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Frankfurt am Main, Germany

Nagele U.,General Hospital Hall in Tirol | Walcher U.,General Hospital Hall in Tirol | Bader M.,Community Hospital Ebersberg | Herrmann T.,Hannover Medical School | And 2 more authors.
World Journal of Urology | Year: 2015

Introduction: Aim of this study was to investigate whether the combination of high-pressure irrigation inflow combined with simultaneous sensor-controlled suction could improve irrigation turnover without leading to high peak intrarenal pressure in small-calibre percutaneous instruments (SCPI). M + M: A MIP XS sheath (9.5 Fr. outer diameter and 8.5 Fr. inner diameter) and a 7.5-Fr. nephroscope (3-Fr. irrigation channel; MIP XS by Nagele, Karl Storz, Tuttlingen, Germany) was inserted into the collecting system of a non-perfused cadaveric porcine kidney, an 8-Fr. mono-J catheter was introduced through the ureter. Irrigation was performed using a pressure-controlled, combined irrigation/suction pump (Uromat E.A.S.I., Karl Storz, Tuttlingen, Germany) in either single-flow or continuous-flow (=combination of irrigation and suction) mode. Intrarenal pressure was measured and irrigation fluid turnover was measured by a cystometry catheter inserted trans-parenchymally into the renal pelvis. Pressure changes were recorded by a urodynamic workstation. Results: Applying pressure-controlled suction, irrigation fluid turnover could be increased by 5 % at an inflow pressure of 75 mmHg (80–84 ml/min) and 15 % at an inflow pressure of 110 mmHg (196–110 ml/min). Suction decreased the intrarenal pressure by 14 % at 75 mmHg (19–14.5 cm H2O) and 28 % at 110 mmHg inflow pressure (37–26.5 cm H2O). Conclusion: Although combination of pressure irrigation with sensor-controlled suction increases irrigation flow in SCPI, the intrarenal pressure could be reduced with combined suction via a transurethral mono-J catheter. This irrigation method in percutaneous surgery is called purging effect. © 2015, Springer-Verlag Berlin Heidelberg. Source

Abbas S.,University of Cologne | Ihle P.,University of Cologne | Harder S.,University Hospital Frankfurt Am Main | Schubert I.,University of Cologne
Thrombosis and Haemostasis | Year: 2014

There is major concern about coumarins interacting with various drug classes and increasing the risk of overanticoagulation. The aim of the study was to assess bleeding risk in patients with concurrent use of antibiotics and phenprocoumon, the most widely prescribed coumarin in many European countries. We conducted a nested-case-control study within a cohort of 513,338 incident and continuous phenprocoumon users ≥18 years of age using claims data of the statutory health insurance company AOK, covering 30% of the German population. Bleeding risk associated with current use of antibiotics for systemic use (antibacterials/antimycotics) was calculated using conditional logistic regression in 13,785 cases with a bleeding event and 55,140 risk-set sampling-matched controls. Bleeding risk associated with any antibacterial use in phenprocoumon users was significantly increased [odds ratio (OR) 2.37, 95% confidence interval (CI) 2.20-2.56]. The association was stronger for gastrointestinal than for cerebral bleeding (OR 2.09, 95% CI 1.84-2.38 and OR 1.34, 95% CI 1.03-1.74, respectively) and highest for other/unspecified bleeding (OR 2.92, 95% CI 2.62-3.26). Specific antibiotic classes were strongly associated with bleeding risk, e.g. cotrimoxazole (OR 3.86, 95% CI 3.08-4.84) and fluorquinolones (OR 3.13, 95% CI 2.74-3.59), among those highest for ofloxacin (OR 5.00, 95% CI 3.01-8.32). Combined use of phenprocoumon and antimycotics was not significantly associated with bleeding risk. Risk was not significantly modified by age (pint=0.25) or sex (pint=0.96). The association was stronger the closer the antibiotic exposure was to the bleeding event. Among continuous phenprocoumon users, antibiotics - particularly quinolones and cotrimoxazole - should be prescribed after careful consideration due to an increased bleeding risk. Close monitoring of international normalised ratio levels after prescription is recommended. © Schattauer 2014. Source

Abbas S.,University of Cologne | Ihle P.,University of Cologne | Harder S.,University Hospital Frankfurt Am Main | Schubert I.,University of Cologne
Pharmacoepidemiology and Drug Safety | Year: 2015

Purpose: Clinical trials and few observational studies report increased hyperkalemia risks in heart failure patients receiving aldosterone blockers in addition to standard therapy. The aim of this study is to assess the hyperkalemia risk and combined use of spironolactone and long-term ACE (angiotensin-converting enzyme) inhibitor/angiotensin receptor blocker (ARB) therapy for heart failure in a real-life setting of a heterogeneous population. Methods: Using claims data of the statutory health insurance fund AOK, covering 30% of the German population, we performed a nested case-control study in a cohort of heart failure patients receiving continuous ACE/ARB therapy (n=1,491,894). Hyperkalemia risk associated with concurrent use of spironolactone and ACE/ARB was calculated by conditional logistic regression in 1062 cases and 10,620 risk-set-sampling-matched controls. Results: Risk of hyperkalemia in heart failure patients was significantly associated with spironolactone use (odds ratio (OR) (95% confidence interval (CI))=13.59 (11.63-15.88) in all and 11.05 (8.67-14.08) in those with information on New York Heart Association (NYHA) stage of disease). In the NYHA subpopulation, higher risk estimates were observed in short-term as compared with long-term users (OR (95%CI)=13.00 (9.82-17.21) and 9.12 (6.78-12.26), respectively). Moreover, the association was stronger in older (≥70years of age) as compared with younger patients (<70years of age) (OR (95%CI)=12.32 (9.35-16.23) and 8.73 (5.05-15.08), respectively), although interaction was not significant (pinteraction=0.07). Conclusions: Hyperkalemia risk associated with combined use of spironolactone and ACE/ARB is much stronger in real-life practice than observed in clinical trials. Careful potassium level monitoring in concomitant users of spironolactone and ACE/ARB is necessary. © 2015 John Wiley & Sons, Ltd. Source

Hoelzer D.,University Hospital Frankfurt Am Main
Current Opinion in Oncology | Year: 2013

PURPOSE OF REVIEW: To describe the current new targeted therapy with monoclonal and bispecific antibodies in adult acute lymphoblastic leukemia (ALL), to improve response rates and outcome. RECENT FINDINGS: Blast cells in ALL express a variety of specific antigens, such as CD19, CD20, CD22, CD33 and CD52, and recently monoclonal antibodies (MoAbs) became available to target these antigens. The anti-CD20 MoAb rituximab has substantially improved the outcome in Burkitt lymphoma/leukemia, and is currently applied in de-novo B-precursor ALL. The MoAbs directed against CD22, linked to cytotoxic agents, either to calicheamicin (inotuzomab ozogamicin) or to plant or bacterial toxins (epratuzumab) are explored in refractory/relapsed childhood and adult ALL. Targeting CD19 is of great interest, as it is expressed in all B-lineage cells, including early precursors. The new bispecific antibody blinatumomab combines single chain antibodies to CD19 and CD3, and thereby T cells lyse the CD19 bearing B cells and is effective in patients with positive minimal residual disease (MRD) or refractory/relapsed ALL. SUMMARY: Antibody therapy in ALL is very promising, with high rate of complete remission and MRD-negativity in advanced ALL. It is currently explored in de-novo ALL to establish the best setting in combination with chemotherapy or even as a monotherapy. © 2013 Wolters Kluwer Health Lippincott Williams & Wilkins. Source

Vratskikh O.,Medical University of Vienna | Stiasny K.,Medical University of Vienna | Zlatkovic J.,Medical University of Vienna | Tsouchnikas G.,Medical University of Vienna | And 6 more authors.
PLoS Pathogens | Year: 2013

The live attenuated yellow fever (YF) vaccine has an excellent record of efficacy and one dose provides long-lasting immunity, which in many cases may last a lifetime. Vaccination stimulates strong innate and adaptive immune responses, and neutralizing antibodies are considered to be the major effectors that correlate with protection from disease. Similar to other flaviviruses, such antibodies are primarily induced by the viral envelope protein E, which consists of three distinct domains (DI, II, and III) and is presented at the surface of mature flavivirions in an icosahedral arrangement. In general, the dominance and individual variation of antibodies to different domains of viral surface proteins and their impact on neutralizing activity are aspects of humoral immunity that are not well understood. To gain insight into these phenomena, we established a platform of immunoassays using recombinant proteins and protein domains that allowed us to dissect and quantify fine specificities of the polyclonal antibody response after YF vaccination in a panel of 51 vaccinees as well as determine their contribution to virus neutralization by serum depletion analyses. Our data revealed a high degree of individual variation in antibody specificities present in post-vaccination sera and differences in the contribution of different antibody subsets to virus neutralization. Irrespective of individual variation, a substantial proportion of neutralizing activity appeared to be due to antibodies directed to complex quaternary epitopes displayed on the virion surface only but not on monomeric E. On the other hand, DIII-specific antibodies (presumed to have the highest neutralizing activity) as well as broadly flavivirus cross-reactive antibodies were absent or present at very low titers. These data provide new information on the fine specificity as well as variability of antibody responses after YF vaccination that are consistent with a strong influence of individual-specific factors on immunodominance in humoral immune responses. © 2013 Vratskikh et al. Source

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