Browsing by Subject "Transplants"

Now showing 1 - 7 of 7
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    A brief history of clinical xenotransplantation
    (Elsevier, 2015-11) Cooper, David K. C.; Ekser, Burcin; Tector, A. Joseph; Department of Surgery, IU School of Medicine
    Between the 17th and 20th centuries, blood was transfused from various animal species into patients with a variety of pathological conditions. Skin grafts were carried out in the 19th century, with grafts from a variety of animals, with frogs being the most popular. In the 1920s, Voronoff advocated the transplantation of slices of chimpanzee testis into elderly men, believing that the hormones produced by the testis would rejuvenate his patients. In 1963-4, when human organs were not available and dialysis was not yet in use, Reemtsma transplanted chimpanzee kidneys into 13 patients, one of whom returned to work for almost 9 months before suddenly dying from what was believed to be an electrolyte disturbance. The first heart transplant in a human ever performed was by Hardy in 1964, using a chimpanzee heart, but the patient died within 2 h. Starzl carried out the first chimpanzee-to-human liver transplantation in 1966; in 1992 he obtained patient survival for 70 days following a baboon liver transplant. The first clinical pig islet transplant was carried out by Groth in 1993. Today, genetically-modified pigs offer hope of a limitless supply of organs and cells for those in need of a transplant.
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    Buccal mucosal graft urethroplasty in the treatment of urethral strictures: experience using the two-surgeon technique
    (Hindawi Publishing Corporation, 2010-01-08) Arlen, Angela M.; Powell, Charles R.; Hoffman, Henry T.; Kreder, Karl J.; Urology, School of Medicine
    At our institution, the majority of buccal mucosal graft urethroplasties are performed using a two-team approach with an otolaryngologic surgeon. We report our two-surgeon experience with buccal mucosal grafting for reconstruction of all anterior urethral strictures. Twenty-four men underwent autologous buccal mucosal graft urethroplasty between October 2001 and September 2008 for recurrent urethral stricture disease. Twenty-two underwent a single-stage repair and two underwent a two-stage repair. Medical charts were retrospectively reviewed for demographics, comorbidities, etiology, location and length of stricture, and prior interventions in order to identify predictors of buccal urethroplasty success, defined as no evidence of stricture recurrence. All patients underwent retrograde urethrogram and cystoscopy. Operative and anesthesia times were evaluated. We determined an overall success rate of 83.3% (20 of 24 cases). Mean anesthesia time for single-stage urethroplasty was 155 min and mean operative time was 123 min. One of the two two-stage urethroplasties experienced stricture recurrence (50%). The single-stage buccal graft success rate was 86.4% (19 of 22 cases). Two of the four who developed recurrent stricture disease that required intervention had undergone a previous mesh urethroplasty. Complications developed in four of 24 patients (16.6%), including superficial wound infection (one), superficial wound dehiscence (two), and abscess/fistula formation requiring reoperation (one). The buccal mucosa is an ideal tissue for both single- and two-stage substitution urethroplasty for patients with recurrent stricture disease. Our two-surgeon technique minimizes anesthesia and operative times, and contributes to the overall high success rate and relatively low complication rate.
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    Challenges of the Pioneer Renal Transplants at Moi Teaching and Referral Hospital, Eldoret, Kenya
    (Association of Kenya Physicians, 2007) Ganda, B. K.; Association of Kenya Physicians Scientific Conference (11th : Mar. 2007 : Eldoret, Kenya)
    History I –Theatre: • Eldoret Dist Hosp built in 1926 • 1926-1999. One operation table • 2000-Majaliwa Theatre 4 tables; intensive care room as ICU Indiana Community • 2007-2 More operation tables. Indiana Comm.
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    Combining Theoretical and Experimental Techniques to Study Murine Heart Transplant Rejection
    (Frontiers Media SA, 2016) Arciero, Julia C.; Maturo, Andrew; Arun, Anirudh; Oh, Byoung Chol; Brandacher, Gerald; Raimondi, Giorgio; Department of Mathematical Sciences, School of Science
    The quality of life of organ transplant recipients is compromised by complications associated with life-long immunosuppression, such as hypertension, diabetes, opportunistic infections, and cancer. Moreover, the absence of established tolerance to the transplanted tissues causes limited long-term graft survival rates. Thus, there is a great medical need to understand the complex immune system interactions that lead to transplant rejection so that novel and effective strategies of intervention that redirect the system toward transplant acceptance (while preserving overall immune competence) can be identified. This study implements a systems biology approach in which an experimentally based mathematical model is used to predict how alterations in the immune response influence the rejection of mouse heart transplants. Five stages of conventional mouse heart transplantation are modeled using a system of 13 ordinary differential equations that tracks populations of both innate and adaptive immunity as well as proxies for pro- and anti-inflammatory factors within the graft and a representative draining lymph node. The model correctly reproduces known experimental outcomes, such as indefinite survival of the graft in the absence of CD4(+) T cells and quick rejection in the absence of CD8(+) T cells. The model predicts that decreasing the translocation rate of effector cells from the lymph node to the graft delays transplant rejection. Increasing the starting number of quiescent regulatory T cells in the model yields a significant but somewhat limited protective effect on graft survival. Surprisingly, the model shows that a delayed appearance of alloreactive T cells has an impact on graft survival that does not correlate linearly with the time delay. This computational model represents one of the first comprehensive approaches toward simulating the many interacting components of the immune system. Despite some limitations, the model provides important suggestions of experimental investigations that could improve the understanding of rejection. Overall, the systems biology approach used here is a first step in predicting treatments and interventions that can induce transplant tolerance while preserving the capacity of the immune system to protect against legitimate pathogens.
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    Immunobiological barriers to xenotransplantation
    (Elsevier, 2015-11) Cooper, David K. C.; Ekser, Burcin; Tector, A. Joseph; Department of Surgery, IU School of Medicine
    Binding of natural anti-pig antibodies in humans and nonhuman primates to carbohydrate antigens expressed on the transplanted pig organ, the most important of which is galactose-α1,3-galactose (Gal), activate the complement cascade, which results in destruction of the graft within minutes or hours, known as hyperacute rejection. Even if antibody is removed from the recipient's blood by plasmapheresis, recovery of antibody is associated with acute humoral xenograft rejection. If immunosuppressive therapy is inadequate, the development of high levels of T cell-dependent elicited anti-pig IgG similarly results in graft destruction, though classical acute cellular rejection is rarely seen. Vascular endothelial activation by low levels of anti-nonGal antibody, coupled with dysregulation of the coagulation-anticoagulation systems between pigs and primates, leads to a thrombotic microangiopathy in the graft that may be associated with a consumptive coagulopathy in the recipient. The most successful approach to overcoming these barriers is by genetically-engineering the pig to provide it with resistance to the human humoral and cellular immune responses and to correct the coagulation discrepancies between the two species. Organs and cells from pigs that (i) do not express the important Gal antigen, (ii) express a human complement-regulatory protein, and (iii) express a human coagulation-regulatory protein, when combined with an effective immunosuppressive regimen, have been associated with prolonged pig graft survival in nonhuman primates.
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    The need for xenotransplantation as a source of organs and cells for clinical transplantation
    (Elsevier, 2015-11) Ekser, Burcin; Cooper, David K. C.; Tector, A. Joseph; Department of Surgery, IU School of Medicine
    The limited availability of deceased human organs and cells for the purposes of clinical transplantation remains critical worldwide. Despite the increasing utilization of 'high-risk', 'marginal', or 'extended criteria' deceased donors, in the U.S. each day 30 patients either die or are removed from the waiting list because they become too sick to undergo organ transplantation. In certain other countries, where there is cultural resistance to deceased donation, e.g., Japan, the increased utilization of living donors, e.g., of a single kidney or partial liver, only very partially addresses the organ shortage. For transplants of tissues and cells, e.g., pancreatic islet transplantation for patients with diabetes, and corneal transplantation for patients with corneal blindness (whose numbers worldwide are potentially in the millions), allotransplantation will never prove a sufficient source. There is an urgent need for an alternative source of organs and cells. The pig could prove to be a satisfactory source, and clinical xenotransplantation using pig organs or cells, particularly with the advantages provided by genetic engineering to provide resistance to the human immune response, may resolve the organ shortage. The physiologic compatibilities and incompatibilities of the pig and the human are briefly reviewed.
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    Outcome with lenalidomide plus dexamethasone followed by early autologous stem cell transplantation in patients with newly diagnosed multiple myeloma on the ECOG-ACRIN E4A03 randomized clinical trial: long-term follow-up
    (Nature, 2016-09) Biran, N.; Jacobus, S.; Vesole, D. H.; Callander, N. S.; Fonseca, R.; Williams, M. E.; Abonour, R.; Katz, M. S.; Rajkumar, S. V.; Greipp, P. R.; Siegel, D. S.; Department of Medicine, IU School of Medicine
    In Eastern Cooperative Oncology Group-ACRIN E4A03, on completion of four cycles of therapy, newly diagnosed multiple myeloma patients had the option of proceeding to autologous peripheral blood stem cell transplant (ASCT) or continuing on their assigned therapy lenalidomide plus low-dose dexamethasone (Ld) or lenalidomide plus high-dose dexamethasone (LD). This landmark analysis compared the outcome of 431 patients surviving their first four cycles of therapy pursuing early ASCT to those continuing on their assigned therapy. Survival distributions were estimated using the Kaplan–Meier method and compared with log-rank test. Ninety patients (21%) opted for early ASCT. The 1-, 2-, 3-, 4- and