34 results on '"Mitzner SR"'
Search Results
2. Extracorporeal liver support by recirculating albumin dialysis: analysing the effect of the first clinically used generation of the MARSystem
- Author
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Klammt, S, primary, Stange, J, additional, Mitzner, SR, additional, Peszynski, P, additional, Peters, E, additional, Liebe, S., additional, Klammt, S, additional, Mitzner, S. R., additional, and Liebe, S, additional
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- 2002
- Full Text
- View/download PDF
3. IMPACT OF ALBUMIN-TRIGGERED DIALYSIS ON THE CLINICAL OUTCOME IN HEPATORENAL SYNDROME
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Stange, J., primary and Mitzner, SR., additional
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- 1996
- Full Text
- View/download PDF
4. Cost-effectiveness of the artificial liver support system MARS in patients with acute-on-chronic liver failure.
- Author
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Hessel FP, Bramlage P, Wasem J, and Mitzner SR
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- 2010
- Full Text
- View/download PDF
5. Extracorporeal cell therapy with granulocytes in a pig model of Gram-positive sepsis.
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Sauer M, Altrichter J, Kreutzer HJ, Lögters T, Scholz M, Nöldge-Schomburg G, Schmidt R, and Mitzner SR
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- 2009
- Full Text
- View/download PDF
6. Extracorporeal support of the failing liver.
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Mitzner SR, Stange J, Peszynski P, Klammt S, Mitzner, Steffen R, Stange, Jan, Peszynski, Piotr, and Klammt, Sebastian
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- 2002
- Full Text
- View/download PDF
7. Drain the brain: albumin dialysis for intracranial hypertension.
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Mitzner SR and Mitzner, Steffen R
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- 2006
- Full Text
- View/download PDF
8. Effects of Bioreactor-Oxygenation During Extracorporeal Granulocytes Treatment in Septic Patients.
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Sauer M, Richter G, Altrichter J, Wild T, Doß F, Mencke T, Ehler J, Doß S, Koch S, Schubert A, Nöldge-Schomburg G, and Mitzner SR
- Subjects
- Adult, Aged, Blood Gas Analysis, Cytokines metabolism, Glucose metabolism, Hospital Mortality, Humans, Lactates metabolism, Male, Middle Aged, Oxygen metabolism, Prospective Studies, Reactive Oxygen Species metabolism, Sepsis immunology, Sepsis physiopathology, Bioreactors, Extracorporeal Circulation methods, Granulocytes metabolism, Sepsis therapy
- Abstract
A granulocyte bioreactor for the extracorporeal treatment was developed to enhance the immune cell function in patients with severe sepsis. The influence of oxygenation on the used cells was tested in a prospective clinical study. Ten patients with severe sepsis were treated twice with the granulocyte bioreactor. The used cells were screened for functionality; values of blood gases, glucose and lactate were obtained from the recirculating bioreactor circuit. Five patients were treated with an oxygenator setup (Oxy group), five without oxygenator (Non-Oxy group). The overall in-hospital mortality was 50%. Significantly lower values of oxygen saturation, partial oxygen pressure, lactate, oxyburst and phagocytosis were seen in the Non-Oxy group compared with the Oxy group in the bioreactor circuit. Further studies with this approach are encouraged and should focus on the influence of oxygenation on production of reactive oxygen species and cytokines of used cells., (© 2018 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)
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- 2018
- Full Text
- View/download PDF
9. Immunoadsorption as a Long-Term Therapy in Recurrent Focal Segmental Glomerulosclerosis After Renal Transplantation.
- Author
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Frimmel S, Mitzner SR, and Koball S
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- Female, Humans, Long-Term Care, Middle Aged, Recurrence, Time, Treatment Outcome, Glomerulosclerosis, Focal Segmental therapy, Immunosorbent Techniques, Kidney Transplantation, Postoperative Complications therapy
- Published
- 2017
- Full Text
- View/download PDF
10. Bioartificial Therapy of Sepsis: Changes of Norepinephrine-Dosage in Patients and Influence on Dynamic and Cell Based Liver Tests during Extracorporeal Treatments.
- Author
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Sauer M, Altrichter J, Haubner C, Pertschy A, Wild T, Doß F, Mencke T, Thomsen M, Ehler J, Henschel J, Doß S, Koch S, Richter G, Nöldge-Schomburg G, and Mitzner SR
- Subjects
- Adult, Aged, Aged, 80 and over, Biomarkers metabolism, Cell Count, Cohort Studies, Cytochrome P-450 CYP1A2, Cytokines metabolism, Dose-Response Relationship, Drug, Hemodynamics, Hep G2 Cells, Humans, Inflammation pathology, L-Lactate Dehydrogenase metabolism, Liver Function Tests, Male, Middle Aged, Norepinephrine administration & dosage, Survival Analysis, Treatment Outcome, Extracorporeal Circulation methods, Liver pathology, Liver, Artificial, Norepinephrine therapeutic use, Sepsis pathology, Sepsis therapy
- Abstract
Purpose. Granulocyte transfusions have been used to treat immune cell dysfunction in sepsis. A granulocyte bioreactor for the extracorporeal treatment of sepsis was tested in a prospective clinical study focusing on the dosage of norepinephrine in patients and influence on dynamic and cell based liver tests during extracorporeal therapies. Methods and Patients. Ten patients with severe sepsis were treated twice within 72 h with the system containing granulocytes from healthy donors. Survival, physiologic parameters, extended hemodynamic measurement, and the indocyanine green plasma disappearance rate (PDR) were monitored. Plasma of patients before and after extracorporeal treatments were tested with a cell based biosensor for analysis of hepatotoxicity. Results. The observed mortality rate was 50% during stay in hospital. During the treatments, the norepinephrine-dosage could be significantly reduced while mean arterial pressure was stable. In the cell based analysis of hepatotoxicity, the viability and function of sensor-cells increased significantly during extracorporeal treatment in all patients and the PDR-values increased significantly between day 1 and day 7 only in survivors. Conclusion. The extracorporeal treatment with donor granulocytes showed promising effects on dosage of norepinephrine in patients, liver cell function, and viability in a cell based biosensor. Further studies with this approach are encouraged.
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- 2016
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11. First description of single-pass albumin dialysis combined with cytokine adsorption in fulminant liver failure and hemophagocytic syndrome resulting from generalized herpes simplex virus 1 infection.
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Frimmel S, Schipper J, Henschel J, Yu TT, Mitzner SR, and Koball S
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- Adsorption, Biopsy, Critical Care, Female, Hepatitis surgery, Hepatitis therapy, Herpesvirus 1, Human, Humans, Immunosuppression Therapy, Inflammation, Liver pathology, Liver Failure, Acute complications, Liver Transplantation, Middle Aged, Albumins chemistry, Cytokines metabolism, Herpes Simplex complications, Liver Failure, Acute surgery, Lymphohistiocytosis, Hemophagocytic therapy, Renal Dialysis methods
- Published
- 2014
- Full Text
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12. No sustained impact of intermittent extracorporeal liver support on thrombocyte time course in a randomized controlled albumin dialysis trial.
- Author
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Klammt S, Mitzner SR, Reisinger EC, and Stange J
- Subjects
- Humans, Platelet Count, Time Factors, Blood Platelets metabolism, Liver Failure therapy, Renal Dialysis methods, Serum Albumin metabolism
- Abstract
Reduction of platelets is a common finding in patients with liver disease and can be aggravated by extracorporeal therapies, e.g. artificial liver support. The impact of extracorporeal albumin dialysis on the time count and time course of platelets in liver failure patients was evaluated in a randomized controlled clinical trial. Mean thrombocyte reduction during a single extracorporeal liver support therapy was -15.1% [95%CI: -17.7; -12.5]. No differences were found between treatments of patients with a more reduced platelet count (<100 GPT/L: -15.6% [-19.5; -11.7%]; n = 43) compared to patients with normal or slightly decreased thrombocytes (-14.6% [-18.3%; -11.0%]; n = 43; P = 0.719). The variation of platelet count within 24 h after onset of extracorporeal therapy treatment was less, albeit significant (-3.5% [-6.3%; -0.7%], P < 0.016). Absolute thrombocyte variability was comparable between both groups (with extracorporeal therapy -5.6 GPT/L [-9.7; -1.4], without extracorporeal therapy -1.3 GPT/L [-7.3; 4.7]; P = 0.243), whereas relative decrease of thrombocytes within a 24-h period of extracorporeal therapy was greater than the changes in patients without extracorporeal therapy (-3.5% [-6.3%; -0.7%] vs. 2.0% [-2.0%; 5.9%]; P = 0.026]. Within a period of two weeks after enrollment, no significant differences of platelet count were observed either between the two groups or in the time course (P(group) = 0.337, P(time) = 0.277). Reduction of platelets during intermittent extracorporeal liver support was less pronounced within a 24-h period as before and after a single treatment and was comparable to variations in the control group without extracorporeal therapy., (© 2014 The Authors. Therapeutic Apheresis and Dialysis © 2014 International Society for Apheresis.)
- Published
- 2014
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13. Role of different replacement fluids during extracorporeal treatment in a pig model of sepsis.
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Sauer M, Altrichter J, Mencke T, Klöhr S, Thomsen M, Kreutzer HJ, Nöldge-Schomburg G, and Mitzner SR
- Subjects
- Animals, Disease Models, Animal, Female, Hydroxyethyl Starch Derivatives administration & dosage, Plasma Substitutes administration & dosage, Sepsis microbiology, Staphylococcal Infections microbiology, Staphylococcus aureus isolation & purification, Survival Rate, Swine, Extracorporeal Circulation methods, Fluid Therapy methods, Sepsis therapy, Staphylococcal Infections therapy
- Abstract
In an extracorporeal combination therapy, the impact of different replacement fluids on survival was tested in a bacterial sepsis model in pigs. In an animal study 19 pigs, weighing 7.5-11.1 kg, were included. All groups received an intravenous lethal dose of live Staphylococcus aureus over 1 h. The animals were treated by an extracorporeal circuit consisting of online centrifugation and subsequent plasma filtration for 4 h. The extracorporeal circuit was pre-filled with 400 mL replacement fluid. In the P0 group 100% hydroxyethyl starch 130/0.4 was used as replacement fluid; in the P30 group 30% pig plasma and 70% hydroxyethyl starch; and in the P100 group 100% pig plasma. The observation time was 7 days. All animals of the group P100 survived, while all animals of group P0 and five out of seven animals of the P30 group died during the observation time. Extracorporeal therapy consisting of online centrifugation and plasma filtration with 100% pig plasma as replacement fluid significantly improved survival in a pig model of sepsis. Further studies with this approach are encouraged., (© 2012 The Authors. Therapeutic Apheresis and Dialysis © 2012 International Society for Apheresis.)
- Published
- 2013
- Full Text
- View/download PDF
14. Improvement of hemodynamic and inflammatory parameters by combined hemoadsorption and hemodiafiltration in septic shock: a case report.
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Mitzner SR, Gloger M, Henschel J, and Koball S
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- Adsorption, Aged, 80 and over, Humans, Inflammation blood, Inflammation pathology, Inflammation physiopathology, Male, Time Factors, Hemodiafiltration, Hemodynamics, Shock, Septic blood, Shock, Septic physiopathology, Shock, Septic therapy
- Published
- 2013
- Full Text
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15. Plasma separation by centrifugation and subsequent plasma filtration: impact on survival in a pig model of sepsis.
- Author
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Sauer M, Altrichter J, Mencke T, Klöhr S, Thomsen M, Kreutzer HJ, Nöldge-Schomburg G, and Mitzner SR
- Subjects
- Animals, Biomarkers analysis, Centrifugation, Cytokines analysis, Disease Models, Animal, Extracorporeal Circulation, Female, Filtration methods, Kidney Function Tests, Liver Function Tests, Plasmapheresis methods, Prospective Studies, Sepsis microbiology, Staphylococcal Infections microbiology, Statistics, Nonparametric, Swine, Sepsis blood, Sepsis therapy, Staphylococcal Infections blood, Staphylococcal Infections therapy
- Abstract
The impact on survival of a combination of plasma separation by centrifugation and subsequent plasma filtration was tested in a bacterial sepsis model in pigs. In this animal study 19 pigs were included. Groups II and III received an intravenous lethal dose of live Staphylococcus aureus over 1 h; group I received saline (non-septic control--NC). Groups I and II were treated by an extracorporeal circuit consisting of online centrifugation and subsequent plasma filtration (group II: treated group--TG) for 4 h; group III had no specific treatment (septic control, SC). The observation time was 7 days. All animals of group I (NC) and group II (TG) survived, while all animals of group III (SC) died during the observation time. Extracorporeal therapy with online centrifugation and plasma filtration significantly improved survival in a pig model of sepsis. Further studies with this approach are encouraged., (© 2012 The Authors. Therapeutic Apheresis and Dialysis © 2012 International Society for Apheresis.)
- Published
- 2012
- Full Text
- View/download PDF
16. Extracorporeal liver support-albumin dialysis with the Molecular Adsorbent Recirculating System (MARS).
- Author
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Mitzner SR
- Subjects
- Hepatic Encephalopathy etiology, Hepatic Encephalopathy therapy, Humans, Hyperbilirubinemia etiology, Hyperbilirubinemia therapy, Liver Failure complications, Treatment Outcome, Albumins therapeutic use, Liver Failure therapy, Renal Dialysis instrumentation, Renal Dialysis methods
- Abstract
Extracorporeal liver support has been a much studied topic throughout the last 50 years. Albumin dialysis as a therapeutic option for patients with acute liver failure or acute decompensation of chronic liver disease was introduced in the mid-nineties. The Molecular Adsorbent Recirculating System (MARS) is based on the concept of albumin dialysis and allows for the removal of protein-bound as well as water-soluble toxins. Besides its role as a sufficient volume expander human serum albumin is an important scavenger for molecules with pathophysiological relevance in liver failure. Albumin dialysis enables the selective regeneration of patient's albumin resulting in an increase of albumin binding capacity. Clinically, an improvement of central and local hemodynamics as well as liver-, brain-, and kidney-functions were observed. Thus, the treatment can contribute to liver regeneration and stabilization of vital organ functions and thus help to bridge patients to liver transplantation or to recovery of native liver function. Proper patient selection is critical for clinical success. Aggressive treatment of infections and sepsis seems to be a decisive pre-requisite for its safe and efficient use. Cautious anticoagulation with heparin is the common standard. Citrate use is recommended for patients prone to bleeding. Today, albumin dialysis MARS is among the best studied liver support methods. It appears as a valuable therapeutic tool for the treatment of various complications of of liver failure, especially hemodynamic instability and hepatic encephalopathy. Further studies will need to help defining the optimal patient selection and technical process parameters such as session length and frequency of treatment.
- Published
- 2011
17. Extracorporeal cell therapy of septic shock patients with donor granulocytes: a pilot study.
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Altrichter J, Sauer M, Kaftan K, Birken T, Gloger D, Gloger M, Henschel J, Hickstein H, Klar E, Koball S, Pertschy A, Nöldge-Schomburg G, Vagts DA, and Mitzner SR
- Subjects
- Aged, Female, Follow-Up Studies, Humans, Male, Middle Aged, Pilot Projects, Prospective Studies, Treatment Outcome, Critical Care methods, Granulocytes transplantation, Shock, Septic therapy
- Abstract
Introduction: Neutrophil granulocytes are the first defense line in bacterial infections. However, granulocytes are also responsible for severe local tissue impairment. In order to use donor granulocytes, but at the same time to avoid local side effects, we developed an extracorporeal immune support system. This first-in-man study investigated whether an extracorporeal plasma treatment with a granulocyte bioreactor is tolerable in patients with septic shock. A further intention was to find suitable efficacy end-points for subsequent controlled trials., Methods: The trial was conducted as a prospective uncontrolled clinical phase I/II study with 28-day follow-up at three university hospital intensive care units. Ten consecutive patients (five men, five women, mean age 60.3 ± 13.9 standard deviation (SD) years) with septic shock with mean ICU entrance scores of Acute Physiology and Chronic Health Evaluation (APACHE) II of 29.9 ± 7.2 and of Simplified Acute Physiology Score (SAPS) II of 66.2 ± 19.5 were treated twice within 72 hours for a mean of 342 ± 64 minutes/treatment with an extracorporeal bioreactor containing 1.41 ± 0.43 × 10E10 granulocytes from healthy donors. On average, 9.8 ± 2.3 liters separated plasma were treated by the therapeutic donor cells. Patients were followed up for 28 days., Results: Tolerance and technical safety during treatment, single organ functions pre/post treatment, and hospital survival were monitored. The extracorporeal treatments were well tolerated. During the treatments, the bacterial endotoxin concentration showed significant reduction. Furthermore, noradrenaline dosage could be significantly reduced while mean arterial pressure was stable. Also, C-reactive protein, procalcitonin, and human leukocyte antigen DR (HLA-DR) showed significant improvement. Four patients died in the hospital on days 6, 9, 18 and 40. Six patients could be discharged., Conclusions: The extracorporeal treatment with donor granulocytes appeared to be well tolerated and showed promising efficacy results, encouraging further studies., Trial Registration: ClinicalTrials.gov Identifier: NCT00818597.
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- 2011
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18. Neutrophil-derived circulating free DNA (cf-DNA/NETs), a potential prognostic marker for mortality in patients with severe burn injury.
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Altrichter J, Zedler S, Kraft R, Faist E, Mitzner SR, Sauer M, Windolf J, Scholz M, and Lögters T
- Abstract
The predictive value of circulating free DNA/neutrophil extracellular traps (cf-DNA/NETs) has recently been shown in patients with major trauma for sepsis, multiple organ failure, and mortality. Here we report on the predictive potential of cf-DNA/NETs for mortality in patients with severe burn injury. In a prospective study 32 patients with severe burn injury were included. Blood samples were sequentially obtained on day 1, 3, 5, and 7 after admission. cf-DNA/NETs was directly quantified from plasma by means of rapid fluorescence assay. Time kinetics of cf-DNA/NETs were correlated with clinical data, C-reactive protein (CRP), procalcitonin (PCT), and interleukin (IL)-6. Furthermore sensitivity, specificity, and positive and negative predictive value, as well as receiver operation characteristic (ROC) curves were calculated. Seven patients died within the first month after burn injury. cf-DNA/NETs values from these patients were significantly increased already on day 1 and 3 after admission compared with patients who survived (p < 0.01). In contrast, PCT levels of nonsurvivors were significantly elevated on day 3 and 5 (p < 0.01), while CRP and IL-6 did not show any significant difference between survivors and nonsurvivors. At a cutoff of 255 ng/ml, cf-DNA/NETs had sensitivity of 0.8 and specificity of 0.74. ROC revealed largest areas under the curve (AUC) for cf-DNA/NETs on day 1 (0.851) and 3 (0.883) after admission. For all values between day 1 and 7, AUC was 0.815. cf-DNA/NETs seems to be a rapid, valuable marker for prediction of mortality in burn patients. A larger confirmation trial ought to be carried out.
- Published
- 2010
- Full Text
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19. Use of preconditioned human phagocytes for extracorporeal adsorption of viruses.
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Oberender F, Oberender H, Altrichter J, Reisinger EC, and Mitzner SR
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- Cell Line, Humans, Viral Load, Disinfection methods, Enterovirus physiology, Hepatitis B virus physiology, Phagocytes virology, Virology methods, Virus Attachment
- Abstract
Conventional treatment of severe viral disease is limited by the narrow choice as well as the often-significant side effects or lack of clear efficacy of antiviral chemotherapy. At the same time, however, it is known that a reduction in viral load leads to significant clinical improvement in a number of important viral diseases. In this paper we discuss the possibility of using preconditioned human phagocytes in an extracorporeal biohybrid system for adsorption of viral pathogens. We present data from in vitro experiments testing adsorption of an enterovirus and of hepatitis B virus (HBV) by a preconditioned human promyelocytic cell line. While no clearance of HBV could be detected, the results revealed a near elimination of enterovirus with the cell line displaying robust viability. Enterovirus titers of 1000 (reciprocal) were reduced to a mean titer of 10(0.6) CCID(50) with no virus detectable after adsorption in two out of five samples. Titers of 10000 (reciprocal) were in turn reduced to a mean of 10(1.4) CCID(50). The kinetics of the process was remarkable with this near elimination of the pathogen occurring within only 15min. Extracorporeal viral adsorption by a cellular biohybrid system appears feasible. Pairing target pathogens with suitable cell lines may offer a versatile antiviral technology., (Copyright 2010 Elsevier B.V. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
20. Liver support 2009: time for another revolution?
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Mitzner SR and Kaplan AA
- Subjects
- Albumins administration & dosage, Humans, Liver Failure etiology, Liver Failure mortality, Dialysis methods, Liver Failure therapy, Liver Transplantation methods
- Published
- 2009
- Full Text
- View/download PDF
21. Safety evaluation for a cell-based immune support system in an ex vivo rat model of gram-negative sepsis.
- Author
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Sauer M, Altrichter J, Kreutzer HJ, Schmidt H, Nöldge-Schomburg G, Schmidt R, and Mitzner SR
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- Animals, Disease Models, Animal, Escherichia coli Infections immunology, Escherichia coli Infections therapy, Gram-Negative Bacterial Infections immunology, Granulocytes immunology, HL-60 Cells, Hemodynamics, Humans, Male, Rats, Rats, Inbred Strains, Sepsis immunology, Sepsis microbiology, Survival Rate, Gram-Negative Bacterial Infections therapy, Granulocytes transplantation, Sepsis therapy
- Abstract
Granulocyte dysfunction is a central component of immunodeficiency in septic patients. Granulocyte transfusions appear to be pathophysiologically useful; however, they cause unwanted side-effects in the lungs and other organs. This study evaluates the safety of an extracorporeal immune support system with granulocytic cells in a rat model of Gram-negative sepsis. Three groups of male CD rats received either saline (control group, I), a dose of Escherichia coli O7:K1 lethal to 90% of the animals (LD90) (septic group, II), or an LD90 dose of E. coli that was incubated with the human promyelocytic leukemia cell line (HL-60) (differentiated into the granulocytic direction) for 20 min prior to infusion (second septic group, III). The animals were observed for seven days. Pre-treatment with HL-60 cells resulted in no adverse effects in the group III animals. Significantly lower bacterial counts and endotoxin levels in the plasma were detected after 24 h as compared to group II (P < 0.05). Group III animals had better weight gain and more stable hemodynamics than group II animals (P < 0.01). Seven day survival was 0/8 in group II, 6/8 in group III, and 8/9 in group I (log-rank test: II-III: P < 0.001). The data suggest that extracorporeal use of granulocytes allows the therapeutic use of these cells while avoiding unwanted effects resulting from direct contact to internal organs.
- Published
- 2009
- Full Text
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22. Albumin dialysis MARS: knowledge from 10 years of clinical investigation.
- Author
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Mitzner SR, Stange J, Klammt S, Koball S, Hickstein H, and Reisinger EC
- Subjects
- Animals, Clinical Trials as Topic, Humans, Membranes, Artificial, Albumins therapeutic use, Dialysis methods, Liver Failure therapy
- Abstract
A decade ago, albumin dialysis was introduced as a new extracorporeal detoxification method for patients with liver failure. Today, the molecular adsorbent recirculating system is the most frequently used type of albumin dialysis and most studied liver-support technique. Numerous preclinical and clinical studies demonstrated the importance of albumin as a scavenger for molecules with pathophysiological relevance in liver failure. Albumin dialysis enables the selective regeneration of albumin. The resulting increase of albumin binding capacity is paralleled by improvement of central and local hemodynamics and liver, brain, and kidney functions. The treatment can contribute to liver regeneration and prolongation of patient survival in the context of acute liver failure, decompensated chronic liver disease, and bridging of patients to liver transplantation. Proper patient selection is critical for clinical success. Aggressive treatment of infections and sepsis seems to be a decisive prerequisite for its safe and efficient use. Cautious anticoagulation with heparin is the common standard. Citrate use is recommended for patients prone to bleeding. Taken together, albumin dialysis represents a valuable therapeutic tool for the treatment of various types of liver failure. Ongoing and future studies will help define the optimal patient selection and technical process parameters such as session length and frequency of treatment.
- Published
- 2009
- Full Text
- View/download PDF
23. Improvement of impaired albumin binding capacity in acute-on-chronic liver failure by albumin dialysis.
- Author
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Klammt S, Mitzner SR, Stange J, Loock J, Heemann U, Emmrich J, Reisinger EC, and Schmidt R
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- Adult, Albumins chemistry, Benzodiazepines chemistry, Bile Acids and Salts chemistry, Bilirubin chemistry, Binding Sites, Dansyl Compounds chemistry, Female, Fibrosis metabolism, Humans, Liver Failure therapy, Male, Middle Aged, Sarcosine analogs & derivatives, Sarcosine chemistry, Treatment Outcome, Albumins metabolism, Dialysis methods
- Abstract
Extracorporeal albumin dialysis (ECAD) enables the elimination of albumin bound substances and is used as artificial liver support system. Albumin binding function for the benzodiazepine binding site specific marker Dansylsarcosine was estimated in plasma samples of 22 patients with cirrhosis and hyperbilirubinaemia (ECAD: n = 12; control: n = 10) during a period of 30 days in a randomized controlled clinical ECAD trial. Albumin Binding Capacity (ABiC) at baseline was reduced to 31.8% (median; range 24%-74%) and correlated to the severity of liver disease. Within two weeks a significant improvement of ABiC and a reduction of the albumin bound markers bilirubin and bile acids were observed in the ECAD group. During single treatments a significant decrease of albumin bound substances (bilirubin and bile acids) as well as an increase in ABiC was observed. In the control group, baseline ABiC was significantly lower in patients who died during study period (34.2% vs. 41.7%; P < 0.028), whereas no significant differences were observed for CHILD, coagulation factors, albumin, bile acids nor bilirubin. At baseline 13 patients had a severely impaired ABiC (<40%), improvement of ABiC was more frequent in the ECAD group (5/6) than in the SMT group (2/7). Reduced albumin binding function is present in decompensated liver failure and is related to severity and 30 day survival. ABiC can be improved by ECAD. The beneficial effect of this treatment may be related to the improvement of albumin binding function more than to the elimination of specific substances. Characterization of albumin function by the ABiC test may help to evaluate different liver support systems and other therapeutic measures.
- Published
- 2008
- Full Text
- View/download PDF
24. Albumin dialysis: an update.
- Author
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Mitzner SR
- Subjects
- Humans, Liver Regeneration, Treatment Outcome, Albumins therapeutic use, Liver Failure therapy, Renal Dialysis methods
- Abstract
Purpose of Review: To review the current literature about albumin dialysis-based liver support., Recent Findings: The literature suggests that the molecular adsorbent recirculating system of albumin dialysis is a useful tool to treat acute liver failure, decompensated chronic liver disease, and to provide a bridge for patients to liver transplantation. The reported clinical benefits include an improvement in central and local haemodynamics as well as organ functions (liver, brain, kidney). The treatment can contribute to liver regeneration and prolongation of patient survival. Proper patient selection is critical for clinical success., Summary: Albumin regeneration has developed into a central component of modern liver support technologies. Albumin dialysis using the molecular adsorbent recirculating system is the most frequently used and best studied liver support technique at present time. Ongoing and future clinical studies will help define the place of albumin dialysis in liver failure therapy.
- Published
- 2007
- Full Text
- View/download PDF
25. Economic evaluation and 1-year survival analysis of MARS in patients with alcoholic liver disease.
- Author
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Hessel FP, Mitzner SR, Rief J, Guellstorff B, Steiner S, and Wasem J
- Subjects
- Adult, Case-Control Studies, Cost-Benefit Analysis, Evaluation Studies as Topic, Female, Follow-Up Studies, Health Expenditures statistics & numerical data, Humans, Liver Diseases, Alcoholic therapy, Male, Middle Aged, Quality-Adjusted Life Years, Renal Dialysis mortality, Retrospective Studies, Sorption Detoxification mortality, Survival Analysis, Hospital Costs statistics & numerical data, Liver Diseases, Alcoholic economics, Liver Diseases, Alcoholic mortality, Renal Dialysis economics, Sorption Detoxification economics
- Abstract
Objective of this study was to determine 1-year survival, costs and cost-effectiveness of the artificial liver support system Molecular Adsorbent Recirculating System (MARS) in patients with acute-on-chronic liver failure (ACLF) and an underlying alcoholic liver disease. In a case-control study, 13 patients treated with MARS were compared to 23 controls of similar age, sex and severity of disease. Inpatient hospital costs data were extracted from patients' files and hospital's internal costing. Patients and treating GPs were contacted, thus determining resource use and survival 1-year after treatment. Mean 1-year survival time in MARS group was 261 days and 148 days in controls. Kaplan-Meier analysis shows advantages of MARS patients (Logrank: P=0.057). Direct medical costs per patient for initial hospital stay and 1-year follow-up from a payer's perspective were Euro 18,792 for MARS patients and Euro 9638 for controls. The costs per life-year gained are Euro 29,719 (time horizon 1 year). From a societal perspective, the numbers are higher (costs per life-year gained: Euro 79,075), mainly because of the fact that there is no regular reimbursement of MARS and therefore intervention costs were not calculated from payer's perspective. A trade-off between medical benefit and higher costs has to be made, but 1-year results suggest an acceptable cost-effectiveness of MARS. Prolonging the time horizon and including indirect costs, which will be done in future research, would probably improve cost-effectiveness.
- Published
- 2003
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26. The molecular adsorbents recycling system as a liver support system based on albumin dialysis: a summary of preclinical investigations, prospective, randomized, controlled clinical trial, and clinical experience from 19 centers.
- Author
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Stange J, Hassanein TI, Mehta R, Mitzner SR, and Bartlett RH
- Subjects
- Adsorption, Albumins, Controlled Clinical Trials as Topic, Dialysis, Humans, Liver Transplantation, Multicenter Studies as Topic, Prospective Studies, Randomized Controlled Trials as Topic, Liver Failure therapy, Liver, Artificial, Membranes, Artificial, Sorption Detoxification
- Abstract
Artificial liver support aims to prolong survival time of patients with liver failure by detoxification. Albumin as a molecular adsorbent in dialysis solution is capable of attracting even tightly albumin-bound toxins from blood into the dialysate if a specific dialysis membrane is used and if the albumin's binding sites are on-line-purified by a sorbent/dialysis-based recycling system (i.e., molecular adsorbents recycling system, or MARS). The MARS technology has been shown to remove water-soluble and albumin-bound toxins and to provide renal support in case of renal failure. Fourteen centers have reported that MARS treatment improved mental status of patients with liver failure and hepatic encephalopathy. In treating liver failure and cholestasis, MARS was associated with hemodynamic stabilization, improvement of hepatic and kidney function, and disappearance of pruritus. In hepatic failure and hepatorenal syndrome, a prospective, randomized, controlled trial of MARS treatment was able to prolong survival time significantly. MARS has been used in 26 patients with acute liver failure or primary graft dysfunction. Nineteen centers reporting on 103 patients have shown that MARS treatment is safe, easy to handle, feasible, and effective.
- Published
- 2002
- Full Text
- View/download PDF
27. Economic evaluation of MARS--preliminary results on survival and quality of life.
- Author
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Hessel FP, Mitzner SR, Rief J, Gress S, Guellstorff B, and Wasem J
- Subjects
- Adult, Cost-Benefit Analysis, Female, Humans, Male, Middle Aged, Quality of Life, Quality-Adjusted Life Years, Renal Dialysis economics, Retrospective Studies, Sorption Detoxification economics, Survival Analysis, Liver Failure, Acute economics, Liver Failure, Acute mortality, Liver Failure, Acute therapy, Renal Dialysis mortality, Sorption Detoxification mortality
- Abstract
Objectives: The short-term medical benefit of the liver dialysis system MARS in patients with severe acute liver disease has clearly been demonstrated. An economic analysis of MARS has not been presented previously. Objective of the study is to calculate the costs per life saved and life year gained and to measure health related quality of life in patients who survived acute liver failure. First results on survival and HRQL are presented here., Study Design: Cost effectiveness and cost utility analysis of MARS are performed. All patients since 1993 with chronic liver failure (Bilirubin > 300 micro mol/l) of the university hospital Rostock are included in the original sample (n = 141). Survival data are calculated. Surviving patients were contacted personally, thus quality of life data (EQ 5D and SF12) determined. Patients were compared in case control study design. In a later stage inpatient hospital costs, direct and indirect outpatients costs are included in the analysis., Preliminary Results: MARS-Patients show a higher survival: Kaplan-Meier cumulative survival after 100 days: 0.59 after MARS, 0.39 without (P <0.05). There was no significant difference in health related quality of life (SF12 and EQ-D). Calculations of quality adjusted life years (QALYs) result in 0.116 QALYs gained by treatment of one patient with MARS in one year., Discussion: First preliminary results suggest that 1 year after therapy MARS seems to have a positive effect concerning survival rate, survival time and QALYs gained. Final results of cost-effectiveness and cost-utility analysis will soon be presented.
- Published
- 2002
- Full Text
- View/download PDF
28. Albumin dialysis using the molecular adsorbent recirculating system.
- Author
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Mitzner SR, Stange J, Klammt S, Peszynski P, and Schmidt R
- Subjects
- Adsorption, Cost-Benefit Analysis, Humans, Renal Dialysis economics, Renal Dialysis mortality, Survival Rate, Albumins administration & dosage, Renal Dialysis methods
- Abstract
Liver support systems based on either dialysis, filtration, and adsorption or plasmaperfusion over hepatocytes have been tested clinically with varying success. A new approach in this field is the selective removal of albumin-bound end products of metabolism. This can be achieved in a high-flux dialysis setting by the addition of human serum albumin as a molecular adsorbent to the dialysate with subsequent recirculation of the dialysate over sorbents (molecular adsorbent recirculating system). The current knowledge about the albumin dialysis molecular adsorbent recirculating system is reviewed in this article.
- Published
- 2001
- Full Text
- View/download PDF
29. Use of human preconditioned phagocytes for extracorporeal immune support: introduction of a concept.
- Author
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Mitzner SR, Freytag J, Sauer M, Kleinfeldt T, Altrichter J, Klöhr S, Koball S, Stange J, Ringel B, Nebe B, Schmidt H, Podbielski A, Noeldge-Schomburg G, and Schmidt R
- Subjects
- Bioreactors, Candida albicans immunology, Cytokines biosynthesis, Escherichia coli immunology, HL-60 Cells immunology, Humans, In Vitro Techniques, Phagocytosis immunology, Sepsis immunology, Extracorporeal Circulation methods, Phagocytes immunology, Sepsis therapy
- Abstract
Neutrophils are critical effector cells in humoral and innate immunity and play a vital role in phagocytosis and bacterial killing. If they and/or their specific functions are lacking, then immunoparalysis may occur, and severe diseases like systemic inflammatory response syndrome (SIRS) or sepsis can take a fatal course. In this paper, we discuss the possibility of using preconditioned cells in an extracorporeal biohybrid immune support system. A human promyelocytic cell line was stimulated for different times with all-trans retinoic acid. The resulting cells displayed major signs and functions of mature neutrophilic granulocytes including oxygen radical production, phagocytosis of living and dead Escherichia coli, Staphylococcus aureus, Candida albicans, intracellular killing, and interleukin production. The cells can be expanded to yield a sufficient cell mass, and subsequent prestimulation results in an expression of specific neutrophil functions. Extracorporeal bioreactor experiments seem to be feasible to test the benefit in immunoparalysis-associated diseases like SIRS or sepsis.
- Published
- 2001
- Full Text
- View/download PDF
30. Improvement of multiple organ functions in hepatorenal syndrome during albumin dialysis with the molecular adsorbent recirculating system.
- Author
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Mitzner SR, Klammt S, Peszynski P, Hickstein H, Korten G, Stange J, and Schmidt R
- Subjects
- Adult, Chronic Disease, Extracorporeal Circulation methods, Female, Hemodialysis Solutions therapeutic use, Humans, Liver Diseases, Alcoholic blood, Liver Diseases, Alcoholic complications, Liver Diseases, Alcoholic therapy, Liver Failure, Acute blood, Liver Failure, Acute therapy, Male, Middle Aged, Albumins therapeutic use, Hepatorenal Syndrome blood, Hepatorenal Syndrome therapy, Multiple Organ Failure blood, Multiple Organ Failure therapy, Renal Dialysis methods
- Abstract
Recently, significant improvement of renal function and prolongation of survival were reported in hepatorenal syndrome (HRS) patients treated with the Molecular Adsorbent Recirculating System (MARS). As no impact on extrarenal organ function was documented, this trial looked into multiple organ function changes during MARS in HRS patients. Eight HRS patients (4 male, mean age 42.1 years, range 30-58, all United Network for Organ Sharing [UNOS] status 2A) were treated intermittendly 4-14 times (total 47, mean 5.9 +/- 3.4) between 4 and 8 h/single treatment. The following changes were observed pre- and posttreatment: bilirubin 466 +/- 146 to 284 +/- 134 micromol/L, creatinine 380 +/- 182 to 163 +/- 119 micromol/L, urea 26.4 +/- 10.3 to 12.9 +/- 4.9 mmol/L, plasma sodium 127.5 +/- 7.7 to 137.5 +/- 4.8 mmol/L (all p < 0.01). Mean arterial pressure (MAP) increased from 71.9 +/- 12.8 to 95.6 +/- 7.8 Torr (p < 0.001). Oliguria or anuria, present in all patients, was successfully reverted. Ascites, present in all patients, was not detectable after the treatment period. The hepatic encephalopathy grade decreased from 2.8 +/- 0.8 to 0.8 +/- 0.7 (p < 0.0001). Child-Index decreased from 13.25 +/- 1.3 to 9.4 +/- 1.8 (p < 0.001). The hospital survival rate was 62%. One man underwent successful liver transplantation 18 months after the treatment. We conclude that MARS can improve multiple organ functions in patients with HRS.
- Published
- 2001
- Full Text
- View/download PDF
31. Extracorporeal detoxification using the molecular adsorbent recirculating system for critically ill patients with liver failure.
- Author
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Mitzner SR, Stange J, Klammt S, Peszynski P, Schmidt R, and Nöldge-Schomburg G
- Subjects
- Humans, Liver Failure physiopathology, Critical Illness therapy, Liver Failure therapy, Sorption Detoxification methods
- Abstract
Liver failure resulting from different causes and its concomitant complications represent difficult-to-treat conditions with high mortality rates, despite improved therapeutic modalities in intensive care medicine. The accumulation of albumin-bound metabolites that are normally cleared by the liver, such as bilirubin and bile acids, contributes substantially to the development of multiorgan dysfunction in these clinical situations. The molecular adsorbent recirculating system (MARS) represents a cell-free, extracorporeal, liver assistance method for the selective removal of albumin-bound substances. Moreover, it enables the removal of excess water and water-soluble substances via an inbuilt dialysis step. Since 1993, >400 patients have been treated in 53 centers in Europe, the United States, and Asia. Diseases treated with MARS included acute exacerbation of chronic hepatic failure, hepatorenal syndrome, acute hepatic failure, and primary nonfunction/poor function after liver transplantation and major liver resection. Treatments were well tolerated. No severe adverse events were observed. Six- to 8-h MARS treatments resulted in significant (P < 0.05) removal of bilirubin, bile acids, tryptophan, short- and middle-chain fatty acids, aromatic amino acids, and ammonia. Clearance rates for strongly albumin-bound substances were between 10 and 60 ml/min. The removal of albumin-bound toxins resulted in decreases in hepatic encephalopathy, increases in mean arterial pressure, and improvements in kidney and liver function. In the first randomized clinical trial of the MARS method for treatment of the hepatorenal syndrome, significant prolongation of survival was observed for the MARS-treated group. It is concluded that the MARS method can contribute to the treatment of critically ill patients with liver failure and different underlying diseases.
- Published
- 2001
32. Liver support by extracorporeal blood purification: a clinical observation.
- Author
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Stange J, Mitzner SR, Klammt S, Freytag J, Peszynski P, Loock J, Hickstein H, Korten G, Schmidt R, Hentschel J, Schulz M, Löhr M, Liebe S, Schareck W, and Hopt UT
- Subjects
- Adult, Female, Humans, Liver Failure blood, Male, Middle Aged, Retrospective Studies, Treatment Outcome, Extracorporeal Circulation, Inactivation, Metabolic, Liver metabolism, Liver Failure metabolism, Renal Dialysis, Toxins, Biological blood
- Abstract
Liver failure associated with excretory insufficiency and jaundice results in an endogenous accumulation of toxins involved in the impairment of cardiovascular, kidney, and cerebral function. Moreover, these toxins have been shown to damage the liver itself by inducing hepatocellular apoptosis and necrosis, thus creating a vicious cycle of the disease. We report a retrospective cohort study of 26 patients with acute or chronic liver failure with intrahepatic cholestasis (bilirubin level > 20 mg/dL) who underwent a new extracorporeal blood purification treatment. A synthetic hydrophilic/hydrophobic domain-presenting semipermeable membrane (pore size < albumin size, 100-nm thick) was used for extracorporeal blood detoxification using dialysis equipment. The opposite side was rinsed with ligandin-like proteins as molecular adsorbents that were regenerated online using a chromatography-like recycling system (molecular adsorbent recirculating system [MARS]). Bile acid and bilirubin levels, representing the previously described toxins, were reduced by 16% to 53% and 10% to 90% of the initial concentration by a single treatment of 6 to 8 hours, respectively. Toxicity testing of patient plasma onto primary rat hepatocytes by live/dead fluorescence microscopy showed cell-damaging effects of jaundiced plasma that were not observed after treatment. Patients with a worsening of Child-Turcotte-Pugh (CTP) index before the treatments showed a significant improvement of this index during a period of 2 to 14 single treatments with an average of 14 days. After withdrawal of MARS treatment, this improvement was sustained in all long-term survivors. Ten patients represented a clinical status equivalent to the United Network for Organ Sharing (UNOS) status 2b (group A1), and all survived. Sixteen patients represented a clinical status equivalent to UNOS status 2a, and 7 of these patients survived (group A2), whereas 9 patients (group B) died. We conclude that in acute excretory failure caused by a chronic liver disease, this treatment provides a therapy option to remove toxins involved in multiorgan dysfunction secondary to liver failure.
- Published
- 2000
- Full Text
- View/download PDF
33. Improvement of hepatorenal syndrome with extracorporeal albumin dialysis MARS: results of a prospective, randomized, controlled clinical trial.
- Author
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Mitzner SR, Stange J, Klammt S, Risler T, Erley CM, Bader BD, Berger ED, Lauchart W, Peszynski P, Freytag J, Hickstein H, Loock J, Löhr JM, Liebe S, Emmrich J, Korten G, and Schmidt R
- Subjects
- Hepatorenal Syndrome mortality, Humans, Liver Cirrhosis complications, Prospective Studies, Survival Rate, Treatment Outcome, Albumins, Dialysis Solutions, Hepatorenal Syndrome therapy, Renal Dialysis methods
- Abstract
In hepatorenal syndrome (HRS), renal insufficiency is often progressive, and the prognosis is extremely poor under standard medical therapy. The molecular adsorbent recirculating system (MARS) is a modified dialysis method using an albumin-containing dialysate that is recirculated and perfused online through charcoal and anion-exchanger columns. MARS enables the selective removal of albumin-bound substances. A prospective controlled trial was performed to determine the effect of MARS treatment on 30-day survival in patients with type I HRS at high risk (bilirubin level, > or =15 mg/dL) compared with standard treatment. Thirteen patients with cirrhosis with type I HRS were included from 1997 to 1999. All were Child's class C, with Child-Turcotte-Pugh scores of 12.4 +/- 1. 0, United Network for Organ Sharing status 2A, and total bilirubin values of 25.7 +/- 14.0 mg/dL. Eight patients were treated with the MARS method in addition to hemodiafiltration (HDF) and standard medical therapy, and 5 patients were in the control group (HDF and standard medical treatment alone). None of these patients underwent liver transplantation or received a transjugular intrahepatic portosystemic shunt or vasopressin analogues during the observation period. In the MARS group, 5.2 +/- 3.6 treatments (range, 1 to 10 treatments) were performed for 6 to 8 hours daily per patient. A significant decrease in bilirubin and creatinine levels (P <.01) and increase in serum sodium level and prothrombin activity (P <.01) were observed in the MARS group. Mortality rates were 100% in the control group at day 7 and 62.5% in the MARS group at day 7 and 75% at day 30, respectively (P <.01). We conclude that the removal of albumin-bound substances with the MARS method can contribute to the treatment of type I HRS.
- Published
- 2000
- Full Text
- View/download PDF
34. Molecular adsorbent recycling system (MARS): clinical results of a new membrane-based blood purification system for bioartificial liver support.
- Author
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Stange J, Mitzner SR, Risler T, Erley CM, Lauchart W, Goehl H, Klammt S, Peszynski P, Freytag J, Hickstein H, Löhr M, Liebe S, Schareck W, Hopt UT, and Schmidt R
- Subjects
- Adsorption, Adult, Ammonia blood, Bilirubin blood, Cholinesterases blood, Creatinine blood, Female, Hepatic Encephalopathy blood, Hepatic Encephalopathy mortality, Hepatic Encephalopathy therapy, Humans, Liver Failure blood, Liver Failure mortality, Male, Membranes, Artificial, Middle Aged, Protein Binding, Serum Albumin metabolism, Survival Rate, Urea blood, Liver Failure therapy, Liver, Artificial, Renal Dialysis methods
- Abstract
The use of xenogenic or genetically engineered cell types in bioartificial liver support systems requires separation methods between the patients' blood and the liver support bioreactors that guarantee the sufficient transfer of pathophysiologically relevant substances but prevent complications. The present paper describes a new membrane separation system that is nearly impermeable to proteins but enables the exchange of water soluble and protein bound toxins by a special membrane and a recycled protein containing dialysate. Because the full range of toxins in hepatic failure has still not been identified, the value of this membrane separation method was evaluated clinically. Thirteen patients suffering from life threatening hepatic failure who had not responded to state of the art therapy were treated with this device, the molecular adsorbent recycling system (MARS). The overall survival rate was 69%. All patients showed positive response to the therapy, indicating that the presented membrane separator combines therapeutic effectivity with the highest safety criteria for the patient by cutting the exchange of substances below the level of proteins.
- Published
- 1999
- Full Text
- View/download PDF
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