The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Robert P Frantz - One of the best experts on this subject based on the ideXlab platform.
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sirolimus as primary immunosuppression attenuates allograft vasculopathy with improved late survival and decreased cardiac events after cardiac transplantation
Circulation, 2012Co-Authors: Yan Topilsky, Eugenia Raichlin, Tal Hasin, Barry A Boilson, John A Schirger, Richard J Rodeheffer, Alfredo L Clavell, Brooks Sayre Edwards, Naveen Luke Pereira, Robert P FrantzAbstract:Background—We retrospectively analyzed the potential of sirolimus as a primary immunosuppressant in the long-term attenuation of cardiac allograft vasculopathy progression and the effects on cardiac-related morbidity and mortality. Methods and Results—Forty-five cardiac transplant recipients were converted to sirolimus 1.2 years (0.2, 4.0) after transplantation with complete calcineurin inhibitor withdrawal. Fifty-eight control subjects 2.0 years (0.2, 6.5 years) from transplantation were maintained on calcineurin inhibitors. Age, sex, ejection fraction, and time from transplantation to baseline intravascular ultrasound study were not different (P>0.2 for all) between the groups; neither were secondary Immunosuppressants and use of steroids. Three-dimensional intravascular ultrasound studies were performed at baseline and 3.1 years (1.3, 4.6 years) later. Plaque index progression (plaque volume/vessel volume) was attenuated in the sirolimus group (0.7±10.5% versus 9.3±10.8%; P=0.0003) owing to reduced pla...
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conversion to sirolimus as primary immunosuppression attenuates the progression of allograft vasculopathy after cardiac transplantation
Circulation, 2007Co-Authors: Eugenia Raichlin, Walter K Kremers, Zain Khalpey, Robert P Frantz, Richard J Rodeheffer, Alfredo L Clavell, Brooks Sayre Edwards, Amir Lerman, Charanjit S Rihal, Sudhir S KushwahaAbstract:Background— We investigated the potential of conversion to sirolimus (SRL) as a primary immunosuppressant in attenuating cardiac allograft vasculopathy progression. Methods and Results— Twenty-nine cardiac transplant recipients were converted to SRL 3.8±3.4 years after transplantation with complete calcineurin inhibitor (CNI) withdrawal. Secondary Immunosuppressants (azathioprine or mycophenolate) and steroids remained unchanged. Forty patients (controls) 4.8±4.0 years from transplantation were maintained on CNIs. Three-dimensional intravascular ultrasound studies were performed at baseline and 12.1±2.6 months later. Mean plaque (media and intima) volume (PV) and plaque index (PI) (PV/vessel volume percent) increased significantly in the CNI group (1.28±2.86 mm3/mm, P=0.004; and 6±8%, P=0.0001) but not in the SRL group (0.1±1.13 mm3/mm, P=0.63; and 0.1±8%, P=0.94). In patients enrolled within 2 years after transplantation, the increases in PV (0.06±1.06 versus 1.77±1.65 mm3/mm; P=0.0081) and PI (0±9% vers...
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sirolimus in cardiac transplantation use as a primary immunosuppressant in calcineurin inhibitor induced nephrotoxicity
Journal of Heart and Lung Transplantation, 2005Co-Authors: Sudhir S Kushwaha, Zain Khalpey, Robert P Frantz, Richard J Rodeheffer, Alfredo L Clavell, Richard C Daly, Christopher G A Mcgregor, Brooks S EdwardsAbstract:Background Calcineurin inhibitor (CNI) Immunosuppressants are a major cause of renal dysfunction in cardiac transplant recipients, leading to increased morbidity and mortality. The aim of this study was to evaluate the efficacy and safety of CNI withdrawal and substitution with sirolimus as the primary immunosuppressant, and assess the effect on renal function in cardiac transplant recipients with CNI-induced renal impairment. Methods Thirty-four stable cardiac transplant recipients (range 1 to 14 years post-transplant) with CNI-induced nephrotoxicity (iothalamate clearance 25 to 50 ml/min) or cardiac allograft vasculopathy (CAV) were enrolled. Twelve patients (Group A) were prospectively enrolled for renal dysfunction. The remaining patients ( n = 22, Group B) were converted to sirolimus on clinical grounds because of poor renal function or the presence of CAV. CNI was withdrawn gradually over 12 weeks. Sirolimus was started at 1 mg/day with titration over 2 weeks to achieve levels of 10 to 15 ng/ml. Echocardiograms and cardiac biopsies were performed to determine rejection. Adjunct immunosuppression was left unchanged. Follow-up iothalamate clearance was performed. A further 24 patients (Group C) were retrospective controls, stable (range 2 to 10 years post-transplant), and maintained on a standard CNI-based immunosuppressant regimen. Results Iothalamate clearance (C i ) improved significantly (Group A baseline: 36.08 ± 2.4 ml/min to 48.67 ± 4.1 ml/min, p = 0.004; Group B baseline: 48.14 ± 3.2 ml/min to 55.77 ± 4.2 ml/min, p p Conclusions Substitution of CNIs with sirolimus in cardiac transplant recipients is safe and effective and leads to an improvement in renal function, without compromise in cardiac function and rejection.
Peter I Pillans - One of the best experts on this subject based on the ideXlab platform.
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the current role of liquid chromatography tandem mass spectrometry in therapeutic drug monitoring of immunosuppressant and antiretroviral drugs
Clinical Biochemistry, 2011Co-Authors: Paul J Taylor, Chunhui Tai, Michael E Franklin, Peter I PillansAbstract:Therapeutic drug monitoring of critical dose immunosuppressant drugs is established clinical practice and there are similar good reasons to monitor antiretrovirals. The aim of this article is to review the recent literature (last five years), with particular reference to the use of liquid chromatography-tandem mass spectrometry (LC-MS/MS). LC-MS/MS offers many potential advantages. The superior selectivity of LC-MS/MS over immunoassays for immunosuppressant drugs has been widely reported. Simultaneous measurement of a number of drugs can be performed. It is currently routine practice for the four major Immunosuppressants (cyclosporin, tacrolimus, sirolimus and everolimus) to be simultaneously measured in whole blood. While up to 17 antiretroviral drugs have been simultaneously measured in plasma. The exquisite sensitivity of LC-MS/MS also provides the opportunity to measure these drugs in alternative matrices, such as dried blood spots, saliva, peripheral blood mononuclear cells and tissue. However, the clinical utility of measuring these classes of drugs in alternative matrices is still to be determined.
Andrew N Hoofnagle - One of the best experts on this subject based on the ideXlab platform.
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liquid chromatography tandem mass spectrometry work flow for parallel quantification of methotrexate and other Immunosuppressants
Clinical Chemistry, 2012Co-Authors: Hari Nair, Lisa Lawrence, Andrew N HoofnagleAbstract:To the Editor: Methotrexate is a potentially toxic folic acid antagonist that is widely used as an immunosuppressant and chemotherapeutic agent. After high doses (0.035–12 g/m2) are administered, methotrexate concentrations in the plasma or serum are carefully monitored so that the patient can be rescued, if necessary, with the proper dose of leucovorin, a folic acid analog that bypasses the important enzymes inhibited by methotrexate (1). Recently, the manufacturer of the fluorescence polarization immunoassay we use for monitoring (TDX platform; Abbott Laboratories) announced its intention to move the assay to a different proprietary platform. In addition, the immunoassay is known to be nonspecific. For example, the assay strongly cross-reacts with diamino- N 10-methylpteroic acid, a minor ( 98%) product of pharmacologic inactivation of methotrexate with carboxypeptidase G2 (2). As an alternative to reagent-dependent proprietary methods, a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method, with an improved specificity, can be used to measure methotrexate (2, 3). Many laboratories, including our own, have replaced immunoassays for other Immunosuppressants, which can also suffer from interferences, with laboratory-developed tests that use LC-MS/MS (4). In contrast to methotrexate, the number of samples processed for other Immunosuppressants with the immunosuppressant assay is high enough to support the LC-MS/MS infrastructure in …
Sudhir S Kushwaha - One of the best experts on this subject based on the ideXlab platform.
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conversion to sirolimus as primary immunosuppression attenuates the progression of allograft vasculopathy after cardiac transplantation
Circulation, 2007Co-Authors: Eugenia Raichlin, Walter K Kremers, Zain Khalpey, Robert P Frantz, Richard J Rodeheffer, Alfredo L Clavell, Brooks Sayre Edwards, Amir Lerman, Charanjit S Rihal, Sudhir S KushwahaAbstract:Background— We investigated the potential of conversion to sirolimus (SRL) as a primary immunosuppressant in attenuating cardiac allograft vasculopathy progression. Methods and Results— Twenty-nine cardiac transplant recipients were converted to SRL 3.8±3.4 years after transplantation with complete calcineurin inhibitor (CNI) withdrawal. Secondary Immunosuppressants (azathioprine or mycophenolate) and steroids remained unchanged. Forty patients (controls) 4.8±4.0 years from transplantation were maintained on CNIs. Three-dimensional intravascular ultrasound studies were performed at baseline and 12.1±2.6 months later. Mean plaque (media and intima) volume (PV) and plaque index (PI) (PV/vessel volume percent) increased significantly in the CNI group (1.28±2.86 mm3/mm, P=0.004; and 6±8%, P=0.0001) but not in the SRL group (0.1±1.13 mm3/mm, P=0.63; and 0.1±8%, P=0.94). In patients enrolled within 2 years after transplantation, the increases in PV (0.06±1.06 versus 1.77±1.65 mm3/mm; P=0.0081) and PI (0±9% vers...
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sirolimus in cardiac transplantation use as a primary immunosuppressant in calcineurin inhibitor induced nephrotoxicity
Journal of Heart and Lung Transplantation, 2005Co-Authors: Sudhir S Kushwaha, Zain Khalpey, Robert P Frantz, Richard J Rodeheffer, Alfredo L Clavell, Richard C Daly, Christopher G A Mcgregor, Brooks S EdwardsAbstract:Background Calcineurin inhibitor (CNI) Immunosuppressants are a major cause of renal dysfunction in cardiac transplant recipients, leading to increased morbidity and mortality. The aim of this study was to evaluate the efficacy and safety of CNI withdrawal and substitution with sirolimus as the primary immunosuppressant, and assess the effect on renal function in cardiac transplant recipients with CNI-induced renal impairment. Methods Thirty-four stable cardiac transplant recipients (range 1 to 14 years post-transplant) with CNI-induced nephrotoxicity (iothalamate clearance 25 to 50 ml/min) or cardiac allograft vasculopathy (CAV) were enrolled. Twelve patients (Group A) were prospectively enrolled for renal dysfunction. The remaining patients ( n = 22, Group B) were converted to sirolimus on clinical grounds because of poor renal function or the presence of CAV. CNI was withdrawn gradually over 12 weeks. Sirolimus was started at 1 mg/day with titration over 2 weeks to achieve levels of 10 to 15 ng/ml. Echocardiograms and cardiac biopsies were performed to determine rejection. Adjunct immunosuppression was left unchanged. Follow-up iothalamate clearance was performed. A further 24 patients (Group C) were retrospective controls, stable (range 2 to 10 years post-transplant), and maintained on a standard CNI-based immunosuppressant regimen. Results Iothalamate clearance (C i ) improved significantly (Group A baseline: 36.08 ± 2.4 ml/min to 48.67 ± 4.1 ml/min, p = 0.004; Group B baseline: 48.14 ± 3.2 ml/min to 55.77 ± 4.2 ml/min, p p Conclusions Substitution of CNIs with sirolimus in cardiac transplant recipients is safe and effective and leads to an improvement in renal function, without compromise in cardiac function and rejection.
Richard J Rodeheffer - One of the best experts on this subject based on the ideXlab platform.
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sirolimus as primary immunosuppression attenuates allograft vasculopathy with improved late survival and decreased cardiac events after cardiac transplantation
Circulation, 2012Co-Authors: Yan Topilsky, Eugenia Raichlin, Tal Hasin, Barry A Boilson, John A Schirger, Richard J Rodeheffer, Alfredo L Clavell, Brooks Sayre Edwards, Naveen Luke Pereira, Robert P FrantzAbstract:Background—We retrospectively analyzed the potential of sirolimus as a primary immunosuppressant in the long-term attenuation of cardiac allograft vasculopathy progression and the effects on cardiac-related morbidity and mortality. Methods and Results—Forty-five cardiac transplant recipients were converted to sirolimus 1.2 years (0.2, 4.0) after transplantation with complete calcineurin inhibitor withdrawal. Fifty-eight control subjects 2.0 years (0.2, 6.5 years) from transplantation were maintained on calcineurin inhibitors. Age, sex, ejection fraction, and time from transplantation to baseline intravascular ultrasound study were not different (P>0.2 for all) between the groups; neither were secondary Immunosuppressants and use of steroids. Three-dimensional intravascular ultrasound studies were performed at baseline and 3.1 years (1.3, 4.6 years) later. Plaque index progression (plaque volume/vessel volume) was attenuated in the sirolimus group (0.7±10.5% versus 9.3±10.8%; P=0.0003) owing to reduced pla...
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conversion to sirolimus as primary immunosuppression attenuates the progression of allograft vasculopathy after cardiac transplantation
Circulation, 2007Co-Authors: Eugenia Raichlin, Walter K Kremers, Zain Khalpey, Robert P Frantz, Richard J Rodeheffer, Alfredo L Clavell, Brooks Sayre Edwards, Amir Lerman, Charanjit S Rihal, Sudhir S KushwahaAbstract:Background— We investigated the potential of conversion to sirolimus (SRL) as a primary immunosuppressant in attenuating cardiac allograft vasculopathy progression. Methods and Results— Twenty-nine cardiac transplant recipients were converted to SRL 3.8±3.4 years after transplantation with complete calcineurin inhibitor (CNI) withdrawal. Secondary Immunosuppressants (azathioprine or mycophenolate) and steroids remained unchanged. Forty patients (controls) 4.8±4.0 years from transplantation were maintained on CNIs. Three-dimensional intravascular ultrasound studies were performed at baseline and 12.1±2.6 months later. Mean plaque (media and intima) volume (PV) and plaque index (PI) (PV/vessel volume percent) increased significantly in the CNI group (1.28±2.86 mm3/mm, P=0.004; and 6±8%, P=0.0001) but not in the SRL group (0.1±1.13 mm3/mm, P=0.63; and 0.1±8%, P=0.94). In patients enrolled within 2 years after transplantation, the increases in PV (0.06±1.06 versus 1.77±1.65 mm3/mm; P=0.0081) and PI (0±9% vers...
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sirolimus in cardiac transplantation use as a primary immunosuppressant in calcineurin inhibitor induced nephrotoxicity
Journal of Heart and Lung Transplantation, 2005Co-Authors: Sudhir S Kushwaha, Zain Khalpey, Robert P Frantz, Richard J Rodeheffer, Alfredo L Clavell, Richard C Daly, Christopher G A Mcgregor, Brooks S EdwardsAbstract:Background Calcineurin inhibitor (CNI) Immunosuppressants are a major cause of renal dysfunction in cardiac transplant recipients, leading to increased morbidity and mortality. The aim of this study was to evaluate the efficacy and safety of CNI withdrawal and substitution with sirolimus as the primary immunosuppressant, and assess the effect on renal function in cardiac transplant recipients with CNI-induced renal impairment. Methods Thirty-four stable cardiac transplant recipients (range 1 to 14 years post-transplant) with CNI-induced nephrotoxicity (iothalamate clearance 25 to 50 ml/min) or cardiac allograft vasculopathy (CAV) were enrolled. Twelve patients (Group A) were prospectively enrolled for renal dysfunction. The remaining patients ( n = 22, Group B) were converted to sirolimus on clinical grounds because of poor renal function or the presence of CAV. CNI was withdrawn gradually over 12 weeks. Sirolimus was started at 1 mg/day with titration over 2 weeks to achieve levels of 10 to 15 ng/ml. Echocardiograms and cardiac biopsies were performed to determine rejection. Adjunct immunosuppression was left unchanged. Follow-up iothalamate clearance was performed. A further 24 patients (Group C) were retrospective controls, stable (range 2 to 10 years post-transplant), and maintained on a standard CNI-based immunosuppressant regimen. Results Iothalamate clearance (C i ) improved significantly (Group A baseline: 36.08 ± 2.4 ml/min to 48.67 ± 4.1 ml/min, p = 0.004; Group B baseline: 48.14 ± 3.2 ml/min to 55.77 ± 4.2 ml/min, p p Conclusions Substitution of CNIs with sirolimus in cardiac transplant recipients is safe and effective and leads to an improvement in renal function, without compromise in cardiac function and rejection.
