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1.
Ann Surg ; 267(5): 983-988, 2018 05.
Article in English | MEDLINE | ID: mdl-28509699

ABSTRACT

OBJECTIVE: We describe the first successful penis transplant in the United States in a patient with a history of subtotal penectomy for penile cancer. BACKGROUND: Penis transplantation represents a new paradigm in restoring anatomic appearance, urine conduit, and sexual function after genitourinary tissue loss. To date, only 2 penis transplants have been performed worldwide. METHODS: After institutional review board approval, extensive medical, surgical, and radiological evaluations of the patient were performed. His candidacy was reviewed by a multidisciplinary team of surgeons, physicians, psychiatrists, social workers, and nurse coordinators. After appropriate donor identification and recipient induction with antithymocyte globulin, allograft procurement and recipient preparation took place concurrently. Anastomoses of the urethra, corpora, cavernosal and dorsal arteries, dorsal vein, and dorsal nerves were performed, and also inclusion of a donor skin pedicle as the composite allograft. Maintenance immunosuppression consisted of mycophenolate mofetil, tacrolimus, and methylprednisolone. RESULTS: Intraoperative, the allograft had excellent capillary refill and strong Doppler signals after revascularization. Operative reinterventions on postoperative days (PODs) 2 and 13 were required for hematoma evacuation and skin eschar debridement. At 3 weeks, no anastomotic leaks were detected on urethrogram, and the catheter was removed. Steroid resistant-rejection developed on POD 28 (Banff I), progressed by POD 32 (Banff III), and required a repeat course of methylprednisolone and antithymocyte globulin. At 7 months, the patient has recovered partial sensation of the penile shaft and has spontaneous penile tumescence. Our patient reports increased overall health satisfaction, dramatic improvement of self-image, and optimism for the future. CONCLUSIONS: We have shown that it is feasible to perform penile transplantation with excellent results. Furthermore, this experience demonstrates that penile transplantation can be successfully performed with conventional immunosuppression. We propose that our successful penile transplantation pilot experience represents a proof of concept for an evolution in reconstructive transplantation.


Subject(s)
Penile Neoplasms/surgery , Penile Transplantation , Plastic Surgery Procedures/methods , Quality of Life , Urologic Surgical Procedures, Male/methods , Vascularized Composite Allotransplantation/methods , Adult , Computed Tomography Angiography , Follow-Up Studies , Humans , Male , Penile Neoplasms/diagnosis , Pilot Projects , Transplantation, Homologous , Treatment Outcome , Ultrasonography, Doppler
2.
Curr Opin Organ Transplant ; 22(5): 484-489, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28737527

ABSTRACT

PURPOSE OF REVIEW: Genitourinary vascularized allotransplantation (GUVCA) is gaining interest as a treatment option for patients with functional and aesthetic urogenital tissue loss. Only three cases have been done worldwide and research on the implementation and feasibility of this procedure is in an elementary state. RECENT FINDINGS: The psychosocial impact and ethical considerations with GUVCA are remote, particularly because of the intimate and personal nature of genital tissue. Though two of the three penile transplantation cases are considered successful, various unexpected factors and complications have been described alongside these successes. Treatment outcome depends on a complex combination of immunological, technical, and psychosocial components that will be different per individual case. Multidisciplinary evaluation and treatment protocols should be established to ensure that the quality of life in GUVCA recipients can be increased in a safe and ethical way. SUMMARY: Penile transplantation represents challenging new potential to improve phallus reconstruction in patients with severe genital tissue defects, but worldwide experience with GUVCA is limited. Controlled multicenter research is required to better define the risk/benefit ratio of this experimental yet promising treatment option.


Subject(s)
Quality of Life/psychology , Urogenital System/surgery , Vascularized Composite Allotransplantation/methods , Humans , Treatment Outcome
3.
Liver Transpl ; 21(2): 145-50, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25370903

ABSTRACT

Improved outcomes of liver transplantation have led to increases in the numbers of US transplant centers and candidates on the list. The resultant and ever-expanding organ shortage has created competition among centers, especially in regions with multiple liver transplant programs. Multiple reports now document that competition among the country's transplant centers has led to the listing of increasingly high-risk patients and the utilization of more marginal liver allografts. The transplant and medical communities at large should carefully re-evaluate these practices and promote innovative approaches to restoring trust in the allocation of donor organs and confirming that there is nationwide conformity in the guidelines used for evaluating and listing potential candidates for this scarce resource.


Subject(s)
Liver Transplantation , Tissue and Organ Procurement/methods , Decision Making , End Stage Liver Disease/surgery , Geography , Humans , Liver Transplantation/economics , Outcome Assessment, Health Care , Resource Allocation , Tissue Donors/supply & distribution , Treatment Outcome , United States , Waiting Lists
4.
Prog Transplant ; 24(3): 298-301, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25193733

ABSTRACT

Organ shortage is unquestionably the greatest challenge facing the field of transplantation today. Transplant centers are constantly competing with one another for limited numbers of organs for their recipients. Recruitment of specialized transplant surgical expertise and leadership is thought to enable a center to grow in volume and thus profitability in the increasingly difficult world of health care reimbursement. In this study, the pattern of kidney transplants at 13 different centers in the United Network for Organ Sharing's region 1 is examined: the comparison is between transplant volume before and after changes in the centers' leadership between 2000 and 2011. Each center's kidney transplant volume showed a significant increase after a leadership change that ultimately regressed to the center's baseline. This study is the first to show that behavioral changes in transplant center competition cause transient increases in transplant volume that quickly regress back to mean levels.


Subject(s)
Kidney Transplantation/statistics & numerical data , Leadership , Personnel Turnover , Tissue Donors/statistics & numerical data , Humans , Kidney Transplantation/economics , Personnel Turnover/economics , United States
5.
J Surg Res ; 181(1): 156-9, 2013 May 01.
Article in English | MEDLINE | ID: mdl-22683078

ABSTRACT

PURPOSE: Ureteroneocystostomy (UCN) is the most widely used urinary reconstruction technique during kidney transplantation. Disadvantages of this technique include a high incidence of hematuria and reflux, plus the potential for obstruction resulting from distal ureteral fibrosis. Pyeloureterostomy (PU) avoids these complications but increases the technical complexity. METHODS: Between January 1990 and December 2005, 1066 adults patients underwent kidney transplantations; 768 patients (72.1%) had urinary reconstruction by PU and 298 (27.9%) underwent UNC. RESULTS: Patients in the PU group underwent simultaneous ipsilateral native nephrectomy. The operative time was longer in the PU group compared with the UNC group: 210 ± 36 min versus 182 ± 24 min (P < 0.001). Overall surgical complications in the PU group were comparable to those in the UNC group (9.5% versus 12.3%). The urinary complication rate was also comparable in both groups: 3.2% (25 of 768) in the PU group and 5% (15 of 298) in the UNC group. However, urinary obstruction comprised 60% of urinary complications in the UNC group, compared with 32% in the PU group (P < 0.01). We treated most urinary complications non-operatively. However, 24% of patients (six of 25) in the PU group needed operative intervention or revision for ureteral reconstruction, compared with 46.6% (seven of 15) in the UNC group (P < 0.01). CONCLUSIONS: Pyeloureterostomy is a safe and effective method for urinary tract reconstruction in renal transplantation. Pyeloureterostomy should be part of every transplant surgeon's armamentarium.


Subject(s)
Cystostomy/methods , Kidney Transplantation/methods , Ureter/surgery , Ureterostomy/methods , Adult , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies
6.
Clin Transplant ; 27(1): 162-7, 2013.
Article in English | MEDLINE | ID: mdl-23004927

ABSTRACT

INTRODUCTION: For most cancers, a two- to five-yr period with no evidence of disease must be demonstrated before organ transplantation. The natural history of prostate cancer is unique both because of extensive pre-treatment screening and the ease of post-treatment monitoring for recurrence. Using available predictive models for prostate cancer recurrence, we examine whether current evidence supports a prolonged waiting period after radical prostatectomy and before renal transplantation. MATERIALS AND METHODS: A MedLine search was conducted to identify five series (published between 2000 and 2011), which examined biochemical recurrence (BCR) after prostatectomy for low-risk prostate cancer. The likelihood of BCR at one, two, and five yr after radical prostatectomy was identified for each series. RESULTS: Each of the analyzed series demonstrated that the likelihood of BCR after radical prostatectomy for low-risk prostate cancer was identical at one, two, and five yr and did not exceed 5%. CONCLUSIONS: The likelihood of BCR does not increase during the first five yr after radical prostatectomy for low-risk prostate cancer. Additionally, the risk of recurrence approaches zero during this period. Therefore, current evidence does not support the mandated waiting period of five yr before organ transplantation.


Subject(s)
Kidney Transplantation/statistics & numerical data , Neoplasm Recurrence, Local/diagnosis , Prostatectomy/mortality , Prostatic Neoplasms/surgery , Watchful Waiting , Humans , Male , Neoplasm Grading , Neoplasm Recurrence, Local/etiology , Neoplasm Recurrence, Local/mortality , Prognosis , Prostate-Specific Antigen/blood , Prostatectomy/adverse effects , Prostatic Neoplasms/complications , Prostatic Neoplasms/mortality , Retrospective Studies , Review Literature as Topic , Risk Assessment , Survival Rate
7.
R I Med J (2013) ; 106(7): 7-11, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37494618

ABSTRACT

Urinary diversion in renal transplant patients can take a variety of forms - bladder augmentation, continent cutaneous pouch, or intestinal conduits, to name a few. Herein, we present a unique case of an appendicocecal urinary diversion in a patient with history of end stage renal disease, pelvic radiation, and complex surgical history who underwent deceased-donor renal transplantation. During the renal transplant, the transplant ureterovesical anastomosis could not be performed due to inherent anatomical hindrances. A temporary modified cutaneous ureterostomy using a single-J stent was therefore used for drainage of the transplant kidney. Given that the cutaneous ureterostomy was not a durable, long-term option, we sought to develop a creative surgical solution. This report presents a unique case of urinary diversion post renal transplant and reviews the literature of renal transplantation in patients with anatomical abnormalities.


Subject(s)
Kidney Transplantation , Ureter , Urinary Diversion , Humans , Kidney , Ureterostomy , Ureter/surgery
8.
N Engl J Med ; 358(4): 353-61, 2008 Jan 24.
Article in English | MEDLINE | ID: mdl-18216355

ABSTRACT

Five patients with end-stage renal disease received combined bone marrow and kidney transplants from HLA single-haplotype mismatched living related donors, with the use of a nonmyeloablative preparative regimen. Transient chimerism and reversible capillary leak syndrome developed in all recipients. Irreversible humoral rejection occurred in one patient. In the other four recipients, it was possible to discontinue all immunosuppressive therapy 9 to 14 months after the transplantation, and renal function has remained stable for 2.0 to 5.3 years since transplantation. The T cells from these four recipients, tested in vitro, showed donor-specific unresponsiveness and in specimens from allograft biopsies, obtained after withdrawal of immunosuppressive therapy, there were high levels of P3 (FOXP3) messenger RNA (mRNA) but not granzyme B mRNA.


Subject(s)
Bone Marrow Transplantation , Kidney Failure, Chronic/surgery , Kidney Transplantation/immunology , Transplantation Chimera/immunology , Transplantation Tolerance/immunology , Adult , Biopsy , Combined Modality Therapy , Female , Graft Rejection/immunology , Granzymes/genetics , Granzymes/metabolism , Hepatocyte Nuclear Factor 3-alpha/genetics , Hepatocyte Nuclear Factor 3-alpha/metabolism , Histocompatibility Testing , Humans , Immunosuppression Therapy , Kidney/anatomy & histology , Kidney/ultrastructure , Male , Middle Aged , RNA, Messenger/isolation & purification , RNA, Messenger/metabolism , T-Lymphocytes/immunology , Transplantation Conditioning , Transplantation Immunology , Transplantation, Homologous/immunology
9.
J Vasc Surg ; 53(6): 1640-8, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21609797

ABSTRACT

BACKGROUND: Many patients on hemodialysis do not have adequate anatomy for native arteriovenous fistulas. In these patients, synthetic conduits remain an alternative option for permanent hemodialysis access. We sought to compare the standard cuffed expanded polytetrafluoroethylene (ePTFE) graft with the bovine carotid artery (BCA) graft. METHODS: This was a prospective, randomized controlled trial that was set in an academic medical center. We enrolled 26 patients in the BCA group and 27 patients in the ePTFE group. Primary, assisted primary, and secondary patency were calculated using the Kaplan-Meier method. Complications were monitored and are reported. RESULTS: Although there was no significant difference in secondary patency rates, primary and assisted primary patency rates were significantly higher in BCA than in the ePTFE grafts (60.5% vs 10.1% and 60.5% vs 20.8% at 1 year, respectively). The BCA graft survival advantage was most profound in the upper arm grafts with significantly higher primary and assisted patency rates (P < .0001 and .0005, respectively). The total number of interventions (upper arm grafts) and total number of angioplasties (overall and upper arm) required to maintain patency were significantly fewer in the BCA group. The most common complication was graft thrombosis which occurred 0.34 ± 0.09 times per patient year in the BCA group compared to 0.77 ± 0.16 times per patient year in the ePTFE group, P = .01. CONCLUSION: The BCA graft is an excellent option for patients on hemodialysis that are not suitable for native arteriovenous fistulas, as these grafts required fewer interventions than the ePTFE grafts to maintain patency.


Subject(s)
Kidney Failure, Chronic/surgery , Aged , Biocompatible Materials , Blood Vessel Prosthesis , Female , Graft Survival , Humans , Male , Middle Aged , Polytetrafluoroethylene , Prospective Studies , Renal Dialysis , Vascular Patency
10.
Infect Drug Resist ; 14: 3275-3286, 2021.
Article in English | MEDLINE | ID: mdl-34447256

ABSTRACT

PURPOSE: Studies have shown that multiple genes influence antibiotic susceptibility, but the relationship between genotypic and phenotypic antibiotic susceptibility is unclear. We sought to analyze the concordance between the presence of antibiotic resistance (ABR) genes and antibiotic susceptibility results in urine samples collected from patients with symptomatic urinary tract infection (UTI). PATIENTS AND METHODS: Urine samples were collected from patients presenting to 37 geographically disparate urology clinics across the United States from July 2018 to February 2019. Multiplex polymerase chain reaction was used to detect 27 ABR genes. In samples containing at least one culturable organism at a concentration of ≥ 104 cells per mL, pooled antibiotic susceptibility testing (P-AST), which involves simultaneous growing all detected bacteria together in the presence of antibiotic and then measure susceptibility, was performed against 14 antibiotics. The concordance rate between the ABR genes and the P-AST results was generated for the overall group. The concordance rates for each antibiotic between monomicrobial and polymicrobial infection were compared using chi-square test. RESULTS: Results from ABR gene detection and P-AST of urine samples from 1155 patients were included in the concordance analysis. Overall, there was a 60% concordance between the presence or absence of ABR genes and corresponding antimicrobial susceptibility with a range of 49-78% across antibiotic classes. Vancomycin, meropenem, and piperacillin/tazobactam showed significantly lower concordance rates in polymicrobial infections than in monomicrobial infections. CONCLUSION: Given the 40% discordance rate, the detection of ABR genes alone may not provide reliable data to make informed clinical decisions in UTI management. However, when used in conjunction with susceptibility testing, ABR gene data can offer valuable clinical information for antibiotic stewardship.

12.
Exp Clin Transplant ; 17(1): 11-17, 2019 02.
Article in English | MEDLINE | ID: mdl-29292685

ABSTRACT

OBJECTIVES: Lower urinary tract dysfunction can lead to chronic kidney disease, which, despite surgical intervention, will progress to end-stage renal disease, requiring dialysis. Urologic pathology may damage a transplanted kidney, limiting patient and graft survival. Although smaller studies have suggested that urinary tract dysfunction does not affect graft or patient survival, this is not universally accepted. Northern Ireland has historically had the highest incidence of neural tube defects in Europe, giving rich local experience in caring for patients with lower urinary tract dysfunction. Here, we analyzed outcomes of renal transplant recipients with lower urinary tract dysfunction versus control recipients. MATERIALS AND METHODS: We identified 3 groups of kidney transplant recipients treated between 2001 and 2010; those in group 1 had end-stage renal disease due to lower urinary tract dysfunction with prior intervention (urologic surgery, long-term catheter, or intermittent self-catheterization), group 2 had end-stage renal disease secondary to lower urinary tract dysfunction without intervention, and group 3 had end-stage renal disease due to polycystic kidney disease (chosen as a relatively healthy control cohort without comorbid burden of other causes of end-stage renal disease such as diabetes). The primary outcome measured, graft survival, was death censored, with graft loss defined as requirement for renal replacement therapy or retransplant. Secondary outcomes included patient survival and graft function. RESULTS: In 150 study patients (16 patients in group 1, 64 in group 2, and 70 in group 3), 5-year death-censored graft survival was 93.75%, 90.6%, and 92.9%, respectively, with no significant differences in graft failure among groups (Cox proportional hazards model). Five-year patient survival was 100%, 100%, and 94.3%, respectively. CONCLUSIONS: Individuals with a history of lower urinary tract dysfunction had graft and patient survival rates similar to the control group. When appropriately treated, lower urinary tract dysfunction is not a barrier to successful renal transplant.


Subject(s)
Kidney Failure, Chronic/surgery , Kidney Transplantation , Lower Urinary Tract Symptoms/complications , Adult , Clinical Decision-Making , Databases, Factual , Female , Graft Survival , Humans , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/etiology , Kidney Transplantation/adverse effects , Kidney Transplantation/mortality , Lower Urinary Tract Symptoms/diagnosis , Lower Urinary Tract Symptoms/mortality , Lower Urinary Tract Symptoms/therapy , Male , Middle Aged , Patient Selection , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Young Adult
13.
Transplantation ; 85(11): 1588-94, 2008 Jun 15.
Article in English | MEDLINE | ID: mdl-18551064

ABSTRACT

BACKGROUND: Compared with standard donors, kidneys recovered from donors after cardiac death (DCD) exhibit higher rates of delayed graft function (DGF), and DCD livers demonstrate higher rates of biliary ischemia, graft loss, and worse patient survival. Current practice limits the use of these organs based on time from donor extubation to asystole, but data to support this is incomplete. We hypothesized that donor postextubation parameters, including duration and severity of hemodynamic instability or hypoxia might be a better predictor of subsequent graft function. METHODS: We performed a retrospective examination of the New England Organ Bank DCD database, concentrating on donor factors including vital signs after withdrawal of support. RESULTS: Prolonged, severe hypotension in the postextubation period was a better predictor of subsequent organ function that time from extubation to asystole. For DCD kidneys, this manifested as a trend toward increased DGF. For DCD livers, this manifested as increased rates of poor outcomes. Maximizing the predictive value of this test in the liver cohort suggested that greater than 15 min between the time when the donor systolic blood pressure drops below 50 mm Hg and flush correlates with increased rates of diffuse biliary ischemia, graft loss, or death. Donor age also correlated with worse outcome. CONCLUSIONS: Time between profound instability and cold perfusion is a better predictor of outcome than time from extubation to asystole. If validated, this information could be used to predict DGF after DCD renal transplant and improve outcomes after DCD liver transplant.


Subject(s)
Death , Hypotension/etiology , Kidney Transplantation/physiology , Liver Transplantation/physiology , Tissue Donors , Tissue and Organ Procurement/methods , Ventilator Weaning/adverse effects , Adult , Age Factors , Blood Pressure/physiology , Female , Follow-Up Studies , Humans , Hypotension/epidemiology , Hypotension/physiopathology , Incidence , Intubation, Intratracheal , Kidney Transplantation/methods , Liver Transplantation/methods , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Survival Rate/trends , United States/epidemiology
14.
World J Nephrol ; 6(1): 45-52, 2017 Jan 06.
Article in English | MEDLINE | ID: mdl-28101451

ABSTRACT

AIM: To compare laparoscopic and open living donor nephrectomy, based on the results from a single center during a decade. METHODS: This is a retrospective review of all living donor nephrectomies performed at the Massachusetts General Hospital, Harvard Medical School, Boston, between 1/1998 - 12/2009. Overall there were 490 living donors, with 279 undergoing laparoscopic living donor nephrectomy (LLDN) and 211 undergoing open donor nephrectomy (OLDN). Demographic data, operating room time, the effect of the learning curve, the number of conversions from laparoscopic to open surgery, donor preoperative glomerular filtration rate and creatinine (Cr), donor and recipient postoperative Cr, delayed graft function and donor complications were analyzed. Statistical analysis was performed. RESULTS: Overall there was no statistically significant difference between the LLDN and the OLDN groups regarding operating time, donor preoperative renal function, donor and recipient postoperative kidney function, delayed graft function or the incidence of major complications. When the last 100 laparoscopic cases were analyzed, there was a statistically significant difference regarding operating time in favor of the LLDN, pointing out the importance of the learning curve. Furthermore, another significant difference between the two groups was the decreased length of stay for the LLDN (2.87 d for LLDN vs 3.6 d for OLDN). CONCLUSION: Recognizing the importance of the learning curve, this paper provides evidence that LLDN has a safety profile comparable to OLDN and decreased length of stay for the donor.

15.
Cell Transplant ; 25(7): 1331-41, 2016.
Article in English | MEDLINE | ID: mdl-26337731

ABSTRACT

We have previously reported successful induction of transient mixed chimerism and long-term acceptance of renal allografts in MHC mismatched nonhuman primates. In this study, we attempted to extend this tolerance induction approach to islet allografts. A total of eight recipients underwent MHC mismatched combined islet and bone marrow (BM) transplantation after induction of diabetes by streptozotocin. Three recipients were treated after a nonmyeloablative conditioning regimen that included low-dose total body and thymic irradiation, horse Atgam (ATG), six doses of anti-CD154 monoclonal antibody (mAb), and a 1-month course of cyclosporine (CyA) (Islet A). In Islet B, anti-CD8 mAb was administered in place of CyA. In Islet C, two recipients were treated with Islet B, but without ATG. The results were compared with previously reported results of eight cynomolgus monkeys that received combined kidney and BM transplantation (Kidney A) following the same conditioning regimen used in Islet A. The majority of kidney/BM recipients achieved long-term renal allograft survival after induction of transient chimerism. However, prolonged islet survival was not achieved in similarly conditioned islet/BM recipients (Islet A), despite induction of comparable levels of chimerism. In order to rule out islet allograft loss due to CyA toxicity, three recipients were treated with anti-CD8 mAb in place of CyA. Although these recipients developed significantly superior mixed chimerism and more prolonged islet allograft survival (61, 103, and 113 days), islet function was lost soon after the disappearance of chimerism. In Islet C recipients, neither prolonged chimerism nor islet survival was observed (30 and 40 days). Significant improvement of mixed chimerism induction and islet allograft survival were achieved with a CyA-free regimen that included anti-CD8 mAb. However, unlike the kidney allograft, islet allograft tolerance was not induced with transient chimerism. Induction of more durable mixed chimerism may be necessary for induction of islet allograft tolerance.


Subject(s)
Allografts/physiology , Bone Marrow Transplantation , Chimerism , Islets of Langerhans Transplantation , Kidney Transplantation , Transplantation Chimera , Allografts/drug effects , Animals , Antibodies, Monoclonal/metabolism , Chimerism/drug effects , Cyclosporine/pharmacology , Cytokines/blood , Graft Survival/drug effects , Immune Tolerance/drug effects , Macaca fascicularis , Male , Transplantation Conditioning
16.
Transplantation ; 80(12): 1791-804, 2005 Dec 27.
Article in English | MEDLINE | ID: mdl-16378076

ABSTRACT

BACKGROUND: In rodents, spleen allotransplantation (SpTx) induces tolerance. We investigated the induction of chimerism and donor-specific unresponsiveness following pig SpTx. METHODS: Thirteen pigs underwent splenectomy (day 0); all received a blood transfusion. In 11/13 pigs, SpTx was performed across a MHC class I (n=1) or full (n=10) barrier; two control pigs received no SpTx. All pigs were monitored for chimerism, and anti-donor immune responses, including suppressor assays. Four pigs (two asplenic controls and two with SpTx) underwent delayed donor-matched kidney transplantation without immunosuppression. RESULTS: Six of the 11 spleen grafts were lost from rejection (n=5) or splenic vein thrombosis (n=1), and five remained viable. All 11 SpTx recipients developed multilineage chimerism, but chimerism was rapidly lost if the graft failed. Two control pigs showed <6% blood chimerism for 4 and 11 days only. Pigs with functioning spleen grafts had multilineage chimerism in blood, thymus and bone marrow for at least 2-6 months, without graft-versus-host disease. These pigs developed in vitro donor-specific hyporesponsiveness and suppression. In 2 pigs tolerant to the spleen graft, donor MHC-matched kidney grafts survived for >4 and >7 months in the absence of exogenous immunosuppression; in two asplenic pigs, kidney grafts were rejected on days 4 and 15. CONCLUSIONS: Successful SpTx can result in hematopoietic cell engraftment and in vitro donor-specific unresponsiveness, enabling prolonged survival of subsequent donor-matched kidney grafts without immunosuppression.


Subject(s)
Kidney Transplantation/immunology , Major Histocompatibility Complex/immunology , Spleen/transplantation , Transplantation Chimera , Animals , Blood Transfusion , Colony-Forming Units Assay , Graft Rejection/immunology , Histocompatibility Testing , Immunosuppressive Agents/blood , Immunosuppressive Agents/therapeutic use , Kidney/cytology , Lymph Nodes/cytology , Monitoring, Physiologic , Polymerase Chain Reaction , Spleen/cytology , Splenectomy , Swine , Swine, Miniature , Transplantation, Homologous/immunology , Transplantation, Homologous/physiology
17.
Urology ; 86(4): 716-20, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26232691

ABSTRACT

OBJECTIVE: To examine the association between urinary phytoestrogens and self-reported urinary incontinence in postmenopausal women in the United States using a large, cross-sectional, population-based cohort survey. METHODS: Data were analyzed for 1789 postmenopausal women aged 50 years or older who participated in one of the 2001-2010 cycles of National Health and Nutrition Examination Survey and underwent measurement of 4 isoflavone (soy derived) and 2 lignan (flax derived) phytoestrogens in their urine. Incontinence was defined as self-reported stress, urge, other, or mixed incontinence. Urine phytoestrogen concentrations were examined in weighted, multivariate logistic regression models for association with each of the lower urinary tract symptoms. All models were adjusted for age, body mass index, diabetes, race, smoking, and parity. RESULTS: Increasing urine concentrations of the lignan phytoestrogen enterodiol was associated with decreased likelihood of urge (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.85-0.99), mixed (OR, 0.90; 95% CI, 0.82-0.98), and other (OR, 0.90; 95% CI, 0.81-0.99) incontinence, whereas increasing urine concentrations of the lignan phytoestrogen enterolactone was associated with decreased likelihood of urge (OR, 0.92; 95% CI, 0.86-0.99) and mixed (OR, 0.91; 95% CI, 0.84-0.99) incontinence. No association was observed between any isoflavone phytoestrogens and types of incontinence. CONCLUSION: This study demonstrates that lignan phytoestrogens may have a protective effect against incontinence in postmenopausal women. Prospective clinical and laboratory studies are warranted to investigate the mechanism of this relationship.


Subject(s)
Lignans/urine , Postmenopause/urine , Urinary Incontinence/epidemiology , Aged , Body Mass Index , Cross-Sectional Studies , Female , Humans , Massachusetts/epidemiology , Middle Aged , Morbidity/trends , Prospective Studies , Self Report , Urinary Incontinence/urine
18.
Transplantation ; 76(5): 798-802, 2003 Sep 15.
Article in English | MEDLINE | ID: mdl-14501856

ABSTRACT

BACKGROUND: Delayed graft function (DGF) is frequently observed in recipients of cadaveric renal transplants. Previous retrospective or nonrandomized studies have suggested that intraoperative administration of polyclonal antithymocyte preparations may reduce the incidence of DGF, possibly by decreasing ischemia-reperfusion injury. METHODS: We performed a prospective randomized study of Thymoglobulin induction therapy in adult cadaveric renal transplant recipients. Between January 2001 and January 2002, 58 adult cadaveric renal transplant recipients were randomized to receive intraoperative or postoperative Thymoglobulin induction therapy. Three to six doses of Thymoglobulin (1 mg/kg/dose) were administered during the first week posttransplant. Baseline immunosuppression consisted of tacrolimus (54 of 58) or cyclosporine A (4 of 58), steroids, and mycophenolate mofetil. DGF was defined by the requirement for hemodialysis within the first week posttransplant. RESULTS: There were no significant differences between the two groups in recipient demographics, donor age, cold ischemia time, or total number of doses of Thymoglobulin administered. Intraoperative Thymoglobulin administration was associated with significantly less DGF and a lower mean serum creatinine on postoperative days 10 and 14 (P<0.05). Posttransplant length of stay was also significantly shorter for the intraoperative Thymoglobulin patient group. The acute rejection rate was also lower in the intraoperative treatment group but this did not achieve statistical significance. There was no difference in the incidence of cytomegalovirus disease between the two groups. CONCLUSIONS: The results of this study indicate that intraoperative Thymoglobulin administration, in adult cadaveric renal transplant recipients, is associated with a significant decrease in DGF, better early allograft function in the first month posttransplant, and a decreased posttransplant hospital length of stay.


Subject(s)
Antilymphocyte Serum/administration & dosage , Intraoperative Care , Kidney Transplantation , Postoperative Care , Acute Disease , Adult , Cadaver , Chronic Disease , Female , Graft Rejection/epidemiology , Graft Rejection/immunology , Graft Rejection/prevention & control , Humans , Incidence , Kidney/physiology , Length of Stay , Male , Middle Aged , Prospective Studies , Treatment Outcome
19.
Ann Transplant ; 17(1): 117-21, 2012.
Article in English | MEDLINE | ID: mdl-22466917

ABSTRACT

BACKGROUND: Uncontrolled intracranial hypertension can lead to cerebral herniation and death in patients with acute liver failure. CASE REPORT: A 26-year-old female was admitted for acute liver failure following inadvertent acetaminophen overdose. The pH on admission was 6.9. Her neurologic status precipitously deteriorated and she was listed for liver transplantation. An intracranial pressure (ICP) monitoring catheter was inserted, which revealed a pressure >60 mmHg. After neurointensive care treatment, ICP was lowered and an emergency left lobe living donor liver transplant was performed. Intraoperative management of the ICP, which rose to 80 mmHg during the explant phase, was achieved by therapy with barbiturates and hypothermia. After surgery, hepatic function improved initially, but 7 days post transplantation the graft showed signs of acute failure. The pathology report of a liver biopsy suggested acute rejection and liver retransplantation using a deceased donor liver was then carried out. The postoperative course was uneventful and the patient recovered completely without any residual neurologic deficits. CONCLUSIONS: This case states that favourable outcomes can result from sub-optimal starting points, and that the human brain has the ability to overcome extremely adverse conditions. Critical in this effort is the role of proper neuromonitoring which helps implement the appropriate treatment measures.


Subject(s)
Hypertension, Malignant/etiology , Hypertension, Malignant/surgery , Liver Failure, Acute/complications , Liver Failure, Acute/surgery , Liver Transplantation , Adult , Female , Hepatic Encephalopathy/complications , Hepatic Encephalopathy/surgery , Humans , Hypertension, Malignant/physiopathology , Intracranial Hypertension/complications , Intracranial Hypertension/surgery , Intracranial Pressure , Liver Failure, Acute/physiopathology , Liver Transplantation/physiology , Monitoring, Intraoperative/methods , Reoperation
20.
Arch Surg ; 144(5): 472-5, 2009 May.
Article in English | MEDLINE | ID: mdl-19451491

ABSTRACT

OBJECTIVE: To compare the outcome of living donor kidney transplantation using allografts with a single artery with that observed in recipients of allografts with multiple arteries. DESIGN: Retrospective analysis. SETTING: Tertiary center. PATIENTS: Three hundred fifty patients who underwent living donor kidney transplantation from January 2000 to March 2007. INTERVENTIONS: Living donor kidney transplantation. MAIN OUTCOME MEASURES: Surgical complications and allograft survival. RESULTS: Three hundred nineteen allografts (91.1%) had a single artery (group 1) and 31 (8.9%) had multiple arteries (group 2), including 2 arteries in 21 grafts (67.8%), 3 arteries in 6 (19.3%), and 4 arteries in 4 grafts (12.9%). The operative time was shorter in group 1 compared with group 2 (mean [SD], 173 [35] vs 259 [48] minutes; P < .001). The overall surgical complication rate in groups 1 and 2 was comparable (9.6% vs 9.7%; vascular, 2.8% vs 3.2%; urological, 1.6% vs 3.2%; symptomatic lymphocele, 2.8% vs 3.2%; and wound infections, 2.8% vs 3.2%). The actuarial 1- and 5-year allograft survival rates were comparable in both groups (98.4% and 91.5% in group 1 and 96.8% and 87.1% in group 2). A significant increased use of allografts with multiple arteries has been observed in recent years: 7.8% (n = 10) in grafts that were procured by open technique (n = 127), 4.1% (n = 5) during our initial experience with laparoscopic nephrectomy (n = 123), and 16% (n = 16) in the most recent 100 cases (P < .01). CONCLUSIONS: Living donor kidney transplantation in the presence of multiple renal arteries is feasible and safe. Additionally, graft survival and graft function are not adversely affected by the presence of multiple renal arteries in grafts procured laparoscopically. Recently, there has been an increased use of kidneys with multiple arteries with excellent results.


Subject(s)
Kidney Transplantation/methods , Kidney/blood supply , Living Donors , Nephrectomy/methods , Angiography , Female , Graft Survival , Humans , Kidney/surgery , Laparoscopy/methods , Male , Postoperative Complications , Retrospective Studies , Survival Rate , Treatment Outcome
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