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188 Publications visible to you, out of a total of 188
Anesthesia management for transapical transcatheter aortic valve implantation: a case series
Genetical Statistics and Systems Biology

Abstract (Expand)

OBJECTIVE\backslashr\backslashnThe purpose of this study was to review the management of anesthesia for transapical transcatheter aortic valve implantation.\backslashr\backslashnDESIGN\backslashr\backslashnRetrospective … review of collected data.\backslashr\backslashnSETTING\backslashr\backslashnUniversity-affiliated heart center.\backslashr\backslashnPARTICIPANTS\backslashr\backslashnOne hundred consecutive patients with severe aortic stenosis.\backslashr\backslashnINTERVENTIONS\backslashr\backslashnGeneral anesthesia followed by an established fast-track protocol.\backslashr\backslashnMATERIALS AND METHODS\backslashr\backslashnA total of 100 patients with significant AS received transapical transcatheter aortic valve implantation. The patients were treated following a fast-track protocol. The mean arterial pressure was maintained above 65 mmHg by volume and/or inotropes during the procedure. The mean arterial pressure was increased above 75 mmHg to avoid hemodynamic deterioration before starting rapid ventricular pacing for the balloon valvuloplasty and the valve implantation. Transesophageal echocardiography was used to assess valve size and for hemodynamic monitoring. Eighty-one patients were treated completely off pump. There was a significant decline in mean arterial pressure from pre- to postvalvuloplasty (74.7 +/- 9.1 mmHg v 63.6 +/- 11.3 mmHg, p \textless 0.001) and from pre- to postimplantation (76.5 +/- 12.6 mmHg v 67.2 +/- 12.7, p \textless 0.001). The first 10 patients in the study intentionally were placed on cardiopulmonary bypass, and 9 patients required cardiopulmonary bypass because of hemodynamic deterioration.\backslashr\backslashnCONCLUSION\backslashr\backslashnA well-designed anesthetic plan as well as an understanding of the surgical procedure and the hemodynamic effects of rapid ventricular pacing are required to ensure successful outcomes in this new surgical option for high-risk patients.

Authors: Jens Fassl, Thomas Walther, Heinrich Volker Groesdonk, Joerg Kempfert, Michael Andrew Borger, Markus Scholz, Chirojit Mukherjee, Axel Linke, Gerhard Schuler, Friedrich Wilhelm Mohr, Joerg Ender

Date Published: 1st Jun 2009

Publication Type: Journal article

Antiphospholipidsyndrom und retinale venöse Verschlüsse. Metaanalyse publizierter Studien
Genetical Statistics and Systems Biology

Abstract (Expand)

The role of antiphospholipid syndrome (APS) in the pathogenesis of retinal vein occlusion has been discussed for several years. Conflicting results of the published studies are caused by small numbers … of investigated patients and lack of control groups. We performed a meta-analysis of all case-control studies published up to July 2007 that investigated the prevalence of APS according to current diagnostic criteria for this syndrome.The results of meta-analysis show a significantly higher prevalence of APS in patients with retinal vein occlusion compared with controls. Patients with APS are treated with anticoagulants to reduce the risk of recurrence of thrombosis. Therefore, screening for APS seems to be indicated in all patients with retinal vein occlusion, and, in the case of a positive result, initiation of anticoagulation. For patients with retinal vein occlusion with APS, no data are currently available regarding the recurrence of thrombosis. To give a clear recommendation, a prospective randomized study is required to investigate the benefit of anticoagulation.

Authors: Matus Rehak, M. Müller, Markus Scholz, J. Wiercinska, D. Niederwieser, Peter Wiedemann

Date Published: 1st May 2009

Publication Type: Journal article

Leipziger \textquotedblFast-track\textquotedbl-Protokoll in der Kardioanästhesie. Effektiv, sicher und ökonomisch sinnvoll
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND\backslashr\backslashnIn November 2005 a complex, multimodal anesthesia fast-track protocol (FTP) was introduced for elective cardiac surgery patients in the Cardiac Center of the University … of Leipzig which included changing from an opioid regime to remifentanil and postoperative treatment in a special post-anesthesia recovery and care unit. The goal was to speed up recovery times while maintaining safety and improving costs.\backslashr\backslashnMETHOD\backslashr\backslashnA total of 421 patients who underwent the FTP and were treated in the special recovery room were analyzed retrospectively. These patients were compared with patients who had been treated by a standard protocol (SP) prior to instituting the FTP. Primary outcomes were time to extubation, length of stay in the intensive care unit (ICU) and treatment costs.\backslashr\backslashnRESULTS\backslashr\backslashnThe times to extubation were significantly shorter in the FTP group with 75 min (range 45-110 min) compared to 900 min (range 600-1140 min) in the SP group. Intensive care unit stay and hospital length of stay were also significantly shorter in the FTP group (p\textless0.01). The reduction of treatment costs of intensive care for FTP patients was 53.5% corresponding to savings of EUR 738 per patient in the FTP group compared with the SP group.\backslashr\backslashnCONCLUSIONS\backslashr\backslashnThe Leipzig fast-track protocol for cardio-anesthesia including the central elements of switching opiate therapy to remifentanil and switching patient recovery to a special post-anesthesia recovery and care unit, shortened therapy times, is safe and economically effective. BACKGROUND In November 2005 a complex, multimodal anesthesia fast-track protocol (FTP) was introduced for elective cardiac surgery patients in the Cardiac Center of the University of Leipzig which included changing from an opioid regime to remifentanil and postoperative treatment in a special post-anesthesia recovery and care unit. The goal was to speed up recovery times while maintaining safety and improving costs. METHOD A total of 421 patients who underwent the FTP and were treated in the special recovery room were analyzed retrospectively. These patients were compared with patients who had been treated by a standard protocol (SP) prior to instituting the FTP. Primary outcomes were time to extubation, length of stay in the intensive care unit (ICU) and treatment costs. RESULTS The times to extubation were significantly shorter in the FTP group with 75 min (range 45-110 min) compared to 900 min (range 600-1140 min) in the SP group. Intensive care unit stay and hospital length of stay were also significantly shorter in the FTP group (p\textless0.01). The reduction of treatment costs of intensive care for FTP patients was 53.5% corresponding to savings of EUR 738 per patient in the FTP group compared with the SP group. CONCLUSIONS The Leipzig fast-track protocol for cardio-anesthesia including the central elements of switching opiate therapy to remifentanil and switching patient recovery to a special post-anesthesia recovery and care unit, shortened therapy times, is safe and economically effective.

Authors: D. Häntschel, Jens Fassl, Markus Scholz, Marcus Sommer, Anne-Kathrin Funkat, M. Wittmann, Joerg Ender

Date Published: 1st Apr 2009

Publication Type: Journal article

Association of MICA with rheumatoid arthritis independent of known HLA-DRB1 risk alleles in a family-based and a case control study
Genetical Statistics and Systems Biology

Abstract (Expand)

INTRODUCTION\backslashr\backslashnThe gene MICA encodes the protein major histocompatibility complex class I polypeptide-related sequence A. It is expressed in synovium of patients with rheumatoid … arthritis (RA) and its implication in autoimmunity is discussed. We analyzed the association of genetic variants of MICA with susceptibility to RA.\backslashr\backslashnMETHODS\backslashr\backslashnInitially, 300 French Caucasian individuals belonging to 100 RA trio families were studied. An additional 100 independent RA trio families and a German Caucasian case-control cohort (90/182 individuals) were available for replication. As MICA is situated in proximity to known risk alleles of the HLA-DRB1 locus, our analysis accounted for linkage disequilibrium either by analyzing the subgroup consisting of parents not carrying HLA-DRB1 risk alleles with transmission disequilibrium test (TDT) or by implementing a regression model including all available data. Analysis included a microsatellite polymorphism (GCT)n and single-nucleotide polymorphisms (SNPs) rs3763288 and rs1051794.\backslashr\backslashnRESULTS\backslashr\backslashnIn contrast to the other investigated polymorphisms, the non-synonymously coding SNP MICA-250 (rs1051794, Lys196Glu) was strongly associated in the first family cohort (TDT: P = 0.014; regression model: odds ratio [OR] 0.46, 95% confidence interval [CI] 0.25 to 0.82, P = 0.007). Although the replication family sample showed only a trend, combined family data remained consistent with the hypothesis of MICA-250 association independent from shared epitope (SE) alleles (TDT: P = 0.027; regression model: OR 0.56, 95% CI 0.38 to 0.83, P = 0.003). We also replicated the protective association of MICA-250A within a German Caucasian cohort (OR 0.31, 95% CI 0.1 to 0.7, P = 0.005; regression model: OR 0.6, 95% CI 0.37 to 0.96, P = 0.032). We showed complete linkage disequilibrium of MICA-250 (D’ = 1, r2= 1) with the functional MICA variant rs1051792 (D’ = 1, r2= 1). As rs1051792 confers differential allelic affinity of MICA to the receptor NKG2D, this provides a possible functional explanation for the observed association.\backslashr\backslashnCONCLUSIONS\backslashr\backslashnWe present evidence for linkage and association of MICA-250 (rs1051794) with RA independent of known HLA-DRB1 risk alleles, suggesting MICA as an RA susceptibility gene. However, more studies within other populations are necessary to prove the general relevance of this polymorphism for RA.

Authors: Holger Kirsten, Elisabeth Petit-Teixeira, Markus Scholz, Dirk Hasenclever, Helene Hantmann, Dirk Heider, Ulf Wagner, Ulrich Sack, Vitor Hugo Teixeira, Bernard Prum, Jana Burkhardt, Céline Pierlot, Frank Emmrich, François Cornelis, Peter Ahnert

Date Published: 2009

Publication Type: Journal article

Effectiveness of cytopenia prophylaxis for different filgrastim and pegfilgrastim schedules in a chemotherapy mouse model
Genetical Statistics and Systems Biology

Abstract (Expand)

OBJECTIVES Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is widely used to treat neutropenia during cytotoxic chemotherapy. The optimal scheduling of rhG-CSF is unknown and can …n hardly be tested in clinical studies due to numerous therapy parameters affecting outcome (chemotherapeutic regimen, rhG-CSF schedules, individual covariables). Motivated by biomathematical model simulations, we aim to investigate different rhG-CSF schedules in a preclinical chemotherapy mouse model. METHODS The time course of hematotoxicity was studied in CD-1 mice after cyclophosphamide (CP) administration. Filgrastim was applied concomitantly in a 2 x 3-factorial design of two dosing options (2 x 20 mug and 4 x 10 mug) and three timing options (directly, one, and two days after CP). Alternatively, a single dose of 40 mug pegfilgrastim was applied at the three timing options. The resulting cytopenia was compared among the schedules. RESULTS Dosing and timing had a significant influence on the effectiveness of filgrastim schedules whereas for pegfilgrastim the timing effect was irrelevant. The best filgrastim and pegfilgrastim schedules exhibited equivalent toxicity. Monocytes dynamics performed analogously to granulocytes. All schedules showed roughly the same lymphotoxicity. CONCLUSION We conclude that effectiveness of filgrastim application depends heavily on its scheduling during chemotherapy. There is an optimum of timing. Dose splitting is better than concentrated applications. Effectiveness of pegfilgrastim is less dependent on timing. OBJECTIVES Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is widely used to treat neutropenia during cytotoxic chemotherapy. The optimal scheduling of rhG-CSF is unknown and can hardly be tested in clinical studies due to numerous therapy parameters affecting outcome (chemotherapeutic regimen, rhG-CSF schedules, individual covariables). Motivated by biomathematical model simulations, we aim to investigate different rhG-CSF schedules in a preclinical chemotherapy mouse model. METHODS The time course of hematotoxicity was studied in CD-1 mice after cyclophosphamide (CP) administration. Filgrastim was applied concomitantly in a 2 x 3-factorial design of two dosing options (2 x 20 mug and 4 x 10 mug) and three timing options (directly, one, and two days after CP). Alternatively, a single dose of 40 mug pegfilgrastim was applied at the three timing options. The resulting cytopenia was compared among the schedules. RESULTS Dosing and timing had a significant influence on the effectiveness of filgrastim schedules whereas for pegfilgrastim the timing effect was irrelevant. The best filgrastim and pegfilgrastim schedules exhibited equivalent toxicity. Monocytes dynamics performed analogously to granulocytes. All schedules showed roughly the same lymphotoxicity. CONCLUSION We conclude that effectiveness of filgrastim application depends heavily on its scheduling during chemotherapy. There is an optimum of timing. Dose splitting is better than concentrated applications. Effectiveness of pegfilgrastim is less dependent on timing.

Authors: Markus Scholz, Manuela Ackermann, Frank Emmrich, Markus Loeffler, Manja Kamprad

Date Published: 2009

Publication Type: Journal article

Neuronal hypoxia in vitro: investigation of therapeutic principles of HUCB-MNC and CD133+ stem cells
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND\backslashr\backslashnThe therapeutic capacity of human umbilical cord blood mononuclear cells (HUCB-MNC) and stem cells derived thereof is documented in animal models of focal cerebral … ischemia, while mechanisms behind the reduction of lesion size and the observed improvement of behavioral skills still remain poorly understood.\backslashr\backslashnMETHODS\backslashr\backslashnA human in vitro model of neuronal hypoxia was used to address the impact of total HUCB-MNC (tMNC), a stem cell enriched fraction (CD133+, 97.38% CD133-positive cells) and a stem cell depleted fraction (CD133-, 0.06% CD133-positive cells) of HUCB-MNC by either direct or indirect co-cultivation with post-hypoxic neuronal cells (differentiated SH-SY5Y). Over three days, development of apoptosis and necrosis of neuronal cells, chemotaxis of MNC and production of chemokines (CCL2, CCL3, CCL5, CXCL8, CXCL9) and growth factors (G-CSF, GM-CSF, VEGF, bFGF) were analyzed using fluorescence microscopy, FACS and cytometric bead array.\backslashr\backslashnRESULTS\backslashr\backslashntMNC, CD133+ and surprisingly CD133- reduced neuronal apoptosis in direct co-cultivations significantly to levels in the range of normoxic controls (7% +/- 3%). Untreated post-hypoxic control cultures showed apoptosis rates of 85% +/- 11%. tMNC actively migrated towards injured neuronal cells. Both co-cultivation types using tMNC or CD133- reduced apoptosis comparably. CD133- produced high concentrations of CCL3 and neuroprotective G-CSF within indirect co-cultures. Soluble factors produced by CD133+ cells were not detectable in direct co-cultures.\backslashr\backslashnCONCLUSION\backslashr\backslashnOur data show that heterogeneous tMNC and even CD133-depleted fractions have the capability not only to reduce apoptosis in neuronal cells but also to trigger the retaining of neuronal phenotypes. BACKGROUND The therapeutic capacity of human umbilical cord blood mononuclear cells (HUCB-MNC) and stem cells derived thereof is documented in animal models of focal cerebral ischemia, while mechanisms behind the reduction of lesion size and the observed improvement of behavioral skills still remain poorly understood. METHODS A human in vitro model of neuronal hypoxia was used to address the impact of total HUCB-MNC (tMNC), a stem cell enriched fraction (CD133+, 97.38% CD133-positive cells) and a stem cell depleted fraction (CD133-, 0.06% CD133-positive cells) of HUCB-MNC by either direct or indirect co-cultivation with post-hypoxic neuronal cells (differentiated SH-SY5Y). Over three days, development of apoptosis and necrosis of neuronal cells, chemotaxis of MNC and production of chemokines (CCL2, CCL3, CCL5, CXCL8, CXCL9) and growth factors (G-CSF, GM-CSF, VEGF, bFGF) were analyzed using fluorescence microscopy, FACS and cytometric bead array. RESULTS tMNC, CD133+ and surprisingly CD133- reduced neuronal apoptosis in direct co-cultivations significantly to levels in the range of normoxic controls (7% +/- 3%). Untreated post-hypoxic control cultures showed apoptosis rates of 85% +/- 11%. tMNC actively migrated towards injured neuronal cells. Both co-cultivation types using tMNC or CD133- reduced apoptosis comparably. CD133- produced high concentrations of CCL3 and neuroprotective G-CSF within indirect co-cultures. Soluble factors produced by CD133+ cells were not detectable in direct co-cultures. CONCLUSION Our data show that heterogeneous tMNC and even CD133-depleted fractions have the capability not only to reduce apoptosis in neuronal cells but also to trigger the retaining of neuronal phenotypes.

Authors: Doreen M. Reich, Susann Hau, Tobias Stahl, Markus Scholz, Wilfried Naumann, Frank Emmrich, Johannes Boltze, Manja Kamprad

Date Published: 1st Dec 2008

Publication Type: Journal article

The prevalence of activated protein C (APC) resistance and factor V Leiden is significantly higher in patients with retinal vein occlusion without general risk factors. Case-control study and meta-analysis.
Genetical Statistics and Systems Biology

Abstract (Expand)

Several small case-control studies have investigated whether factor V Leiden (FVL) is a risk factor for retinal vein occlusion (RVO) and generated conflicting data. To clarify this question we performed … a large two-centre case-control study and a meta-analysis of published studies. Two hundred seven consecutive patients with RVO and a control group of 150 subjects were screened between 1996 and 2006. A systematic meta-analysis was done combining our study with further 17 published European case-control studies. APC resistance was detected in 16 out of 207 (7.7%) patients and eight out of 150 (5.3%) controls. The odds ratio (OR) estimated was 1.49 with a (non-significant) 95% confidence interval (CI) of 0.62-3.57. The meta-analysis including 18 studies with a total of 1,748 patients and 2,716 controls showed a significantly higher prevalence of FVL in patients with RVO compared to healthy controls (combined OR 1.66; 95% CI 1.19-2.32). All single studies combined in the meta-analysis were too small to reliably detect the effect individually. This explains the seemingly contradictory data in the literature. In conclusion, the prevalence of APC resistance (and FVL) is increased in patients with RVO compared to controls, but the effect is only moderate. Therefore, there is no indication for general screening of factor V mutation in all patients with RVO. We recommend this test to be performed in patients older than 50 years with an additional history of thromboembolic event and in younger patients without general risk factors like hypertension.

Authors: Matus Rehak, Jiri Rehak, Marc Müller, Susanne Faude, Frank Faude, Annelie Siegemund, Vera Krcova, Ludek Slavik, Dirk Hasenclever, Markus Scholz, Peter Wiedemann

Date Published: 9th Apr 2008

Publication Type: Journal article

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