contained in plasma, management of samples and the type of assay used are of utmost importance. Direct RIA of hANP appears to be particularly sensitive to interferences. Preextraction of hANP from EDTA plasma by octadecylsilica cartridges, followed by RIA seems to be the most trustworthy method for measurement of hANP. Nevertheless, with this method too, we obtain different values for identical plasma samples if we use different antisera. Additionally, lipemia significantly lowers the ascertainable amount of endogenous, but not of exogenously added alpha-hANP. Therefore, it is reasonable to conclude that in preextracted samples too, hANP is not a homogeneous species. We observe a time-dependent increase in plasma hANP, reaching a final stable plateau value (about three times the initial values) after about 1.5 h, if EDTA blood samples are left on ice for prolonged time. Hemolysis interferes significantly with hANP determination. Readings of hANP values are reduced in dependence on plasma haemoglobin concentration. According to our experience, EDTA plasma can be stored for several months in either lyophilized form or deep frozen at -20 degrees C without the risk of reduction of hANP immunoreactivity. The data presented in this paper clearly show, that measurement of hANP is susceptible to faults in several details. Results should therefore be viewed critically.

[Effects of treatment of arrhythmias requiring therapy in dilated cardiomyopathy with amiodarone on alpha human atrial natriuretic peptide]. / Auswirkungen der Behandlung therapiepflichtiger Arrhythmien bei dilatativer CMP mit Amiodaron auf das alpha-humane atriale natriuretische Peptid (alpha-hANP).

In a longitudinal study comprising a total of 18 patients, the paradoxical time course of hANP plasma levels, i.e. the reproducibility of the low levels previously reported in cases of extreme cardiac insufficiency after administration of amiodarone, was investigated over a period of 9 months. At the same time, the effect of the degree of cardiac insufficiency and arrhythmia on the secretion of hANP was observed. The patients had been admitted to hospital because of the diagnoses "cardiac insufficiency secondary to cardiomyopathy" or "Grade IVb arrhythmia according to Lown's classification". During in-patient treatment, antiarrhythmic therapy was commenced in all patients. Clinical examinations and determinations of humoral parameters during therapy showed a substantial number of patients, who exhibited no increase in hANP levels despite massive cardiac decompensation. As far as drug therapy of patients with severe arrhythmias secondary to congestive (dilated) cardiomyopathy is concerned, amiodarone has proved to be the drug of choice in combination with digitalis, ACE inhibitors and diuretics. There is a close correlation between the degree of cardiac insufficiency and plasma hANP levels.

Big-endothelin release in baboon bacteremia is partially TNF dependent.

Big-endothelin (big-ET) is one of the endothelium-derived vasoactive substances that plays an important role in regulating the vascular tone. Because the role of this agent in bacteremia remains unknown, we investigated whether bacteremia induces the release of big-ET in a subhuman primate model and whether tumor necrosis factor (TNF) is an important mediator of big-ET release. To study this, we infused 8 male baboons (17 to 19 kg body weight) intravenously for 2 hours with Escherichia coli (5 x 10(8) CFU/kg) and observed them for 72 hours. Plasma was obtained at various intervals and assayed for big-ET by using immunoassay. Four bacteremic animals given vehicle only showed a peak big-ET plasma concentration of 15.1 +/- 4.6 fmol/ml at 10 hours, as compared with a baseline concentration of 0.9 +/- 0.5 fmol/ml. Administration of anti-TNF monoclonal antibodies (CB6, 15 mg/kg) 2 hours before E. coli infusion in additional animals prevented the rise in plasma TNF levels (5.7 +/- 2.5 ng/ml versus nondetectable) and significantly (p < 0.01) attenuated the release of big-ET. Hemodynamic measurements revealed the typical pattern of sepsis, with generally more stable circulatory conditions in the anti-TNF-treated animals. Moreover, the mortality rate decreased from 100% to 0% with anti-TNF treatment. These studies, therefore, lead us to conclude that TNF, directly or indirectly through another mediator, plays an important role in the endothelin production/release during bacteremia and that neutralization of circulating TNF appears to be beneficial for improving the survival after bacteremia.