Goltz J.P.,University of Würzburg |
Schmid J.S.,University of Würzburg |
Ritter C.O.,University of Würzburg |
Knodler P.,University of Würzburg |
And 4 more authors.
Journal of Vascular Access | Year: 2013
Purpose: To identify risk factors for the development of catheter-related thrombosis (CRT) in patients with totally implantable venous access ports (TIVAP) in the forearm, and to analyze the effect of prophylaxis and treatment. Methods: We retrospectively identified 200 patients (94 men, 106 women, mean age 57.7 +/-14 y) with TIVAP implantation in the forearm between 3/2010 and 11/2010. Type, number of punctures and sonographically defined diameter of the accessed vein were analyzed. Chemotherapy administered prior to the implantation procedure and history of thrombo-embolic events were assessed. Thrombo-embolic prophylaxis (TEP) following port implantation and treatment as well as course of CRT were analyzed. Results: Twenty-one patients (10.5%) were diagnosed with CRT. Accessed vessels and mean diameter were basilic (n=150, 3.7 mm), brachial (n=39, 3.5 mm) and cephalic (n=11, 3.5 mm) vein. Neither type nor vessel diameter had effect on CRT development (P>.05). Implantation in the left forearm resulted in a significantly higher rate of CRT (P=.04). Ninety-five patients (47.5%) received chemotherapy and 30 patients (15.0%) had a history of thrombosis prior to implantation; both had no effect on development of CRT. Low molecular weight heparin (LMWH) was prescribed in 94/200 patients (47.0%) and had no effect on development of CRT (P>.05). Therapeutic anticoagulation with LMWH resulted in clinical improvement in 12/21 patients (57.4%). Conclusions: TIVAPs of the forearm may be associated with a certain rate of early and late CRT. The simplest vein to puncture should be selected for vascular access. Thrombo-embolic prophylaxis appears to be rather ine ffective for prevention of CRT. © 2011 Wichtig Editore.
Zimprich A.,Medical University of Vienna |
Benet-Pages A.,Helmholtz Center for Environmental Research |
Struhal W.,Allgemeines Krankenhaus |
Graf E.,Helmholtz Center for Environmental Research |
And 35 more authors.
American Journal of Human Genetics | Year: 2011
To identify rare causal variants in late-onset Parkinson disease (PD), we investigated an Austrian family with 16 affected individuals by exome sequencing. We found a missense mutation, c.1858G>A (p.Asp620Asn), in the VPS35 gene in all seven affected family members who are alive. By screening additional PD cases, we saw the same variant cosegregating with the disease in an autosomal-dominant mode with high but incomplete penetrance in two further families with five and ten affected members, respectively. The mean age of onset in the affected individuals was 53 years. Genotyping showed that the shared haplotype extends across 65 kilobases around VPS35. Screening the entire VPS35 coding sequence in an additional 860 cases and 1014 controls revealed six further nonsynonymous missense variants. Three were only present in cases, two were only present in controls, and one was present in cases and controls. The familial mutation p.Asp620Asn and a further variant, c.1570C>T (p.Arg524Trp), detected in a sporadic PD case were predicted to be damaging by sequence-based and molecular-dynamics analyses. VPS35 is a component of the retromer complex and mediates retrograde transport between endosomes and the trans-Golgi network, and it has recently been found to be involved in Alzheimer disease. © 2011 by The American Society of Human Genetics. All rights reserved.
Hensel F.,Patrys GmbH |
Timmermann W.,Allgemeines Krankenhaus |
Von Rahden B.H.A.,University of Würzburg |
Rosenwald A.,University of Würzburg |
And 2 more authors.
Oncology Reports | Year: 2014
The fully human monoclonal antibody PAT-SC1 is specific for an isoform of CD55 (decay-accelerating factor) designated CD55PAT-SC1. This antigen is expressed in the majority (80%) of gastric cancers (GCs), and the antibody induces tumour cell-specific apoptosis in vitro as well as in vivo. PAT-SC1, therefore, has been deemed promising as a therapeutic agent. Here, we describe the results of an academic clinical study performed in a neoadjuvant setting with resectable GC patients. Patients undergoing treatment for GC between 1997 and 2001 were tested for CD55PAT-SC1 expression. Fifty-one resectable patients that tested positively received a single administration of 20 mg PAT-SC1 48 h prior to surgery. They underwent standard surgery with either subtotal or total gastrectomy with bursectomy, omentectomy and a modi- fied D2-lymphadenectomy, aimed at R0 resection. Primary endpoints of the present study were to evaluate side-effects of the PAT-SC1 antibody treatment and to evaluate histopathological effects such as tumour regression and induction of apoptosis. Long-term survival was a secondary endpoint. Administration of PAT-SC1 appeared safe with only reversible side-effects according to WHO grade I and II. Despite the low-dose of the antibody, 81.6% of the patients showed signs of increased apoptosis within the primary tumour and 60% showed signs of tumour cell regression. Comparison of the 10-year survival rates of the R0-resected CD55PAT-SC1-positive patients treated with the PAT-SC1 antibody with a historical collective of R0-resected CD55PAT-SC1- positive patients not treated with PAT-SC1 indicated a survival benefit in the treated patients. Furthermore, comparison of the patient survival of CD55 PAT-SC1-positive vs. CD55PAT-SC1-negative groups suggested that CD55PAT-SC1 antigen expression is an independent predictor of poor survival in a Cox regression analysis. Antibody PAT-SC1 may be a useful additive therapeutic agent in the treatment of patients with CD55 PAT-SC1-expressing GCs. In combination with radical standard surgery, PAT-SC1 given as an adjuvant or neoadjuvant immunotherapeutic agent induces apoptosis in tumour cells which may improve survival of these patients. Because of the human origin and its specific binding to the CD55PAT-SC1 antigen, PAT-SC1 was well tolerated in this trial.
Schoenfeld A.A.,Carl von Ossietzky University |
Schoenfeld A.A.,Pius Hospital |
Poppinga D.,Carl von Ossietzky University |
Poppinga D.,Pius Hospital |
And 4 more authors.
Physics in Medicine and Biology | Year: 2014
Optical experiments and theoretical considerations have been undertaken in order to understand the causes of the 'orientation effect' and the 'parabola effect', the artefacts impairing the desired light absorption measurement on radiochromic EBT3 films with flatbed scanners. EBT3 films exposed to doses up to 20.9 Gy were scanned with an Epson Expression 10000XL flatbed scanner in landscape and portrait orientation. The horizontally and vertically polarized light components of the scanner were determined, and another Epson Expression 10000XL flatbed scanner was disassembled to examine its optical components. The optical properties of exposed and unexposed EBT3 films were studied with incident polarized and unpolarized white light, and the transmitted red light was investigated for its polarization and scattering properties including the distribution of the scattering angles. Neutral density filters were studied for comparison. Guidance was sought from the theory of light scattering from rod-like macromolecular structures. The drastic dose-dependent variation of the transmitted total light current as function of the orientation of front and rear polarizers, interpreted by light scattering theory, shows that the radiation-induced polymerization of the monomers of EBT3 films produces light scattering oscillators preferably polarized at right angles with the coating direction of the film. The directional distribution of the scattered light is partly anisotropic, with a preferred scattering plane at right angles with the coating direction, indicating light scattering from stacks of coherently vibrating oscillators piled up along the monomer crystals. The polyester carrier film also participates in these effects. The 'orientation' and 'parabola' artefacts due to flatbed scanning of radiochromic films can be explained by the interaction of the polarization-dependent and anisotropic light scattering from exposed and unexposed EBT3 films with the quantitative difference between the scanner's horizontally and vertically polarized light supply and with the limited directional acceptance of the scanner's light recording system. © 2014 Institute of Physics and Engineering in Medicine.
Albert J.G.,Goethe University Frankfurt |
Wiedbrauck F.,Allgemeines Krankenhaus |
Hollerbach S.,Allgemeines Krankenhaus |
Wienke A.,Martin Luther University of Halle Wittenberg
European Journal of Gastroenterology and Hepatology | Year: 2010
Introduction: Capsule endoscopy (CE) and double-balloon enteroscopy (DBE) detect small bowel bleeding with equal diagnostic yield. We Aimed to detect factors that influence procedural cost of CE and DBE in diagnosing and treating small bowel bleeding, and to compare them with reimbursement. Methods: A cost model analysed procedural cost for diagnostic CE versus diagnostic, unidirectional DBE (scenario 1) and CE plus directed therapeutic DBE (positive findings in CE) versus unidirectional diagnostic plus therapeutic DBE (scenario 2). The frequency of investigations per annum (p.a.) at which cost per procedure is equalized (break-even point) was determined for CE versus DBE. A retrospectively collected cohort of Patients was used to validate the cost model and to compare procedural costs with reimbursement (German diagnosis-related groups, G-DRG). Results: The break-even point at which cost per procedure is equalized for CE versus DBE was reached at 100 procedures p.a. in scenario 1 and 79 in scenario 2 for a rate of therapeutic enteroscopy of 14%, and 27 for a therapeutic enteroscopy rate of 30%. Personnel cost, procedure time, procedures p.a. and the rate of therapeutic enteroscopy had a major influence on procedural cost. In this patient cohort, the 'CE-first' and the 'DBE-first' strategies produced procedural costs of €830 and €1076 per patient to attain a diagnosis, and €1042 versus €1181 to achieve therapeutic enteroscopy, respectively. For this cohort, potential reimbursement was €2320 and €3047 for the 'CE-first' and the 'DBE-first' strategies, respectively (G-DRG). Conclusion: Workflow management of CE versus DBE should consider frequency of investigations p.a. and probability for therapeutic enteroscopy to minimize procedural costs. The cost of DBE increases with less frequent or time-consuming investigations; CE is more robust with regard to these factors. From a third-party payer perspective, a strategy incorporating CE seems to minimize costs in G-DRG. © 2010 Wolters Kluwer Health | Lippincott.
Trabold B.,University of Regensburg |
Lunz D.,University of Regensburg |
Gruber M.,University of Regensburg |
Frohlich D.,Allgemeines Krankenhaus |
Graf B.,University of Regensburg
Injury | Year: 2010
Objective: To evaluate the effect of the inotropes epinephrine, dopamine and dobutamine on expression of endothelial adhesion molecules and on neutrophil adhesion to endothelial cells under dynamic conditions. Methods: Endothelial cells were obtained by collagenase digestion of human umbilical cord veins. Endothelial monolayers were pre-incubated with one of the chosen inotropes, with or without butoxamine, and exposed to interleukin-1. The monolayers were then incubated with fluorescence-labelled anti-human monoclonal antibodies directed against the endothelial adhesion molecules ICAM-1, E-selectin or VCAM-1. Expression of endothelial adhesion molecules was analysed by flow cytometry after pre-incubation of endothelial monolayers with one of the chosen inotropes, with or without butoxamine, and after exposure to interleukin-1. To evaluate the neutrophil adherence, the endothelium was placed on a horizontal shaker-incubator and overlayered with neutrophils. Then, non-adherent neutrophils were removed, and cells were completely dissociated. Finally, neutrophils and endothelial cells were counted by flow cytometry. Results: The expression of E-selectin on endothelium following stimulation with interleukin-1 is attenuated by the inotropes dopamine or dobutamine, but not by epinephrine. The addition of butoxamine does not modify the expression of E-selectin following stimulation with interleukin-1 and pre-incubation with one of the chosen inotropes. The decrease in neutrophil adhesion to endothelium following stimulation with interleukin-1 and addition of inotropes is antagonised by the β-blocker butoxamine. Conclusion: In contrast to the modulation of E-selectin expression on endothelium, the effect of inotropes on neutrophil adhesion to endothelium is regulated by the expression of adhesion molecules on PMNs and mediated by the β-adrenoceptor. © 2010 Elsevier Ltd.
Trabold B.,University of Regensburg |
Lunz D.,University of Regensburg |
Gruber M.,University of Regensburg |
Froehlich D.,Allgemeines Krankenhaus |
Graf B.,University of Regensburg
Surgery | Year: 2010
Background: To evaluate the possible protective effect of sympatholytic medications with respect to neutrophil function, we evaluated the influence of a nonselective β-blocker medication on the interaction of neutrophils and epinephrine after cardiopulmonary bypass. Therefore, we studied the importance of adrenoceptors for the immunomodulation of neutrophils by catecholamines in vitro. Methods: First, we investigated the modulation of neutrophils from healthy volunteers, after stimulation with n-formyl-l-methionyl-l-leucyl-l-phenylalanin (FMLP) in the presence of epinephrine with or without the addition of one of the following adrenergic receptor antagonists: atenolol, butoxamine, pindolol, prazosin, or RS79984. The second part included an investigation of the modulation of neutrophils from patients after operative coronary revascularization with or without extracorporeal circulation after stimulation with FMLP and addition of epinephrine. After loading with anti-CD62l or anti-CD11b antibodies or dihydrorhodamine, the expression of CD62l and CD11b and generation of oxidative free radicals were assessed by flow cytometry. Results: The suppression of oxidative free radical generation, inhibition of CD62l downregulation after stimulation with FMLP, and suppression of CD11b upregulation after FMLP stimulation from epinephrine were all mediated by β2-adrenoceptors. After cardiac surgery with cardiopulmonary bypass, epinephrine inhibited the CD62l downregulation, the suppression of CD11b upregulation, and the generation of oxidative free radicals after FMLP stimulation. The pre-operative administration of β-blockers abolished the immunomodulatory effects of epinephrine on CD62l and CD11b expression and the generation of oxidative free radicals. Conclusion: The immunomodulatory effects of epinephrine on neutrophils remained unchanged irrespective of cardiopulmonary bypass and could contribute to the detrimental effects of epinephrine after heart surgery. The preoperative administration of nonselective β-blockers abolished the immunomodulatory effects of epinephrine in vitro and in patients, and it enhanced the immunocompetence of neutrophils in a context of increased catecholamine levels. © 2010 Mosby, Inc. All rights reserved.
PubMed | Klinikum Braunschweig, Ludwig Maximilians University of Munich, University of Cologne, Evangelisches Krankenhaus and 15 more.
Type: Journal Article | Journal: Leukemia | Year: 2016
We randomized 3375 adults with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome to test whether increasingly intensive chemotherapies assigned at study-entry and analyzed on an intent-to-treat basis improved outcomes. In total, 1529 subjects <60 years were randomized to receive: (1) a first course of induction therapy with high-dose cytarabine and mitoxantrone (HAM) or with standard-dose cytarabine, daunorubicin and 6-thioguanine (TAD) followed by a second course of HAM; (2) granulocyte-colony stimulating factor (G-CSF) or no G-CSF before induction and consolidation courses; and (3) high-dose therapy and an autotransplant or maintenance chemotherapy. In total, 1846 subjects 60 years were randomized to receive: (1) a first induction course of HAM or TAD and second induction course of HAM (if they had bone marrow blasts 5% after the first course); and (2) G-CSF or no G-CSF as above. Median follow-up was 7.4 years (range, 1 day to 14.7 years). Five-year event-free survivals (EFSs) for subjects receiving a first induction course of HAM vs TAD were 17% (95% confidence interval, 15, 18%) vs 16% (95% confidence interval 14, 18%; P=0.719). Five-year EFSs for subjects randomized to receive or not receive G-CSF were 19% (95% confidence interval 16, 21%) vs 16% (95% confidence interval 14, 19%; P=0.266). Five-year relapse-free survivals (RFSs) for subjects <60 years receiving an autotransplant vs maintenance therapy were 43% (95% confidence interval 40, 47%) vs 40 (95% confidence interval 35, 44%; P=0.535). Many subjects never achieved pre-specified landmarks and consequently did not receive their assigned therapies. These data indicate the limited impact of more intensive therapies on outcomes of adults with AML. Moreover, none of the more intensive therapies we tested improved 5-year EFS, RFS or any other outcomes.
PubMed | Evangelismos Hospital, ACO, Allgemeines Krankenhaus, IRCCS and 3 more.
Type: Clinical Trial | Journal: The Annals of thoracic surgery | Year: 2014
In blunt thoracic aortic injury, thoracic endovascular aortic repair (TEVAR) offers a less invasive alternative to open chest surgery. New reliable and accurate stent grafts have widened the endovascular treatment options. We report our experience with the Relay stent graft Bolton Medical, Sunrise, FL; Barcelona, Spain) for treatment of this injury.Relay Endovascular Registry for Thoracic Disease (RESTORE) is a multicenter, prospective European registry, which enrolled patients treated with the Relay stent graft for thoracic aortic diseases from April 2005 to January 2009. Regular follow-up examinations were conducted for up to 24 months. This paper analyzes the cohort of patients treated for traumatic aortic injury.Forty adult trauma patients from 12 European centers underwent TEVAR. Mean age was 40 years and 34 patients were male. The proximal landing zone involved aortic arch zones 1 to 2 in 40% and zone 3 in 55% of procedures. Technical success was achieved in all cases. One (2.5%) patient suffered a rupture of the iliac artery. No patient developed procedure-related paraplegia or required conversion to open surgery. Follow-up imaging demonstrated complete exclusion of the traumatic tear and regression of the false aneurysms without endoleak or graft infolding. One late device-related complication was reported; penetration of the distal end of the stent graft treated by stent-graft extension. Thirty-day mortality was 2.5 % (n = 1), and late mortality 2.5% due to a secondary accident. Actuarial 2-year survival was 93.7%.Thoracic endovascular aortic repair with the Relay stent graft is a safe and effective treatment for patients with traumatic aortic injury.
Zipfel B.,Deutsches Herzzentrum Berlin |
Coppi G.,Nuovo Ospedale SantAgostino Estense |
Czerny M.,Allgemeines Krankenhaus |
Tealdi D.G.,IRCCS Policlinico San Donato Milanese |
And 5 more authors.
Journal of Vascular Surgery | Year: 2011
Purpose: Thoracic endovascular aortic repair is increasingly becoming the standard treatment of many thoracic aortic pathologies. New reliable and accurate stent grafts are emerging to widen the endovascular treatment options. We report the results of RELAY (Bolton Medical, Barcelona, Spain) in the large RELAY Endovascular Registry for Thoracic Disease (RESTORE) European registry. Methods: RESTORE is a multicenter, prospective European registry involving 22 centers in seven European countries. The RELAY device is composed of a stent graft (self-expanding nitinol stents and a polyester vascular graft) and a delivery device specifically designed for the thoracic aorta. Included were acute and elective patients presenting with a variety of pathologies (aneurysms, dissections, ulcerations, intramural hematomas, pseudoaneurysms) and lesions in different aortic and anatomic locations (ascending, arch, descending and thoracoabdominal). Results: The registry enrolled 304 patients from April 2005 to January 2009. All-cause mortality at 30 days was 7.2%. Freedom from all cause mortality and freedom from device- and procedure-related mortality at 2 years were 78.5% and 95.9%, respectively. An average of 1.26 graft components were used per patient, with a technical success of 97.7% irrespective of the etiology. Early endoleak rate was 4.6%. Perioperatively, stroke and paraplegia were registered in 1.6% and 2.0%, respectively. Conclusions: The results of RESTORE support the safety of thoracic endovascular aortic repair with the RELAY stent graft, even in acute and complicated situations. The device was highly efficient in angulated aortic anatomies, with acceptable mortality and a low rate of neurologic complications. © 2011 Society for Vascular Surgery.