79 results on '"Marks WH"'
Search Results
2. Integrating innovation as a core objective in medical training.
- Author
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Boms O, Shi Z, Mallipeddi N, Chung JJ, Marks WH, Whitehead DC, and Succi MD
- Published
- 2022
- Full Text
- View/download PDF
3. Safety and efficacy of eculizumab in the prevention of antibody-mediated rejection in living-donor kidney transplant recipients requiring desensitization therapy: A randomized trial.
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Marks WH, Mamode N, Montgomery RA, Stegall MD, Ratner LE, Cornell LD, Rowshani AT, Colvin RB, Dain B, Boice JA, and Glotz D
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- Adolescent, Adult, Aged, Complement Inactivating Agents therapeutic use, Female, Follow-Up Studies, Graft Rejection etiology, Graft Rejection pathology, Graft Survival immunology, Histocompatibility Testing, Humans, Kidney Failure, Chronic immunology, Kidney Failure, Chronic therapy, Living Donors, Male, Middle Aged, Patient Safety, Prognosis, Risk Factors, Survival Rate, Young Adult, Antibodies, Monoclonal, Humanized therapeutic use, Desensitization, Immunologic methods, Graft Rejection prevention & control, Graft Survival drug effects, Isoantibodies adverse effects, Kidney Failure, Chronic mortality, Kidney Transplantation adverse effects
- Abstract
We report results of a phase 2, randomized, multicenter, open-label, two-arm study evaluating the safety and efficacy of eculizumab in preventing acute antibody-mediated rejection (AMR) in sensitized recipients of living-donor kidney transplants requiring pretransplant desensitization (NCT01399593). In total, 102 patients underwent desensitization. Posttransplant, 51 patients received standard of care (SOC) and 51 received eculizumab. The primary end point was week 9 posttransplant treatment failure rate, a composite of: biopsy-proven acute AMR (Banff 2007 grade II or III; assessed by blinded central pathology); graft loss; death; or loss to follow-up. Eculizumab was well tolerated with no new safety concerns. No significant difference in treatment failure rate was observed between eculizumab (9.8%) and SOC (13.7%; P = .760). To determine whether data assessment assumptions affected study outcome, biopsies were reanalyzed by central pathologists using clinical information. The resulting treatment failure rates were 11.8% and 21.6% for the eculizumab and SOC groups, respectively (nominal P = .288). When reassessment included grade I AMR, the treatment failure rates were 11.8% (eculizumab) and 29.4% (SOC; nominal P = .048). This finding suggests a potential benefit for eculizumab compared with SOC in preventing acute AMR in recipients sensitized to their living-donor kidney transplants (EudraCT 2010-019630-28)., (© 2019 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Published
- 2019
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4. Safety and efficacy of eculizumab for the prevention of antibody-mediated rejection after deceased-donor kidney transplantation in patients with preformed donor-specific antibodies.
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Glotz D, Russ G, Rostaing L, Legendre C, Tufveson G, Chadban S, Grinyó J, Mamode N, Rigotti P, Couzi L, Büchler M, Sandrini S, Dain B, Garfield M, Ogawa M, Richard T, and Marks WH
- Subjects
- Adolescent, Adult, Aged, Female, Follow-Up Studies, Graft Rejection etiology, Graft Rejection pathology, Graft Survival immunology, Humans, Kidney Failure, Chronic immunology, Kidney Failure, Chronic therapy, Male, Middle Aged, Patient Safety, Prognosis, Risk Factors, Survival Rate, Tissue Donors supply & distribution, Young Adult, Antibodies, Monoclonal, Humanized therapeutic use, Complement Inactivating Agents therapeutic use, Graft Rejection drug therapy, Graft Survival drug effects, Isoantibodies adverse effects, Kidney Failure, Chronic mortality, Kidney Transplantation adverse effects
- Abstract
The presence of preformed donor-specific antibodies in transplant recipients increases the risk of acute antibody-mediated rejection (AMR). Results of an open-label single-arm trial to evaluate the safety and efficacy of eculizumab in preventing acute AMR in recipients of deceased-donor kidney transplants with preformed donor-specific antibodies are reported. Participants received eculizumab as follows: 1200 mg immediately before reperfusion; 900 mg on posttransplant days 1, 7, 14, 21, and 28; and 1200 mg at weeks 5, 7, and 9. All patients received thymoglobulin induction therapy and standard maintenance immunosuppression including steroids. The primary end point was treatment failure rate, a composite of biopsy-proved grade II/III AMR (Banff 2007 criteria), graft loss, death, or loss to follow-up, within 9 weeks posttransplant. Eighty patients received transplants (48 women); the median age was 52 years (range 24-70 years). Observed treatment failure rate (8.8%) was significantly lower than expected for standard care (40%; P < .001). By 9 weeks, 3 of 80 patients had experienced AMR, and 4 of 80 had experienced graft loss. At 36 months, graft and patient survival rates were 83.4% and 91.5%, respectively. Eculizumab was well tolerated and no new safety concerns were identified. Eculizumab has the potential to provide prophylaxis against injury caused by acute AMR in such patients (EudraCT 2010-019631-35)., (© 2019 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Published
- 2019
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5. Longitudinal studies of a B cell-derived signature of tolerance in renal transplant recipients.
- Author
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Newell KA, Asare A, Sanz I, Wei C, Rosenberg A, Gao Z, Kanaparthi S, Asare S, Lim N, Stahly M, Howell M, Knechtle S, Kirk A, Marks WH, Kawai T, Spitzer T, Tolkoff-Rubin N, Sykes M, Sachs DH, Cosimi AB, Burlingham WJ, Phippard D, and Turka LA
- Subjects
- Adult, Allografts, B-Lymphocytes immunology, Female, Flow Cytometry, Gene Expression Profiling, Graft Rejection genetics, Graft Survival genetics, Humans, Kidney Transplantation methods, Longitudinal Studies, Male, Middle Aged, Prognosis, Registries, Risk Assessment, Transplant Recipients, Transplantation Immunology genetics, Transplantation Tolerance immunology, Treatment Outcome, B-Cell Activating Factor genetics, Gene Expression Regulation, Immunologic Memory genetics, Kidney Transplantation adverse effects, Transplantation Tolerance genetics
- Abstract
Biomarkers of transplant tolerance would enhance the safety and feasibility of clinical tolerance trials and potentially facilitate management of patients receiving immunosuppression. To this end, we examined blood from spontaneously tolerant renal transplant recipients and patients enrolled in two interventional tolerance trials using flow cytometry and gene expression profiling. Using a previously reported tolerant cohort as well as newly identified tolerant patients, we confirmed our previous finding that tolerance was associated with increased expression of B cell-associated genes relative to immunosuppressed patients. This was not accounted for merely by an increase in total B cell numbers, but was associated with the increased frequencies of transitional and naïve B cells. Moreover, serial measurements of gene expression demonstrated that this pattern persisted over several years, although patients receiving immunosuppression also displayed an increase in the two most dominant tolerance-related B cell genes, IGKV1D-13 and IGLL-1, over time. Importantly, patients rendered tolerant via induction of transient mixed chimerism, and those weaned to minimal immunosuppression, showed similar increases in IGKV1D-13 as did spontaneously tolerant individuals. Collectively, these findings support the notion that alterations in B cells may be a common theme for tolerant kidney transplant recipients, and that it is a useful monitoring tool in prospective trials., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Published
- 2015
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6. Hydrogel encapsulation to improve cell viability during syringe needle flow.
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Wagner MA, Marks WH, and Bhatia SK
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- Algorithms, Animals, Biomechanical Phenomena, Capsules, Cell Culture Techniques, Cell Membrane physiology, Cell Proliferation, Cell Survival physiology, Cells, Cultured, Drug Compounding, Electric Conductivity, Finite Element Analysis, Hydrogel, Polyethylene Glycol Dimethacrylate chemistry, Injections instrumentation, Materials Testing, Mice, Multipotent Stem Cells physiology, Nanotubes, Carbon chemistry, Phase Transition, Pressure, Rheology, Stem Cell Transplantation instrumentation, Stress, Mechanical, Multipotent Stem Cells transplantation, Needles, Poloxamer chemistry, Syringes, Tissue Scaffolds chemistry
- Abstract
This work examines pluronic F-127 poloxamer for cell protection during injection through a syringe needle. Direct cell injection is a minimally invasive method for cell transplantation; however, it often results in poor cell viability. We proposed that encapsulating cells in this hydrogel would protect cells from detrimental mechanical forces during injection and increase cell viability. The hydrogel was tested at multiple weights and carbon nanobrush concentrations to determine how gel weight affects cell viability as well as to allow the gels to remain as electrically conductive scaffolds. This work assessed the ability of the hydrogel to prevent cell membrane bursting. We used D1 multipotent mouse bone marrow stromal precursor cells for this study. We found that the pressure drop increases with increasing weight of the gels. However, cell viability also increases as the weight of the gels increases. These results support the proposition that hydrogels can be used to protect cells during syringe needle injection. Since these hydrogels undergo a reverse phase transition, the gels can be used to transplant cells into the body in solution form through injection. The gels will then harden in situ to allow for cell proliferation and tissue regeneration at the desired site.
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- 2014
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7. Incentives for organ donation: proposed standards for an internationally acceptable system.
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Matas AJ, Satel S, Munn S, Richards JR, Tan-Alora A, Ambagtsheer FJ, Asis MD, Baloloy L, Cole E, Crippin J, Cronin D, Daar AS, Eason J, Fine R, Florman S, Freeman R, Fung J, Gaertner W, Gaston R, Ghahramani N, Ghods A, Goodwin M, Gutmann T, Hakim N, Hippen B, Huilgol A, Kam I, Lamban A, Land W, Langnas A, Lesaca R, Levy G, Liquette R, Marks WH, Miller C, Ona E, Pamugas G, Paraiso A, Peters TG, Price D, Randhawa G, Reed A, Rigg K, Serrano D, Sollinger H, Sundar S, Teperman L, van Dijk G, Weimar W, and Danguilan R
- Subjects
- Humans, Motivation, Principle-Based Ethics, Tissue Donors ethics, Tissue and Organ Procurement ethics
- Abstract
Incentives for organ donation, currently prohibited in most countries, may increase donation and save lives. Discussion of incentives has focused on two areas: (1) whether or not there are ethical principles that justify the current prohibition and (2) whether incentives would do more good than harm. We herein address the second concern and propose for discussion standards and guidelines for an acceptable system of incentives for donation. We believe that if systems based on these guidelines were developed, harms would be no greater than those to today's conventional donors. Ultimately, until there are trials of incentives, the question of benefits and harms cannot be satisfactorily answered., (© 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)
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- 2012
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8. Carbon nanobrush-containing poloxamer hydrogel composites for tissue regeneration.
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Marks WH, Yang SC, Dombi GW, and Bhatia SK
- Subjects
- Electric Conductivity, Guided Tissue Regeneration methods, Humans, Wound Healing, Fibroblasts metabolism, Hydrogel, Polyethylene Glycol Dimethacrylate chemistry, Myocytes, Cardiac metabolism, Nanotubes, Carbon chemistry, Poloxamer chemistry, Tissue Engineering methods, Tissue Scaffolds
- Abstract
The objective of this study was to examine potential uses for electrically conductive hydrogel composites in tissue engineering and tissue regeneration, and to explore the composites as a growth matrix for clinically relevant cell lines. The composite was comprised of carbon nanobrushes embedded in a biocompatible poloxamer gel. In this study, we assessed the ability of such composite gels to support the growth of fibroblasts and myocytes and eventually serve as a matrix to stimulate wound closure. In such a model, fibroblasts and myocytes are seeded on the hydrogel and bathed in culture medium. The experimental model assesses the ability of fibroblasts and myocytes to grow into and adhere to the gel. The results of this study demonstrate that carbon nanobrushes can be dispersed within poloxamer gels and that fibroblasts and myocytes can proliferate within homogenously dispersed carbon nanobrush-containing poloxamer gels. We also examined the effects of carbon nanobrush content on the rheological properties of the poloxamer gel matrix; improvement occurred in several areas in the presence of carbon nanobrushes. Our future studies will investigate the effects of design parameters such as carbon nanobrush content and matrix structure on wound healing, as well as the growth of tendons and other cell lines within the hydrogel composites. In general, this work has relevance for tissue and cellular engineering and tissue regeneration in clinical medicine.
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- 2012
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9. Posttransplantation lymphoproliferative disorder in kidney and heart transplant recipients receiving thymoglobulin: a systematic review.
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Marks WH, Ilsley JN, and Dharnidharka VR
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- Humans, Antilymphocyte Serum administration & dosage, Heart Transplantation adverse effects, Kidney Transplantation adverse effects, Lymphoproliferative Disorders etiology
- Abstract
Posttransplantation lymphoproliferative disorder (PTLD) is an important complication of transplantation. Risk factors include increased overall immunosuppression exposure and inadequate antiviral prophylaxis; however, the effects of T-cell-depleting agents on PTLD are unclear. A systematic literature review was conducted to assess PTLD in clinical studies published 1999-2009 in transplant patients with ≥ 3 years follow-up who received Thymoglobulin for induction. Twenty studies were identified (12 kidney, 7 heart, and 1 liver), of which 3 were excluded for insufficient PTLD reporting. The final study group comprised 2,246 kidney and heart transplant recipients (liver study excluded) who received Thymoglobulin. At a median follow-up of 5 years, the incidence of PTLD was 0.98% (kidney, 0.93%; heart, 1.05%) among Thymoglobulin-treated patients. The cumulative Thymoglobulin dose reported in these studies was not associated with the development of PTLD (P = NS). However, incidence of PTLD was significantly lower with antiviral prophylaxis (0.63%) than without (1.87%; P = .013). Heart transplant recipients not receiving antiviral prophylaxis had the highest PTLD incidence, possibly attributable to a greater overall immunosuppressive burden. This analysis revealed that PTLD incidences in kidney and heart transplant recipients receiving Thymoglobulin were low overall and perhaps related more to concomitant anti-viral prophylaxis use., (Copyright © 2011 Elsevier Inc. All rights reserved.)
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- 2011
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10. Tripterygium wilfordii Hook F. versus Sulfasalazine in the treatment of rheumatoid arthritis: a well-designed clinical trial of a botanical demonstrating effectiveness.
- Author
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Marks WH
- Subjects
- Humans, Periodicals as Topic, Randomized Controlled Trials as Topic, Sulfasalazine therapeutic use, Treatment Outcome, Anti-Inflammatory Agents therapeutic use, Arthritis, Rheumatoid drug therapy, Drugs, Chinese Herbal therapeutic use, Phytotherapy, Tripterygium
- Abstract
Claims that Traditional/Alternative medicine (TM/AM) remedies are effective are routinely ignored by Western Medicine. However, the results of a clinical trial that demonstrated the clinical efficacy of Tripterygium wilfordii Hook F. (TW), a TM used as an anti-inflammatory, were recently published in the Annals of Internal Medicine. Why this article was published in a peer reviewed Allopathic medical journal is an important question that begs examination and may lay the future promise of TM/AM therapeutic interventions., (Copyright © 2010. Published by Elsevier B.V.)
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- 2011
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11. Immunosuppression with belatacept-based, corticosteroid-avoiding regimens in de novo kidney transplant recipients.
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Ferguson R, Grinyó J, Vincenti F, Kaufman DB, Woodle ES, Marder BA, Citterio F, Marks WH, Agarwal M, Wu D, Dong Y, and Garg P
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- Abatacept, Adrenal Cortex Hormones adverse effects, Adult, Calcineurin Inhibitors, Female, Graft Rejection, Graft Survival drug effects, Humans, Immunoconjugates adverse effects, Immunosuppression Therapy adverse effects, Kidney physiology, Kidney Transplantation, Male, Middle Aged, Mycophenolic Acid analogs & derivatives, Mycophenolic Acid therapeutic use, Sirolimus therapeutic use, Tacrolimus therapeutic use, Immunoconjugates therapeutic use, Immunosuppression Therapy methods
- Abstract
Current immunosuppressive regimens in renal transplantation typically include calcineurin inhibitors (CNIs) and corticosteroids, both of which have toxicities that can impair recipient and allograft health. This 1-year, randomized, controlled, open-label, exploratory study assessed two belatacept-based regimens compared to a tacrolimus (TAC)-based, steroid-avoiding regimen. Recipients of living and deceased donor renal allografts were randomized 1:1:1 to receive belatacept-mycophenolate mofetil (MMF), belatacept-sirolimus (SRL), or TAC-MMF. All patients received induction with 4 doses of Thymoglobulin (6 mg/kg maximum) and an associated short course of corticosteroids. Eighty-nine patients were randomized and transplanted. Acute rejection occurred in 4, 1 and 1 patient in the belatacept-MMF, belatacept-SRL and TAC-MMF groups, respectively, by Month 6; most acute rejection occurred in the first 3 months. More than two-thirds of patients in the belatacept groups remained on CNI- and steroid-free regimens at 12 months and the calculated glomerular filtration rate was 8-10 mL/min higher with either belatacept regimen than with TAC-MMF. Overall safety was comparable between groups. In conclusion, primary immunosuppression with belatacept may enable the simultaneous avoidance of both CNIs and corticosteroids in recipients of living and deceased standard criteria donor kidneys, with acceptable rates of acute rejection and improved renal function relative to a TAC-based regimen., (©2010 The Authors Journal compilation©2010 The American Society of Transplantation and the American Society of Transplant Surgeons.)
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- 2011
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12. Identification of a B cell signature associated with renal transplant tolerance in humans.
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Newell KA, Asare A, Kirk AD, Gisler TD, Bourcier K, Suthanthiran M, Burlingham WJ, Marks WH, Sanz I, Lechler RI, Hernandez-Fuentes MP, Turka LA, and Seyfert-Margolis VL
- Subjects
- Biomarkers, Gene Expression Profiling, Humans, Immunosuppression Therapy methods, Lymphocyte Activation immunology, Transplantation Tolerance immunology, B-Lymphocytes immunology, Immune Tolerance immunology, Kidney Transplantation immunology, Transplantation Tolerance genetics
- Abstract
Establishing long-term allograft acceptance without the requirement for continuous immunosuppression, a condition known as allograft tolerance, is a highly desirable therapeutic goal in solid organ transplantation. Determining which recipients would benefit from withdrawal or minimization of immunosuppression would be greatly facilitated by biomarkers predictive of tolerance. In this study, we identified the largest reported cohort to our knowledge of tolerant renal transplant recipients, as defined by stable graft function and receiving no immunosuppression for more than 1 year, and compared their gene expression profiles and peripheral blood lymphocyte subsets with those of subjects with stable graft function who are receiving immunosuppressive drugs as well as healthy controls. In addition to being associated with clinical and phenotypic parameters, renal allograft tolerance was strongly associated with a B cell signature using several assays. Tolerant subjects showed increased expression of multiple B cell differentiation genes, and a set of just 3 of these genes distinguished tolerant from nontolerant recipients in a unique test set of samples. This B cell signature was associated with upregulation of CD20 mRNA in urine sediment cells and elevated numbers of peripheral blood naive and transitional B cells in tolerant participants compared with those receiving immunosuppression. These results point to a critical role for B cells in regulating alloimmunity and provide a candidate set of genes for wider-scale screening of renal transplant recipients.
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- 2010
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13. Domino paired kidney donation: a strategy to make best use of live non-directed donation.
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Montgomery RA, Gentry SE, Marks WH, Warren DS, Hiller J, Houp J, Zachary AA, Melancon JK, Maley WR, Rabb H, Simpkins C, and Segev DL
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- Adult, Blood Group Incompatibility, Female, Humans, Male, Middle Aged, Resource Allocation methods, Tissue and Organ Procurement methods, Waiting Lists, Kidney Transplantation ethics, Living Donors ethics, Resource Allocation ethics, Tissue and Organ Procurement ethics
- Published
- 2006
- Full Text
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14. Report of a National Conference on Donation after cardiac death.
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Bernat JL, D'Alessandro AM, Port FK, Bleck TP, Heard SO, Medina J, Rosenbaum SH, Devita MA, Gaston RS, Merion RM, Barr ML, Marks WH, Nathan H, O'connor K, Rudow DL, Leichtman AB, Schwab P, Ascher NL, Metzger RA, Mc Bride V, Graham W, Wagner D, Warren J, and Delmonico FL
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- Adolescent, Adult, Child, Humans, Liver Transplantation mortality, Liver Transplantation statistics & numerical data, Middle Aged, Patient Selection, Death, Sudden, Cardiac, Tissue and Organ Procurement ethics
- Abstract
A national conference on organ donation after cardiac death (DCD) was convened to expand the practice of DCD in the continuum of quality end-of-life care. This national conference affirmed the ethical propriety of DCD as not violating the dead donor rule. Further, by new developments not previously reported, the conference resolved controversy regarding the period of circulatory cessation that determines death and allows administration of pre-recovery pharmacologic agents, it established conditions of DCD eligibility, it presented current data regarding the successful transplantation of organs from DCD, it proposed a new framework of data reporting regarding ischemic events, it made specific recommendations to agencies and organizations to remove barriers to DCD, it brought guidance regarding organ allocation and the process of informed consent and it set an action plan to address media issues. When a consensual decision is made to withdraw life support by the attending physician and patient or by the attending physician and a family member or surrogate (particularly in an intensive care unit), a routine opportunity for DCD should be available to honor the deceased donor's wishes in every donor service area (DSA) of the United States.
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- 2006
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15. Organ donation and utilization, 1995-2004: entering the collaborative era.
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Marks WH, Wagner D, Pearson TC, Orlowski JP, Nelson PW, McGowan JJ, Guidinger MK, and Burdick J
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- Ethnicity, History, 20th Century, History, 21st Century, Humans, Organ Transplantation trends, Tissue Donors, Tissue and Organ Harvesting methods, Tissue and Organ Harvesting statistics & numerical data, Tissue and Organ Procurement trends, United States, Living Donors statistics & numerical data, Organ Transplantation history, Organ Transplantation statistics & numerical data, Tissue and Organ Procurement history, Tissue and Organ Procurement statistics & numerical data
- Abstract
Continued progress in organ donation will help enable transplantation to alleviate the increasing incidence of end-stage organ disease. This article discusses the implementation and effect of the federally initiated Organ Donation Breakthrough Collaborative; it then reviews organ donation data, living and deceased, from 1995 to 2004. It is the first annual report of the Scientific Registry of Transplant Recipients to include national data following initiation of the collaborative in 2003. Prior to that, annual growth in deceased donation was 2%-4%; in 2004, after initiation of the collaborative, deceased donation increased 11%. Identification and dissemination of best practices for organ donation have emphasized new strategies for improved consent, including revised approaches to minority participation, timing of requests and team design. The number of organs recovered from donation after cardiac death (DCD) grew from 64 in 1995 to 391 in 2004. While efforts are ongoing to develop methodologies for identifying expanded criteria donors (ECD) for organs other than kidney, it is clear DCD and ECD raise questions regarding cost and recovery. The number of living donor organs increased from 3493 in 1995 to 7002 in 2004; data show trends toward more living unrelated donors and those providing non-directed donations.
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- 2006
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16. Organ donation and utilization in the United States, 2004.
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Delmonico FL, Sheehy E, Marks WH, Baliga P, McGowan JJ, and Magee JC
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- Ethnicity, Humans, Living Donors, United States, Tissue and Organ Procurement statistics & numerical data
- Abstract
This article discusses issues directly related to the organ donation process, including donor consent, donor medical suitability, non-recovery of organs, organs recovered but not transplanted, expanded criteria donors (ECD), and donation after cardiac death (DCD). The findings and topics covered have important implications for how to evaluate and share best practices of organ donation as implemented by organ procurement organizations (OPOs) and major donor hospitals in the same donation service areas (DSAs). In 2002 and 2003, US hospitals referred more than one million deaths or imminent deaths to the OPOs of their DSA. Referrals increased by nearly 10% from 2002 to 2003 (1,022,280 to 1,121,392). Donor consents have increased by about 5% and the number of total deceased donors has risen from 6,187 to 6,455. Since multiple organs are recovered from most donors, this increase allowed more than 500 additional wait-listed candidates to receive an organ transplant than in the prior year. Non-traditional donor sources have experienced a large rate of increase; in 2003 the number of ECD kidney donors increased by 8% and the number of DCD donors increased by 43%, from 189 donors in year 2002 to 271 donors in 2003.
- Published
- 2005
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17. Morbid obesity is not a contraindication to kidney transplantation.
- Author
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Marks WH, Florence LS, Chapman PH, Precht AF, and Perkinson DT
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- Actuarial Analysis, Adult, Body Mass Index, Case-Control Studies, Cause of Death, Contraindications, Female, Follow-Up Studies, Graft Rejection epidemiology, Graft Rejection etiology, Graft Survival, Humans, Kidney Failure, Chronic complications, Kidney Failure, Chronic mortality, Length of Stay statistics & numerical data, Living Donors, Male, Middle Aged, Patient Readmission statistics & numerical data, Patient Selection, Practice Guidelines as Topic, Quality of Life, Surgical Wound Infection epidemiology, Surgical Wound Infection etiology, Survival Analysis, Treatment Outcome, Washington epidemiology, Kidney Failure, Chronic surgery, Kidney Transplantation mortality, Kidney Transplantation psychology, Obesity, Morbid complications
- Abstract
Background: Concern that morbidly obese (body mass index [BMI] 35) kidney transplant recipients have worse outcomes than non-morbidly obese recipients leads many transplant centers to deny them the benefit of kidney transplantation. These concerns are supported by guidelines recently published by the American Society of Transplantation. However, successfully transplanted morbidly obese persons have a survival advantage over those that remain on dialysis. It is our practice to evaluate morbidly obese transplant candidates for transplantation under the same criteria used for nonobese candidates. This report reviews our experience with morbidly obese kidney transplant recipients having a three year follow-up., Methods: Outcomes for 23 morbidly obese (BMI 35, range 37 to 56) kidney transplant recipients transplanted between January 1995 and February 2000 were compared with 224 nonobese (BMI 25) kidney recipients transplanted during the same period., Results: Patient and graft survivals were similar between both groups. Although 3-year graft survival for morbidly obese recipients of cadaver organs was 75% compared with 90% for the nonobese group, this finding was not statistically significant, and 3-year graft survival was 100% for morbidly obese recipients of living donor organs compared with 91% for nonobese recipients. Morbidly obese recipients had significantly longer hospital stays, higher readmission rates, and a higher wound infection rate than nonobese recipients., Conclusions: We found that morbidly obese persons have 3-year graft and patient survivals similar to nonobese persons. Although they also have greater complications and greater numbers of days in the hospital, we believe these reasons are not sufficient to deny morbidly obese persons the survival and quality-of-life advantages of kidney transplantation.
- Published
- 2004
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18. Transplant tumor registry: donor related malignancies.
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Myron Kauffman H, McBride MA, Cherikh WS, Spain PC, Marks WH, and Roza AM
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- Cadaver, Humans, Living Donors, Tissue and Organ Procurement organization & administration, United States epidemiology, Neoplasms epidemiology, Postoperative Complications epidemiology, Registries, Tissue Donors
- Abstract
Background: Transmission of donor malignancies has been intermittently reported since the early days of clinical transplantation. The incidence of United States donor related malignancies has not previously been documented., Methods: All donor related malignancies reported to the Organ Procurement and Transplantation Network/United Network for Organ Sharing from 4/1/94-7/1/01 in a cohort of 34,933 cadaveric donors and 108,062 recipients were investigated by contacting the transplant centers to verify that the reported tumors were of donor origin. Time and mode of discovery, as well as graft and patient outcome, were determined. The status of other recipients from the donor was investigated., Results: A total of 21 donor related malignancies from 14 cadaveric and 3 living donors were reported. Fifteen tumors were donor transmitted and 6 were donor derived. Transmitted tumors are malignancies that existed in the donor at the time of transplantation. Derived tumors are de novo tumors that develop in transplanted donor hematogenous or lymphoid cells after transplantation. The cadaveric donor related tumor rate is 0.04% (14 of 34,993). The donor related tumor rate among transplanted cadaveric organs is 0.017% (18 of 108,062). Among patients developing donor related malignancies, the overall mortality rate was 38%, with that of transmitted tumors being 46% and derived tumors being 33%. The cadaveric donor related tumor mortality rate is 0.007% (8 of 108,062)., Conclusions: The United States incidence of donor related tumors is extremely small. The donor related tumor death rate is also extremely small, particularly when compared with waiting-list mortality.
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- 2002
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19. Elevated intestinal fatty acid binding protein and gastrointestinal complications following cardiopulmonary bypass: a preliminary analysis.
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Holmes JH 4th, Lieberman JM, Probert CB, Marks WH, Hill ME, Paull DL, Guyton SW, Sacchettini J, and Hall RA
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- Aged, Fatty Acid-Binding Protein 7, Fatty Acid-Binding Proteins, Female, Humans, Intestinal Mucosa metabolism, Intestines blood supply, Male, Middle Aged, Predictive Value of Tests, Prospective Studies, Cardiopulmonary Bypass, Carrier Proteins urine, Ischemia metabolism, Neoplasm Proteins, Postoperative Complications metabolism, Tumor Suppressor Proteins
- Abstract
Background: Cardiopulmonary bypass (CPB) is associated with poorly understood alterations in gastrointestinal (GI) perfusion. Intestinal fatty acid binding protein (IFABP), a cytosolic protein uniquely located in mature small-intestinal enterocytes, has been shown to be a sensitive biochemical marker of early intestinal ischemia when assayed in urine. We hypothesized that if significant small-intestinal ischemia occurs with CPB, then urine IFABP levels should be concomitantly elevated., Methods: Twenty-nine patients (15 low risk and 14 high risk) undergoing cardiac surgery with CPB were studied prospectively. Serial urine IFABP levels were measured and results were correlated with clinical outcomes., Results: None of the low-risk patients had IFABP elevations or experienced GI complications. Five of the high-risk patients had IFABP elevations, and three of the five developed GI complications. Within the high-risk cohort, the only significant difference between patients with or without IFABP elevations was the GI complication rate (P = 0.03). Overall, patients with IFABP elevations had a significantly higher mean ASA class and significant increases in mean CPB and aortic cross-clamp times, mean time to oral intake, median ICU and postoperative lengths of stay, and GI complications., Conclusions: In low-risk bypass patients, small-bowel mucosal perfusion appeared to be maintained, while in the high-risk population, 21% of the patients sustained clinically significant mucosal compromise. In this pilot study, urine IFABP was 100% sensitive and 92% specific with respect to GI complications. Since elevated urine IFABP concentrations appeared to correlate with clinical GI complications, urine IFABP may be a useful marker to identify the patient at risk for postbypass GI complications., (Copyright 2001 Academic Press.)
- Published
- 2001
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20. Lack of utility of intestinal fatty acid binding protein levels in predicting intestinal allograft rejection.
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Kaufman SS, Lyden ER, Marks WH, Lieberman J, Sudan DL, Fox IF, Shaw BW Jr, Horslen SP, and Langnas AN
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- Adult, Biomarkers blood, Biomarkers urine, Carrier Proteins urine, Child, Child, Preschool, Fatty Acid-Binding Protein 7, Fatty Acid-Binding Proteins, Fatty Acids metabolism, Graft Rejection blood, Graft Rejection pathology, Humans, Intestines pathology, Monitoring, Physiologic methods, Reproducibility of Results, Transplantation, Homologous pathology, Carrier Proteins blood, Graft Rejection diagnosis, Intestines transplantation, Neoplasm Proteins, Transplantation, Homologous physiology, Tumor Suppressor Proteins
- Abstract
Introduction: The enterocyte-specific protein, intestinal fatty acid binding protein (I-FABP), is detectable in serum only after intestinal injury. Previous studies in animals suggest that I-FABP might be a useful marker of intestinal allograft rejection., Materials and Methods: I-FABP was repetitively measured in nine intestinal transplant recipients and correlated with findings of surveillance endoscopy., Results: Average interval between I-FABP determination and biopsy was 3.4 days (SD=4.2 days). Average number of rejection episodes per patient totalled 1.6+/-1.2. General linear modeling demonstrated no tendency for increases in serum FABP to precede histologic graft rejection (P=0.263). Restriction of the analysis to I-FABP determinations 1 day before or on the day of biopsy failed to affect these results. Minor increases in I-FABP were often associated with histologically normal grafts, whereas rejection often occurred when I-FABP was not detectable., Discussion: Serum I-FABP levels do not predict clinical intestinal allograft rejection.
- Published
- 2001
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- View/download PDF
21. Impact of intestinal ischemia-reperfusion on cytokine profile and enterocyte viability in human syngeneic intestinal transplantation.
- Author
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Kadry Z, Roux-Lombard P, Dayer JM, Lieberman J, Marks WH, Dafoe D, Cretin N, Cighetti G, Buhler L, Charbonnet P, and Morel P
- Subjects
- Biomarkers blood, Carrier Proteins analysis, Cell Survival, Fatty Acid-Binding Protein 7, Fatty Acid-Binding Proteins, Fatty Acids metabolism, Humans, Immunoenzyme Techniques, Interleukin-6 blood, Interleukin-8 blood, Intestinal Mucosa blood supply, Intestinal Mucosa immunology, Intestines blood supply, Intestines immunology, Myelin P2 Protein analysis, Sensitivity and Specificity, Transplantation, Isogeneic pathology, Tumor Necrosis Factor-alpha analysis, Cytokines blood, Interleukins blood, Intestinal Mucosa transplantation, Intestines transplantation, Neoplasm Proteins, Reperfusion Injury immunology, Transplantation, Isogeneic immunology, Tumor Suppressor Proteins
- Published
- 2000
- Full Text
- View/download PDF
22. Total warm ischemia and reperfusion impairs flow in all rat gut layers but increases leukocyte-vessel wall interactions in the submucosa only.
- Author
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Beuk RJ, Heineman E, Tangelder GJ, Quaedackers JS, Marks WH, Lieberman JM, and oude Egbrink MG
- Subjects
- Animals, Biomarkers, Blood Flow Velocity physiology, Cell Membrane Permeability immunology, Fatty Acid-Binding Protein 7, Fatty Acid-Binding Proteins, Intestinal Mucosa immunology, Intestinal Mucosa pathology, Intestine, Small pathology, Leukocytes pathology, Male, Microcirculation pathology, Rats, Rats, Inbred Lew, Reperfusion Injury pathology, Carrier Proteins metabolism, Intestinal Mucosa blood supply, Intestine, Small blood supply, Leukocytes immunology, Myelin P2 Protein metabolism, Neoplasm Proteins, Nerve Tissue Proteins, Reperfusion Injury immunology
- Abstract
Objective: To study the effect of warm ischemia and reperfusion (I/R) on local perfusion and leukocyte-vessel wall interactions in vivo in all small bowel layers, and to quantify small bowel tissue injury histologically and by measuring intestinal fatty acid binding protein (I-FABP) release from the enterocytes., Summary Background Data: Gut injury as a result of I/R plays a pivotal role in a variety of clinical conditions, such as small bowel transplantation, heart or aortic surgery, and (septic) shock. The precise mechanism behind I/R injury and the role of microvascular changes remain unclear. The influence of warm I/R of the gut on microvascular parameters in the different gut layers has not been studied before., Methods: Anesthetized Lewis rats were either subjected to 30 minutes of ischemia and 1 hour of reperfusion or sham-treated as controls. After ligating the inferior mesenteric artery, total warm ischemia was induced by clamping the superior mesenteric artery. Intravital video microscopic measurements were obtained at intervals. Tissue injury of the small bowel and other organs was histologically evaluated afterward. In addition, plasma levels of I-FABP were determined to measure enterocyte damage., Results: After ischemia, mean red blood cell velocity decreased significantly in all layers of the small bowel, but no diameter changes were observed. Leukocyte-vessel wall interactions increased in the submucosa but not in the muscle layers. Plasma levels of I-FABP significantly increased from 30 minutes of reperfusion onward. The intestinal mucosa was severely injured; no histologic damage was detected in other tissues., Conclusions: This is the first in vivo study showing that total warm ischemia of the rat gut impairs perfusion in the whole small bowel, whereas leukocyte-vessel wall interactions increase in the submucosal layer only. Therefore, the early inflammatory response to I/R seems to be limited to the submucosa. Both microvascular effects may have contributed to the severe morphologic and functional mucosal injury observed after I/R.
- Published
- 2000
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23. Plasma intestinal fatty acid binding protein in neonates with necrotizing enterocolitis: a pilot study.
- Author
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Edelson MB, Sonnino RE, Bagwell CE, Lieberman JM, Marks WH, and Rozycki HJ
- Subjects
- Biomarkers blood, Fatty Acid-Binding Protein 7, Fatty Acid-Binding Proteins, Humans, Infant, Newborn, Pilot Projects, Sensitivity and Specificity, Severity of Illness Index, Carrier Proteins blood, Enterocolitis, Necrotizing blood, Fatty Acids blood, Intestine, Small metabolism, Myelin P2 Protein blood, Neoplasm Proteins, Tumor Suppressor Proteins
- Abstract
Background/purpose: Intestinal fatty acid-binding protein (IFABP) is found within cells at the tip of the intestinal villi, an area commonly injured when necrotizing enterocolitis (NEC) occurs. This study was undertaken to determine if measuring IFABP concentrations in the bloodstream early in the course of NEC would differentiate patients by severity before clinical findings made it clear who had stage 3 NEC and who had milder stages., Methods: Three plasma samples from newborn infants evaluated for NEC were obtained at symptom onset and after 8 and 24 hours. IFABP concentration was measured by radioimmunoassay. Infants were classified by the final and most severe stage of NEC, and IFABP levels were compared between groups at each sampling., Results: IFABP was detectable in blood samples from all 7 infants with stage 3 NEC compared with 3 of 24 with stages 1 or 2 NEC. Elevated plasma IFABP concentrations were detectable before clinical staging could be made in 5 of the 7 subjects with stage 3 NEC., Conclusion: IFABP may be a specific marker for early identification of severe NEC.
- Published
- 1999
- Full Text
- View/download PDF
24. Intestinal mucosal injury in critically ill surgical patients: preliminary observations.
- Author
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Gollin G, Zieg PM, Cohn SM, Lieberman JM, and Marks WH
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Carrier Proteins blood, Carrier Proteins urine, Critical Illness, Fatty Acid-Binding Protein 7, Fatty Acid-Binding Proteins, Fatty Acids blood, Fatty Acids urine, Female, Humans, Intestinal Mucosa metabolism, Male, Middle Aged, Myelin P2 Protein blood, Myelin P2 Protein urine, Prospective Studies, Severity of Illness Index, Systemic Inflammatory Response Syndrome blood, Systemic Inflammatory Response Syndrome urine, Intestinal Mucosa blood supply, Ischemia etiology, Neoplasm Proteins, Systemic Inflammatory Response Syndrome physiopathology, Tumor Suppressor Proteins
- Abstract
This was a prospective study designed to evaluate the extent to which intestinal mucosal compromise occurs in adult critical care patients with and without systemic inflammatory response syndrome (SIRS) and to correlate the degree of intestinal injury with outcome. Ten patients from a university hospital surgical intensive care unit were identified who manifested SIRS at the time of admission to the intensive care unit. Five other critical care patients without SIRS were also evaluated. The Acute Physiology and Chronic Health Evaluation II score was determined. Intestinal mucosal viability was assessed by serial measurement of serum and urine iFABP intestinal fatty acid binding protein (iFABP), a sensitive and specific marker for mucosal injury. Outcome in terms of the development of multiorgan dysfunction syndrome, adult respiratory distress syndrome, and survival was determined. iFABP was detectable in the serum or urine in 8 out of 10 patients with SIRS. Among the 4 patients with detectable serum iFABP, 2 died and 1 developed severe adult respiratory distress syndrome. Nine of 11 patients without detectable serum iFABP recovered without major morbidity. iFABP was detectable in most patients with SIRS, suggesting that subclinical intestinal mucosal compromise is a frequent component of this syndrome. When iFABP was detectable, particularly in the serum, the prognosis was poor, even in the absence of SIRS, indicating that iFABP may be a relevant and independent predictor of outcome in critical care patients.
- Published
- 1999
25. Human intestinal fatty acid binding protein: report of an assay with studies in normal volunteers and intestinal ischemia.
- Author
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Lieberman JM, Sacchettini J, Marks C, and Marks WH
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Animals, Antibody Specificity, Binding, Competitive physiology, Body Fluids chemistry, Carrier Proteins analysis, Carrier Proteins immunology, Fatty Acid-Binding Protein 7, Fatty Acid-Binding Proteins, Fatty Acids metabolism, Female, Humans, Immunoelectrophoresis, Intestine, Small blood supply, Intestine, Small chemistry, Iodine Radioisotopes, Male, Middle Aged, Myelin P2 Protein analysis, Myelin P2 Protein immunology, Rabbits, Radioimmunoassay, Rats, Recombinant Proteins, Carrier Proteins metabolism, Colitis, Ischemic metabolism, Intestine, Small metabolism, Myelin P2 Protein metabolism, Neoplasm Proteins, Nerve Tissue Proteins, Tumor Suppressor Proteins
- Abstract
Background: Human intestinal fatty acid binding protein (hIFABP) is a cytoplasmic protein of mature small intestinal epithelium. Work with the rat demonstrated that serum levels of IFABP correlated with early phases of intestinal mucosal injury. The aim of this study was to develop an assay for hIFABP and assess its usefulness as a marker for intestinal mucosal injury in human beings., Methods: Recombinant hIFABP (r-hIFABP) was used to produce rabbit anti-hIFABP. Specificity and avidity of binding were tested with immunoprecipitation and Scatchard analysis. r-hIFABP was labeled with 125I, and a competitive assay was developed. Urine and serum from normal volunteers and from patients with necrotizing enterocolitis (NEC), acute thromboembolic related intestinal ischemia, and systemic inflammatory response syndrome were tested for hIFABP., Results: Molecular weight was 10(-12) kd, limit of detection was 1.87 ng/ml, and no cross-reactivity occurred when tested against rat IFABP or human heart FABP. Mean levels of hIFABP (ng/ml) were controls (serum less than 1.87, urine less than 1.87), NEC (serum 14.7 ng/ml), intestinal ischemia (serum 50 ng/ml, urine 52.3 ng/ml), systemic inflammatory response syndrome (serum 5.3 ng/ml, urine 13.2 ng/ml)., Conclusions: This assay is quantitative for hIFABP in serum and urine. Results from both normal persons and those with various causes of intestinal ischemia parallel our previous findings in the rat. Preliminary findings suggest that hIFABP may serve as a diagnostic marker for early intestinal mucosal compromise and, in addition, that it should prove useful as a tool in developing rationale therapeutic regimens to treat these complex clinical problems.
- Published
- 1997
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26. Co-monitoring serum anodal trypsinogen, serum amylase, and serum creatinine accurately differentiates rejection from other causes of allograft dysfunction after simultaneous pancreas-kidney transplantation.
- Author
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Lieberman JM, Marks WH, Stuart FP, Abecassis MM, Florence LS, and Kauffman D
- Subjects
- Acute Disease, Amylases urine, Biomarkers blood, Biomarkers urine, Diagnosis, Differential, Graft Rejection blood, Humans, Kidney Transplantation immunology, Monitoring, Physiologic, Pancreas Transplantation immunology, Pancreatitis blood, Transplantation, Homologous, Amylases blood, Creatinine blood, Graft Rejection diagnosis, Kidney Transplantation physiology, Pancreas Transplantation physiology, Pancreatitis diagnosis, Postoperative Complications diagnosis, Trypsinogen blood
- Published
- 1997
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27. Reduction in the incidence of early rejection in cadaveric renal allograft recipients treated with ATGAM induction and sequential mycophenolate mofetil.
- Author
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Florence LS, Howard DR, Chapman PH, Lieberman J, Perkinson DT, and Marks WH
- Subjects
- Adolescent, Adult, Azathioprine therapeutic use, Biopsy, Cadaver, Female, Graft Rejection epidemiology, Graft Rejection pathology, Humans, Immunosuppression Therapy methods, Incidence, Kidney Transplantation pathology, Male, Mycophenolic Acid therapeutic use, Tissue Donors, Transplantation, Homologous, Antilymphocyte Serum therapeutic use, Graft Rejection prevention & control, Immunosuppressive Agents therapeutic use, Kidney Transplantation immunology, Mycophenolic Acid analogs & derivatives
- Published
- 1997
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28. Asialoglycoprotein/asialoglycoprotein receptor (AGP-AGPr) interaction is an important mechanism for the uptake of FK506 by hepatocytes.
- Author
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Marks WH, Ma Y, Yirdaw G, and Florence L
- Subjects
- Administration, Oral, Animals, Asialoglycoprotein Receptor, Carrier Proteins blood, Carrier Proteins isolation & purification, Carrier Proteins metabolism, Cells, Cultured, DNA-Binding Proteins blood, DNA-Binding Proteins isolation & purification, DNA-Binding Proteins metabolism, Flow Cytometry, Heat-Shock Proteins blood, Heat-Shock Proteins isolation & purification, Heat-Shock Proteins metabolism, Humans, Immunosuppressive Agents administration & dosage, Liver metabolism, Rats, Tacrolimus administration & dosage, Tacrolimus Binding Proteins, Tissue Distribution, Asialoglycoproteins metabolism, Immunosuppressive Agents pharmacokinetics, Liver immunology, Orosomucoid metabolism, Receptors, Cell Surface metabolism, Tacrolimus pharmacokinetics
- Abstract
Hepatic tissue concentrations of FK506 have been correlated with early acute rejection following liver transplantation. Asialoglycoproteins (AGP) reputedly bind FK506 in blood. AGP are removed from the circulation by the liver via the AGP receptor (AGPr), which resides on hepatocytes. This study was undertaken to determine if the AGP-AGPr mechanism enhances the delivery of FK506 to hepatocytes. Human orosomucoid (OM) was used as a representative AGP. asialoOM (aOM) was prepared by desialation of OM. Fresh rat hepatocytes were isolated by collagenase digestion. Tritium labeled FK506 (FK) was used to identify and quantitate FK506. Quantitation of FK in serum and culture media was by direct counting. FK in animal tissues used a method developed in our laboratory for the purpose. AGPr on resting hepatocytes was demonstrated by flow cytometry using FITC-orosomucoid and FITC-BSA controls. AGPr were enhanced by 2 g glucose/L. Two serum FK-binding fractions, 44 kD and 15 kD, were identified by gel filtration. Exogenous OM avidly bound FK and displaced FK activity from the 15 kD fraction. Serum (1%) and the 44 kD fraction enhanced the uptake of FK by hepatocytes, while serum depleted of OM-aOM by affinity chromatography was only 72.5% as effective as control serum; aOM enhanced the uptake of FK by hepatocytes to a degree similar to that of control serum but OM did not significantly affect the uptake of FK. Cold FK506 blocked the uptake and was dose dependent; cold CsA had no effect. Affinity extraction of OM from serum to which FK had previously been added removed 28.4% of FK activity. Following i.v. infusion, the kidney had the highest and liver the lowest tissue concentration of FK at 1 hr and 3 hr. In contrast, after oral administration the liver had the highest concentrations of the other tissues tested. The AGP-AGPr mechanism plays a significant role in the delivery of FK506 to hepatocytes and is likely responsible for the differences in bioavailability observed after oral and i.v. administration. Factors governing the AGP-AGPr mechanism are germane to understanding both the efficacy and toxicity of FK506 and the development optimal therapeutic strategies.
- Published
- 1997
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29. Systemic inflammatory response syndrome after human syngeneic intestinal transplantation: evidence for disruption of enterocyte barrier function.
- Author
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Kuo PC, Marks WH, Lieberman JM, Johnson DL, Alfrey EJ, and Dafoe DC
- Subjects
- Adult, Biomarkers blood, Carrier Proteins blood, Cytokines blood, Fatty Acid-Binding Protein 7, Fatty Acid-Binding Proteins, Fatty Acids, Humans, Inflammation, Intestinal Mucosa pathology, Intestinal Mucosa physiology, Intestine, Small pathology, Intestine, Small physiology, Living Donors, Male, Mesenteric Artery, Superior, Mesenteric Veins, Myelin P2 Protein blood, Neoplasm Recurrence, Local, Syndrome, Twins, Monozygotic, Fibromatosis, Aggressive surgery, Intestinal Mucosa transplantation, Intestine, Small transplantation, Neoplasm Proteins, Postoperative Complications, Retroperitoneal Neoplasms surgery, Tumor Suppressor Proteins, Vascular Neoplasms surgery
- Published
- 1996
30. Successfully treated invasive pulmonary aspergillosis associated with smoking marijuana in a renal transplant recipient.
- Author
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Marks WH, Florence L, Lieberman J, Chapman P, Howard D, Roberts P, and Perkinson D
- Subjects
- Female, Humans, Male, Middle Aged, Risk Factors, Antifungal Agents therapeutic use, Aspergillosis drug therapy, Aspergillosis etiology, Itraconazole therapeutic use, Kidney Transplantation adverse effects, Lung Diseases, Fungal drug therapy, Lung Diseases, Fungal etiology, Marijuana Smoking adverse effects
- Abstract
Invasive pulmonary aspergillosis (IPA) is often a lethal entity in transplant recipients (up to 90%). We report the successful treatment of a case of IPA in a renal transplant recipient whose only risk for exposure was habitual marijuana smoking. Although marijuana smoking has been linked to the development of IPA in patients immunosuppressed for a variety of reasons, this case is the first report involving a solid organ transplant recipient. The patient's clinical course and treatment are described and the literature is reviewed with respect to environmental and patient risk factors. In this case, IPA was associated with the patient's heavy usage of marijuana during the immediate posttransplant period. Treatment was successful and included the experimental amphotericin product amphotericin B colloidal dispersion. Contemporaneous exposure to a large amount of inocula of Aspergillus within 30 days of receiving high doses of steroids appeared to be the most important factor that predisposed this patient to IPA. Transplant recipients should be specifically proscribed from marijuana use during periods of high steroid administration.
- Published
- 1996
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31. Human syngeneic intestinal transplantation: evaluation of enterocyte viability with serum levels of intestinal fatty acid binding protein.
- Author
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Kuo PC, Morris J, Marks WH, Lieberman JM, Johnson DL, Alfrey EJ, Bastidas JA, and Dafoe DC
- Subjects
- Adult, Biomarkers blood, Cell Survival, Cytokines blood, Enteritis etiology, Epithelial Cells, Fatty Acid-Binding Protein 7, Fatty Acid-Binding Proteins, Humans, Male, Postoperative Complications, Transplantation, Isogeneic, Carrier Proteins blood, Cecum transplantation, Enteritis diagnosis, Fatty Acids metabolism, Ileum transplantation, Intestines cytology, Myelin P2 Protein blood, Neoplasm Proteins, Tumor Suppressor Proteins
- Abstract
In a case of human syngeneic intestinal transplantation, the post-operative course was complicated by the Systemic Inflammatory Response System (SIRS). This syndrome was characterized by negative cultures and elevated levels of the pro-inflammatory cytokines, IL-1 beta, IL-6 and TNF. In keeping with current concepts of translocation across the enterocyte barrier as the etiology of SIRS, levels of intestinal fatty acid binding protein (I-FABP), an enterocyte-specific protein, also increased. These observations suggest that (i) a clinical syndrome consistent with translocation may occur in the absence of rejection in intestinal transplantation, and (ii) I-FABP may serve as a clinically relevant marker for enterocyte injury.
- Published
- 1996
32. Small bowel allograft rejection detected by serum intestinal fatty acid-binding protein is reversible.
- Author
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Morrissey PE, Gollin G, and Marks WH
- Subjects
- Animals, Cyclosporine administration & dosage, Fatty Acid-Binding Protein 7, Fatty Acid-Binding Proteins, Graft Rejection pathology, Immunosuppressive Agents administration & dosage, Intestine, Small pathology, Male, Rats, Rats, Inbred BN, Rats, Inbred Lew, Time Factors, Carrier Proteins blood, Graft Rejection diagnosis, Intestine, Small transplantation, Myelin P2 Protein blood, Neoplasm Proteins, Nerve Tissue Proteins
- Abstract
We hypothesized that, following experimental small bowel transplantation, immunosuppressive therapy initiated on the day of the initial rise in serum intestinal fatty acid-binding protein (I-FABP) would result in graft salvage. In previously published work, we showed that I-FABP was not detectable in the serum of isografted Lewis rats, but could be measured in the peripheral circulation during small bowel allograft rejection. A clinically useful method to monitor trans- planted allografts for rejection should detect the problem early in its evolution so that treatment to reverse the process would salvage a functional organ. Lewis rats served as recipients of LBNF1 out-of-continuity small bowel allografts and were studied in two groups: group I (control) received no immunosuppression and group II received cyclosporine (CsA, 15 mg/kg/d, p.o.) when I-FABP rose to > or = 80 ng/ml. Serum I-FABP was measured daily until the time of sacrifice. Full-thickness graft biopsies were obtained on postoperative days 3 (baseline), 6 or 7 (elevated I-FABP), 10, and 14 (sacrifice). Following transplantation baseline serum I-FABP (day 2 or 3) averaged < or = 10.0 ng/ml. I-FABP remained at baseline through day 5 (range 0-50 ng/ml) in all animals and then rose abruptly on either day 6 or 7 (range 86-150 ng/ml; P < 0.001 vs. baseline). Histology on day 6 or 7 revealed a mild-to-moderate cellular rejection. Cyclosporine therapy reversed the rejection reaction and restored the bowel to normal histology. Serum I-FABP returned to baseline. In untreated animals, serum I-FABP remained elevated for several days and then returned to baseline levels coincident with fulminant rejection and mucosal sloughing. I-FABP was released into the peripheral circulation early in the evolution of acute rejection in this model of small bowel transplantation. Immunosuppressive therapy initiated when elevated levels of I-FABP were detected in the serum resulted in graft salvage. Cyclosporine immunotherapy consistently reversed rejection in this model. This article represents the first report of salvage of small bowel allografts when immunosuppressive therapy was instituted prospectively on the basis of a serum marker. Immunoreactive I-FABP appears to hold significant potential as a biochemical screening tool for acute rejection occurring In small bowell allografts.
- Published
- 1996
- Full Text
- View/download PDF
33. Prolongation of allograft survival in rat heterotopic heart transplantation by TLCK, a serine protease inhibitor.
- Author
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Morrissey PE, Gollin G, Brusett K, and Marks WH
- Subjects
- Animals, Cyclosporine therapeutic use, Graft Survival, Immunosuppression Therapy methods, Male, Rats, Rats, Inbred Lew, Heart Transplantation immunology, Tosyllysine Chloromethyl Ketone therapeutic use
- Published
- 1994
34. Percutaneous endoscopic gastrostomy for gastric decompression in metastatic gynecologic malignancies.
- Author
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Marks WH, Perkal MF, and Schwartz PE
- Subjects
- Adult, Aged, Female, Gastroscopy, Humans, Intestinal Obstruction etiology, Middle Aged, Carcinoma complications, Endometrial Neoplasms complications, Gastrostomy methods, Intestinal Obstruction surgery, Ovarian Neoplasms complications, Uterine Neoplasms complications
- Abstract
We report our experience with 28 patients using percutaneous endoscopic gastrostomy (PEG) for decompression of gastrointestinal obstruction as a result of carcinomatosis secondary to gynecologic malignancy. PEG could be performed successfully in 26 of the 28 patients. In two patients, intubation was not possible for technical reasons and the procedure was aborted. PEG is more cost-effective and safer than operative tube placement in these patients and offers a significantly better quality of life to the patient than does chronic nasogastric intubation.
- Published
- 1993
35. Biochemical detection of small intestinal allograft rejection by elevated circulating levels of serum intestinal fatty acid binding protein.
- Author
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Marks WH and Gollin G
- Subjects
- Animals, Fatty Acid-Binding Protein 7, Fatty Acid-Binding Proteins, Male, Rats, Rats, Inbred ACI, Rats, Inbred Lew, Transplantation, Homologous, beta-N-Acetylhexosaminidases blood, Carrier Proteins blood, Graft Rejection, Intestine, Small transplantation, Neoplasm Proteins, Nerve Tissue Proteins
- Abstract
Background: Intestinal fatty acid binding protein (I-FABP) was investigated as a serum marker for acute intestinal allograft rejection. Its behavior was compared with that of another putative marker of intestinal damage, hexosaminidase., Methods: Transplants were performed in three groups of rats: group 1, Lewis to Lewis; group 2, ACI to Lewis, no immunosuppression; and group 3, ACI to Lewis with cyclosporine given on posttransplant days 0 through 5. Daily serum I-FABP and hexosaminidase levels were quantitated and serial graft biopsy specimens were obtained., Results: Serum I-FABP levels fell to 20 ng/ml or less in all animals between posttransplant days 3 and 4. In group 1, I-FABP levels remained at baseline throughout the experiment. In group 2, I-FABP levels rose dramatically on either day 6 or 7 and declined to baseline within 4 days of the peak. On the day that I-FABP levels increased, findings of biopsy specimens were consistent with early rejection. In group 3 the rise in serum I-FABP levels was delayed 2 to 10 days. Hexosaminidase did not correlate with rejection., Conclusions: Serum I-FABP content correlated with early histologic manifestations of rejection. Hexosaminidase was insensitive as a marker in this model. I-FABP, which has a human analog, has potential as a biochemical marker for early intestinal allograft rejection.
- Published
- 1993
36. Intestinal fatty acid binding protein in serum and urine reflects early ischemic injury to the small bowel.
- Author
-
Gollin G, Marks C, and Marks WH
- Subjects
- Animals, Carrier Proteins pharmacokinetics, Fatty Acid-Binding Protein 7, Fatty Acid-Binding Proteins, Intestinal Mucosa metabolism, Kinetics, L-Lactate Dehydrogenase blood, Male, Rats, Rats, Inbred Lew, Reperfusion, beta-N-Acetylhexosaminidases blood, Carrier Proteins blood, Carrier Proteins urine, Intestine, Small blood supply, Intestines chemistry, Ischemia metabolism, Neoplasm Proteins, Nerve Tissue Proteins
- Abstract
Background: Intestinal fatty acid binding protein (I-FABP) is a 15 kd protein that constitutes 2% to 3% of enterocyte protein. Normally I-FABP is undetectable in serum. The purpose of this study was to determine whether I-FABP could be detected in peripheral serum and/or urine early in the evolution of intestinal ischemic injury., Methods: I-FABP and two putative biochemical markers of mesenteric ischemia, hexosaminidase and lactate dehydrogenase, were quantitated in the serum of rats subjected to mesenteric ischemia produced by: (1) 0.5 hours, 1 hour, or 3 hours of superior mesenteric artery (SMA) occlusion followed by reperfusion; (2) 1 hour of mesenteric occlusion to a 10 cm segment of jejunum followed by reperfusion; and (3) arterial ligation to a 10 cm segment of jejunum without reperfusion. I-FABP was also quantitated in the urine and intestinal mucosa of these animals., Results: The baseline serum I-FABP level was < or = 4.0 ng/ml in all animals. In control animals, I-FABP remained unchanged throughout the experiment. In the ischemia/reperfusion groups, I-FABP immediately appeared in the serum on reperfusion. With segmental arterial ligation, I-FABP was detected in the serum within 15 minutes. Urinary content of I-FABP rose 60 minutes after its initial appearance in the serum, and its elimination paralleled serum I-FABP levels. Serum hexosaminidase and lactate dehydrogenase levels only rose after 3 hours of SMA occlusion with reperfusion. One hour of SMA occlusion and reperfusion resulted in only mild to moderate mucosal injury, whereas 3 hours of SMA ischemia with reperfusion produced areas of transmural necrosis., Conclusions: I-FABP is released into the peripheral circulation after reversible intestinal ischemic injury and has potential as a biochemical marker to facilitate the early detection of mesenteric ischemia.
- Published
- 1993
37. Hepatic retransplantation in New England--a regional experience and survival model.
- Author
-
Powelson JA, Cosimi AB, Lewis WD, Rohrer RJ, Freeman RB, Vacanti JP, Jonas M, Lorber MI, Marks WH, and Bradley J
- Subjects
- Adolescent, Adult, Aged, Child, Child, Preschool, Humans, Infant, Liver Transplantation statistics & numerical data, Mathematics, Middle Aged, New England epidemiology, Reoperation mortality, Reoperation statistics & numerical data, Survival Rate, Liver Transplantation mortality, Models, Biological
- Abstract
Hepatic retransplantation (reTx) offers the only alternative to death for patients who have failed primary hepatic transplantation (PTx). Assuming a finite number of donor organs, reTx also denies the chance of survival for some patients awaiting PTx. The impact of reTx on overall survival (i.e., the survival of all candidates for transplantation) must therefore be clarified. Between 1983 and 1991, 651 patients from the New England Organ Bank underwent liver transplantation, and 73 reTx were performed in 71 patients (11% reTx rate). The 1-year actuarial survival for reTx (48%) was significantly less than for PTx (70%, P < 0.05). This survival varied, dependent on the interval of time following PTx in which the reTx was performed (0-3 days, 57% survival; 4-30 days, 24%; 30-365 days, 54%; and > 365 days, 83%). Patients on the regional waiting list had an 18% mortality rate while awaiting transplantation. These results were incorporated into a mathematical model describing survival as a function of reTx rate, assuming a limited supply of donor livers. ReTx improves the 1-year survival rate for patients undergoing PTx but decreases overall survival (survival of all candidates) for liver transplantation. In the current era of persistently insufficient donor numbers, strategies based on minimizing the use of reTx, especially in the case of patients in whom chances of success are minimal, will result in the best overall rate of patient survival.
- Published
- 1993
- Full Text
- View/download PDF
38. Elevation of circulating intestinal fatty acid binding protein in a luminal contents-initiated model of NEC.
- Author
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Gollin G and Marks WH
- Subjects
- Animals, Biomarkers blood, Calcium Gluconate, Caseins, Enterocolitis, Pseudomembranous pathology, Fatty Acid-Binding Protein 7, Fatty Acid-Binding Proteins, Humans, Infant, Newborn, Male, Models, Biological, Rats, Rats, Inbred Lew, Carrier Proteins blood, Enterocolitis, Pseudomembranous blood, Fatty Acids blood, Neoplasm Proteins, Nerve Tissue Proteins, Tumor Suppressor Proteins
- Abstract
Necrotizing enterocolitis (NEC) continues to produce significant morbidity and mortality, due in part to the difficulty in detecting its initial manifestations at a stage when compromised intestine may potentially be salvaged. We have previously reported our findings that intestinal fatty acid binding protein (I-FABP) is a sensitive biochemical marker for early intestinal mucosal injury due to mesenteric ischemia. In this study we evaluated the potential of serum I-FABP as a marker for incipient NEC in a nonischemic model of NEC in the rat. Intraluminal instillation of a solution of casein (10 mg/mL) and calcium gluconate (50 mg/mL) in saline acidified to pH 4.0 with propionic acid resulted in a rapid and prolonged increase in serum I-FABP from a baseline of < or = 4.0 ng/mL to 171 +/- 40 ng/mL. Instillation of the same electrolyte solution with either casein or propionic acid alone resulted in a less dramatic elevation of serum I-FABP to 19 +/- 4 ng/mL and 76 +/- 30 ng/mL, respectively. In both cases baseline values of < or = 4.0 ng/mL were reached within 60 minutes. In control animals, which received saline alone, serum I-FABP was undetectable throughout the experiment. Simultaneously, we found that serum hexosaminidase, a putative biochemical marker for intestinal ischemia and NEC, was unchanged in all groups. Light microscopy of the intestinal specimens obtained three hours after instillation of casein and organic acid demonstrated superficial villus necrosis and villus blunting, but no areas of transmural necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1993
- Full Text
- View/download PDF
39. Are calcium channel blockers protective against first-dose reactions to OKT3?
- Author
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Richard EA, Lorber MI, Marks WH, and Bia MJ
- Subjects
- Adult, Female, Humans, Lymphocyte Activation drug effects, Male, Calcium Channel Blockers therapeutic use, Muromonab-CD3 adverse effects
- Published
- 1992
40. The effect of cyclosporine administration on the cellular distribution and content of cyclophilin.
- Author
-
McDonald ML, Ardito T, Marks WH, Kashgarian M, and Lorber MI
- Subjects
- Animals, Female, Immunohistochemistry, Liver chemistry, Liver cytology, Microscopy, Fluorescence, Microscopy, Immunoelectron, Peptidylprolyl Isomerase, Rats, Rats, Inbred Strains, Tissue Distribution, Amino Acid Isomerases blood, Carrier Proteins blood, Cyclosporine administration & dosage, Lymphocytes chemistry
- Abstract
Cyclophilin (CYP), an intracellular protein sharing amino acid sequence identity with the enzyme peptidyl-prolyl cis-trans isomerase has become the leading candidate for the receptor responsible for cyclosporine biological effects. Avid binding of CYP to cyclosporine and immunosuppressive cyclosporine metabolites has been demonstrated, while nonimmunosuppressive cyclosporine metabolites have tended not to bind to cyclophilin. A previous immunohistochemical analysis documented that CYP localized principally to the cytoplasmic cellular compartment, but nuclear staining was observed among some cells. This study was undertaken to more precisely define the ultrastructural distribution of CYP, and to determine whether CYP cellular content was affected by CsA therapy. Untreated Wistar rats or those receiving 7 days of CsA (15 mg/kg/day, i.p.) were anesthetized, perfusion-fixed in situ, and sacrificed. Analyses of lymph node, spleen, thymus, kidney, liver, heart, brain, and ileum used an affinity purified, rabbit anticyclophilin IgG. Transmission electron microscopy was performed after staining with anti-CYP using a horseradish peroxidase/biotin/avidin technique. Quantitative immunofluorescence was measured by confocal microscopy using anti-CYP, with a biotin/avidin/phycoerythrin technique. Cyclophilin localized to the cytoplasmic compartment--however, association with mitochondria endoplasmic reticulum, Golgi, and with the nuclear membrane among lymphocytes, as well as cells from kidney, liver and ileum--was documented. Cyclophilin was not identified within the nucleus proper. Tissues obtained from animals receiving CsA exhibited a generalized increase in CYP content compared with tissues from untreated controls, suggesting the possibility that CsA may exert a regulatory influence upon CYP gene activation. Collectively, the data were consistent with the hypothesis that CYP exerts a central role in cellular metabolism, and that CsA-mediated biologic effects result from the CsA/CYP interaction.
- Published
- 1992
- Full Text
- View/download PDF
41. A three-year experience with serum anodal trypsinogen as a biochemical marker for rejection in pancreatic allografts. False positives, tissue biopsy, comparison with other markers, and diagnostic strategies.
- Author
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Perkal M, Marks C, Lorber MI, and Marks WH
- Subjects
- Algorithms, Amylases urine, Atrophy, Biopsy, Diagnosis, Computer-Assisted, Duodenum pathology, Duodenum transplantation, False Positive Reactions, Humans, Intestinal Mucosa pathology, Kidney pathology, Kidney Transplantation immunology, Pancreas pathology, Biomarkers blood, Graft Rejection physiology, Pancreas Transplantation immunology, Trypsinogen blood
- Abstract
Serum values of immunoreactive anodal trypsinogen (sAT) have been claimed to correlate well with rejection occurring in pancreatic allografts. We have studied the behavior of sAT in serial serum samples obtained from 39 type I diabetics undergoing whole-organ pancreas transplantation during the past 3 years. Patients had either received a pancreatic allograft simultaneously with a transplanted kidney (SPK, n = 33) or after a previous kidney transplant (pancreas after kidney [PAK] n = 6). The behavior of sAT was studied in relation to the clinical diagnosis of rejection. Graft amylase output for all 39 patients and serum creatinine for the 33 SPK recipients were also studied. Tissue biopsies were obtained from 11 patients with elevated sAT values and a presumptive diagnosis of rejection. Nine of these patients had SPK grafts and simultaneously elevated creatinine values. Tissue was obtained from the simultaneously transplanted kidney; all specimens revealed rejection. Two of the 11 patients had PAK allografts. Biopsies performed on the graft duodenum were consistent with acute rejection. Three additional patients with unchanged sAT values had biopsies for other reasons; these biopsies failed to demonstrate signs of acute rejection. Thus graft biopsy correlated exactly with sAT behavior in every case in which rejection was suspected. Five patients had elevations of sAT not associated with rejection: one resulted from direct trauma, two had outlet obstruction, and two had clinical diagnoses of graft pancreatitis. The sAT was more sensitive and specific than GAO and as sensitive as creatinine for SPK recipients. These studies confirm that sAT is a reliable, graft-specific biochemical marker for the early diagnosis of pancreatic rejection. The use of sAT should allow for the proper timing of graft biopsies and the judicious use of immunosuppressive agents, which will result in increased allograft survival for PAK and pancreas-alone allografts.
- Published
- 1992
- Full Text
- View/download PDF
42. Ultrasound imaging of pancreatico-duodenal transplants.
- Author
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Milner LN, Ramos IM, Marks WH, and Taylor KJ
- Subjects
- Cadaver, Diabetes Mellitus, Type 1 surgery, Graft Rejection, Humans, Pancreatitis diagnostic imaging, Pancreatitis etiology, Trypsinogen blood, Ultrasonics, Ultrasonography methods, Duodenum transplantation, Pancreas Transplantation diagnostic imaging, Postoperative Complications diagnostic imaging
- Abstract
A preliminary investigation of the role of ultrasound, including color and duplex Doppler, was performed in recipients of cadaveric pancreatico-duodenal transplants. Twenty such examinations were done on three patients. Three different complications were noted: rejection, pancreatitis, and peripancreatic abscess. The mean normal resistive index (RI) was 0.71 +/- 0.12. The normal allograft anteroposterior (AP) dimension ranged from 1.5 to 2.0 cm. Intraparenchymal and main feeding vessels were demonstrated easily. RI calculations alone were not helpful in diagnosing graft rejection. However, this diagnosis can be made using a new biochemical marker, serum anodal trypsinogen. We conclude that when used in conjunction with a reliable biochemical marker for rejection (serum anodal trypsinogen), ultrasound, including color and duplex Doppler, provides an important adjunct for the rapid, inexpensive, and complete evaluation of patients with pancreatico-duodenal transplants.
- Published
- 1991
- Full Text
- View/download PDF
43. The immunochemical distribution of cyclophilin in normal mammalian tissues.
- Author
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Marks WH, Harding MW, Handschumacher R, Marks C, and Lorber MI
- Subjects
- Amino Acid Isomerases metabolism, Animals, Carrier Proteins metabolism, Cyclosporins metabolism, Immunohistochemistry, Peptidylprolyl Isomerase, Protein Binding, Swine, Tissue Distribution, Amino Acid Isomerases pharmacokinetics, Carrier Proteins pharmacokinetics
- Abstract
Cyclophilin, a 17 Kd proline cis-trans isomerase, high-affinity (Kd 10(-8) M) target for the immunosuppressive drug cyclosporine has ubiquitous phylogenic distribution, but its tissue localization in mammals has not been detailed. To explore a potential relationship between the multiple systemic effects of CsA and the cellular and tissue distribution of CYP, thirty-three different normal porcine tissues were examined using an immunohistochemical technique. Tissue was obtained from farmbred pigs, immediately fixed in buffered formalin, and prepared as embedded 5-mu sections. Immune-specific staining was accomplished using an ABC immunoperoxidase method and an affinity-purified, monospecific, rabbit anti-CYP IgG. Cut sections served as their own blanks and controls, and all tissues were stained in batch to minimize the effects of variation in technique. Consistent with earlier reports, CYP was present in all tissues studied, however, there was remarkable heterogeneity in CYP distribution. Renal parenchymal cells, cardiac and striated muscle, pulmonary and skin demonstrated cytoplasmic immunospecific CYP--however, the cellular localization varied. Cytoplasmic staining of endothelial, neural, and glandular elements was consistently observed. Contrasting with previous reports, CYP localized to the nucleus as well as the cytoplasm of some lymphoid cells, hepatocytes, and cells of the large intestine. Generally, greater CYP-specific staining was noted in organs amenable to CsA immunosuppression (heart, liver, kidney), compared with organs deemed more immunologically vulnerable when allografted under CsA (pancreas, lung, small bowel). Similarly, CYP-immunospecific staining was abundant in tissues susceptible to CsA toxicities (neural tissue, smooth muscle, kidney, liver). This detailed immunohistological examination affords a correlation between CYP content and sensitivity to CsA. It also raises some new questions about tissues with little extractable CYP but significant histological staining.
- Published
- 1991
- Full Text
- View/download PDF
44. A comparison of in vivo responses to cyclosporine, FK506, and rapamycin following allogeneic immune challenge.
- Author
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Lorber MI, Wilson JH, Harding MW, Gromkowski S, and Marks WH
- Subjects
- Animals, Cyclosporins pharmacology, Interleukin-2 pharmacology, Lymphocyte Activation drug effects, Mice, Mice, Inbred C57BL, Sirolimus, Tacrolimus, Transplantation, Homologous immunology, Transplantation, Isogeneic immunology, Anti-Bacterial Agents pharmacology, Immune Tolerance drug effects, Immunosuppression Therapy methods, Immunosuppressive Agents pharmacology, Polyenes pharmacology
- Published
- 1991
- Full Text
- View/download PDF
45. Decreased tissue inhibitor of metalloproteinases (TIMP) in abdominal aortic aneurysm tissue: a preliminary report.
- Author
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Brophy CM, Marks WH, Reilly JM, and Tilson MD
- Subjects
- Aorta, Abdominal metabolism, Blotting, Western, Densitometry, Humans, Immunoelectrophoresis, Metalloendopeptidases antagonists & inhibitors, Radioimmunoassay, Tissue Inhibitor of Metalloproteinases, Aortic Aneurysm metabolism, Glycoproteins metabolism
- Abstract
Important concepts underlying the pathophysiology of abdominal aortic aneurysm (AAA) disease include a genetic predisposition, male predominance, and increased proteolysis. Proteolytic activity is carefully controlled by an abundance of protease inhibitors and the increased proteolysis may reflect a decrease in inhibitory activity. The recent assignment for the major tissue inhibitor of metalloproteinases (TIMP) to the X chromosome provides a potential link between the male predominance and increased proteolysis noted in AAA. The purpose of this investigation was to measure the amount of TIMP in normal and diseased aorta. A polyclonal antibody to recombinant human TIMP was produced in rabbit and used to establish an immunoassay. Immunoreactive TIMP in normal and diseased aorta was then measured. There was more TIMP in the matrix-associated fraction than in the soluble fraction. There was significantly less immunoreactive TIMP in aortic extracts from AAA than from control as measured both by Western blot and radioimmunoassay. These results suggest that a diminished amount of TIMP in the aortic matrix in AAA patients may contribute to the increased proteolysis observed in AAA.
- Published
- 1991
- Full Text
- View/download PDF
46. Serum markers for pancreas rejection: long-term behavior following clinical pancreatico-duodenal transplantation.
- Author
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Marks WH, Borgström A, Marks CR, Sollinger H, and Lorber MI
- Subjects
- Graft Rejection, Humans, Pancreas Transplantation physiology, Prospective Studies, Trypsin Inhibitors blood, Trypsinogen blood, Duodenum transplantation, Pancreas Transplantation immunology
- Published
- 1991
47. Cyclophilin binding: a more accurate measure of cyclosporine immunosuppressive activity after renal transplantation.
- Author
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Paul K, Harding MW, Marks WH, Handschumacher RE, and Lorber MI
- Subjects
- Chromatography, High Pressure Liquid, Cyclosporins blood, Humans, Immunosuppression Therapy, Peptidylprolyl Isomerase, Amino Acid Isomerases metabolism, Carrier Proteins metabolism, Cyclosporins metabolism, Kidney Transplantation physiology
- Published
- 1991
48. Use of Doppler imaging for evaluation of dysfunction in renal allografts.
- Author
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Taylor KJ and Marks WH
- Subjects
- Animals, Humans, Graft Rejection, Kidney Transplantation pathology, Ultrasonography
- Published
- 1990
- Full Text
- View/download PDF
49. Cyclophilin binding: a receptor-mediated approach to monitoring cyclosporine immunosuppressive activity following organ transplantation.
- Author
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Lorber MI, Paul K, Harding MW, Handschumacher RE, and Marks WH
- Subjects
- Administration, Oral, Bile metabolism, Cadaver, Cyclosporins administration & dosage, Cyclosporins adverse effects, Dose-Response Relationship, Drug, Drug Therapy, Combination, Humans, Immune Tolerance drug effects, Infusions, Intravenous, Kidney drug effects, Kidney Function Tests, Liver drug effects, Liver Function Tests, Methylprednisolone administration & dosage, Peptidylprolyl Isomerase, Prednisone administration & dosage, Structure-Activity Relationship, Carrier Proteins blood, Cyclosporins pharmacokinetics, Graft Rejection drug effects, Kidney Transplantation immunology
- Published
- 1990
50. Serum anodal trypsinogen is a predictive biochemical marker for pancreas allograft rejection.
- Author
-
Marks WH, Borgstrom A, Sollinger H, Marks C, and Lorber MI
- Subjects
- Creatine blood, Humans, Kidney Transplantation, Transplantation, Homologous, Biomarkers blood, Graft Rejection, Pancreas Transplantation, Trypsinogen blood
- Published
- 1990
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