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T Felbinger

Publications and source records attributed to T Felbinger.

6 recordsLinked to original sources
PubMed2000

Classical information and distillable entanglement

We establish a quantitative connection between the amount of lost classical information about a quantum state and the concomitant loss of entanglement. Using methods that have been developed for the optimal purification of mixed states, we find a class of mixed states with known distillable entanglement. These results can be used to determine the quantum capacity of a quantum channel which randomizes the order of transmitted signals.

Journal Article↗
PubMed2000

IG-therasorb immunoapheresis in orthotopic xenotransplantation of baboons with landrace pig hearts.

BACKGROUND: The major problem of xenotransplantation is, that hyperacute xenograft rejection (HXR) causes graft failure within minutes or a few hours because of natural antibodies and activation of the complement system. As a preclinical model we transplanted pig hearts orthotopically into baboons. To prevent HXR after orthotopic xenotransplantation (oXHTx), the immunoglobulins (Ig) and natural antibodies were adsorbed to reusable Ig-Therasorb immunoadsorption (IA) columns. METHODS: We performed three oXHTx of landrace pig hearts into baboons (19+/-6.8 kg), using extracorporeal circulation (ECC) connected to the IA unit. After separating the recipient's blood into plasma and cellular fraction by a plasma filter, plasma flow was directed to the Ig-Therasorb column coated with polyclonal sheep-antibodies against human IgG, IgM, and IgA. Intraoperative treatment consisted of 4 cycles of IA. For a control, we transplanted one pig heart into a baboon (16.9 kg) without applying IA. Perioperatively, serum concentrations of Ig, anti-pig-antibodies, complement and cardiac enzymes were determined. Tissue samples of myocardium were collected at the end of the study for immunohistochemical examinations, light microscopic examination (LM) and electron microscopic examination (EM). For cardiac monitoring after oXHTx, we used ECG, echocardiography, and invasive measurement of cardiac output. To prevent a mismatch of donor and recipient heart size, the donor pig had a 30-40% lower body weight than the recipient baboon. RESULTS: Four cycles of IA removed >80% of IgG, IgM, and IgA from plasma. The graft of the control animal failed after 29 min. The first oXHTx with IA was intentionally terminated after 100 min, the second oXHTx after 11 hr and the third oXHTx after 21 hr. All xenografts showed no histological signs of HXR. After weaning off ECC, these donor hearts worked in sinus rhythm without electrocardiographic ST-segment elevation. An excellent cardiac output was measured by echocardiography and thermodilution (2 L/min). Serological parameters indicating cardiac damage were significantly lower after IA if compared with the control experiment. Macroscopically, the xenograft of the control animal showed massive hemorrhage in comparison with the almost inconspicuous grafts after IA. The myocardium of the IA group demonstrated fewer deposits of Ig and complement components compared with the control animal. CONCLUSION: Baboons do not hyperacutely reject a porcine xenograft after antibody depletion by the Ig-Therasorb column. In our experiment only 4 cycles of immunoapheresis effectively prevented HXR after oXHTx of baboons. The Ig-Therasorb column is a reusable device, which can be handled easily in combination with the ECC. IA must be tested in oXHTx longterm survival experiments, especially in combination with transgenic pig organs, which could be a reliable preclinical approach for future clinical xenotransplantation.

Animals↗
PubMed2000

Prevention of hyperacute xenograft rejection in orthotopic xenotransplantation of pig hearts into baboons using immunoadsorption of antibodies and complement factors.

To prevent hyperacute xenograft rejection (HXR) caused by preformed natural antibodies (XNAb) after orthotopic heart xenotransplantation (oXHTx) of landrace pig hearts into baboons, we used immunoadsorption of immunoglobulins IgG, IgM and IgA and complement with the reusable Ig-Therasorb column. In addition to functional data, tissue was sampled for histological, immunohistochemical and electron microscopical analysis. We performed three oXHTx of landrace pig hearts to baboons using extracorporeal circulation (ECC) connected to the immunoadsorption unit. Intraoperative treatment consisted of four cycles of immunoabsorption (IA). One oXHTx of a baboon without IA served as a control. A mismatch of donor and recipient heart size was prevented by selecting a 30-40% lower body weight of donor pigs than recipients. Four cycles of IA removed more than 80% of IgG, IgM and IgA, 86% of antipig antibodies and 66% of complement factors C3 and C4 from plasma. The graft of the control animal failed after 29 min. Orthotopic xenotransplantation with IA was selectively terminated after 100 min, 11 h and 21 h, respectively without any histological signs of HXR in light and electron microscopy. After weaning off from ECC these donor xenografts showed sufficient function with normal ECG and excellent cardiac output in echocardiography and invasive measurement (1.93 +/- 0.035 l/min). The myocardium of the control xenograft demonstrated more deposits of Ig and complement components (C3, C4) than in the IA group. Baboons survive HXR after orthotopic pig heart xenotransplantation due to antibody depletion by reusable Ig-Therasorb column treatment. Long-term survival in an orthotopic baboon xenotransplantation model after IA, especially in combination with transgenic pig organs, could be a reliable preclinical trial for future clinical xenotransplantation programs.

Acute Disease↗
PubMedDate not supplied

Mean xenograft survival of 14.6 days in a small group of hDAF-transgenic pig hearts transplanted orthotopically into baboons.

INTRODUCTION: In a discordant orthotopic xenotransplantation model (pig-to-baboon) donor pigs expressing human decay accelerating factor (hDAF) as a regulator of complement activity were used to prevent hyperacute xenograft rejection (HXR). We investigated a modified immunosuppressive therapy consisting of ERL080 (Novartis Pharma AG, Base, Switzerland), cyclosporin A (Neoral), steroids, and a cyclophosphamide (CyP) induction protocol with several reduced doses to prevent acute vascular rejection (AVR). METHODS: Donor hearts were harvested from hDAF-transgenic pigs (18.8 +/- 2.6 kg, Imutran Ltd., a Novartis Pharma AG Company). Four adult baboons (25.6 +/- 2.7 kg) with high titers of xenoreactive antibodies (XAb) served as recipients. Serological and hemodynamic parameters were measured. Finally, myocardial tissue was sampled for histological and immunohistochemical examinations. RESULTS: In the first baboon, an acute graft failure occurred after 1 hour due to preservation injury. The second succumbed after 11.1 day due to an acute renal failure. The third died after 13.1 days of an ileus. The fourth baboon had continuously excellent cardiac function (mean echocardiographic ejection fraction, 69.2%), but succumbed on day 20 due to anemia. Corrected mean xenograft survival (excluding the first baboon because of a technical failure) was 14.6 +/- 2.6 days. XAb decreased after day 3 to constantly low levels (<1:64 titer) after CyP induction. White blood cell count decreased from 10.3 +/- 0.8 to 0.9 +/- 0.3 G/L after day 3. Macroscopically and histologically no typical signs of HXR or severe AVR could be detected. CONCLUSIONS: These results confirm that hDAF transgen blocks HXR in this life-supporting model. AVR was prevented by using a modified quadruple immunosuppressive drug combination (Neoral, ERL080, steroids, and several small single doses of CyP). An optimum "fine-tuning" of immunosuppression is required to achieve the best risk-benefit ratio.

Animals↗
PubMedDate not supplied

Combination of hDAF-transgenic pig hearts and immunoadsorption in heterotopic xenotransplantation of immunosuppressed baboons.

INTRODUCTION: Hyperacute xenograft rejection (HXR) and acute vascular rejection (AVR) after xenotransplantation are triggered by xenoreactive antibodies (XAb) and an activated complement cascade. In a heterotopic (abdominal) xenotransplantation model we combined immunoadsorption (IA, Ig-Therasorb column) and a quadruple immunosuppressive drug therapy in recipient baboons with donor pig hearts transgenic for human decay accelerating factor (hDAF). METHODS: According to XAb titers between 6 and 14 cycles of IA were performed preoperatively in 4 recipient baboons (18.6 +/- 2.5 kg). Hearts of hDAF-transgenic donor pigs (6.1 +/- 1.1 kg, Imutran Ltd., a Novartis Pharma AG Company, Basel, Switzerland) were heterotopically transplanted using the abdominal technique in baboons. Immunosuppression consisted of cyclophosphamide (CyP) induction therapy, ERL080 (Novartis Pharma AG), cyclosporin A (CyA, Neoral), and steroids. Blood levels of mycophenolate, CyA, immunoglobulins (Ig), anti-pig-antibodies, complement factors, and cardiac enzymes were determined. Abdominal electrocardiography (ECG), echocardiography, and palpation were used for monitoring of the pig hearts. Myocardial tissue specimens were examined using immunohistochemistry, light microscope (LM), and electron microscope (EM). RESULTS: Ten cycles of IA alone removed 78% of XAb and accordingly IgM, IgG, IgA, complement C3, and C4. None of the xenografts was hyperacutely rejected, but xenograft failure occurred after 5.0 +/- 1.3 days (range, 2.4-8.0 days) because of an AVR associated with a rapid XAb increase within 24 hours. White blood cell count (10.3 +/- 2.2 G/L) showed a maximum of 13.1 +/- 2.1 (day 1) and constant levels (1.4 +/- 0.3-2.1 +/- 1.3 G/L) between day 3 and 6. Histology (LM/EM) showed massive hemorrhage, necrosis, and vascular thrombi as signs of AVR. CONCLUSION: Although HXR was prevented by using IA and hDAF-transgenic donor hearts, AVR was not avoided due to insufficient immunosuppressive regimen used and a missed postoperative IA treatment as a result of an inefficient control of XAb production.

Adrenal Cortex Hormones↗