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Research paper thumbnail of Obesity and Outcome Following Renal Transplantation

American Journal of Transplantation Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, Feb 1, 2006

Single institution series have demonstrated that obese patients have higher rates of wound infect... more Single institution series have demonstrated that obese patients have higher rates of wound infection and delayed graft function (DGF), but similar rates of graft survival. We used UNOS data to determine whether obesity affects outcome following renal transplantation. From the UNOS database, we identified patients who underwent primary kidney-only transplantation between 1997 and 1999. Recipient and donor body mass index (BMI) was categorized as underweight (BMI = 35). We correlated BMI with intermediate measures of graft outcome and overall graft survival, and created multivariate models to evaluate the independent effect of BMI on graft outcome, adjusting for factors known to affect graft success. The study sample comprised 27 377 recipients. Older age, female sex, African American race and increased comorbidity were associated with obesity (p = 0.07). Recipient obesity is associated with an increased risk of DGF and decreased graft survival following renal transplantation.

Research paper thumbnail of The evolving role of alemtuzumab (Campath-1H) in renal transplantation

Drug Design, Development and Therapy

The introduction of new immunosuppressive agents into clinical transplantation in the 1990s has r... more The introduction of new immunosuppressive agents into clinical transplantation in the 1990s has resulted in excellent short-term graft survival. Nonetheless, extended long-term graft outcomes have not been achieved due in part to the nephrotoxic effects of calcineurin inhibitors (CNIs) and the adverse effects of steroid on cardiovascular disease risk factors. Induction therapy with lymphocyte depleting antibodies has originally been introduced into renal transplantation to provide intense immunosuppression in the early post-transplant period to prevent allograft rejection. Over the past half decade, induction therapy with both non-lymphocyte depleting (basiliximab and daclizumab) and lymphocyte-depleting antibodies (antithymocyte antibodies, OKT3, alemtuzumab) has increasingly been utilized in steroid or CNI sparing protocols in the early postoperative period. Alemtuzumab is a humanized monoclonal antibody targeted against CD52 on the surface of circulatory mononuclear cells. The ab...

Research paper thumbnail of MP54-20 Incidence of Dextranomer-Hyaluronic Acid Site Calcification is Greater Than Expected

The Journal of Urology, 2015

Research paper thumbnail of Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia

Blood, 1989

To assess the influence of graft-versus-host disease (GVHD) on recurrent leukemia and survival af... more To assess the influence of graft-versus-host disease (GVHD) on recurrent leukemia and survival after allogeneic marrow transplantation, we studied 1,202 patients with acute nonlymphocytic leukemia (ANL), acute lymphocytic leukemia (ALL), and chronic myelogenous leukemia (CML) given unmodified marrow grafts from HLA-identical siblings. Proportional hazards regression models using acute GVHD and chronic GVHD as time-dependent covariates demonstrated a significant association of GVHD with a decreased relative risk (RR, 0.33 to 0.42) of relapse in patients with ANL, ALL, and CML transplanted in advanced disease. Among patients developing either acute or chronic GVHD, treatment failure (that is, mortality or relapse) was decreased in patients with ALL transplanted in relapse (RR = 0.70, P less than .033) and CML in blast crisis (RR = 0.37, P less than .009). This effect was independent of age, sex, preparative regimen, GVHD prophylaxis, or length of follow-up. Five-year actuarial estimat...

Research paper thumbnail of Hepatic Transplantation in 1393 Consecutive Patients

Research paper thumbnail of Allochimeric Class I MHC Molecules Prevent Chronic Rejection and Attenuate Alloantibody RESPONSES1

Transplantation, 2001

We have shown that treatment with molecularly engineered, allochimeric [alpha1 hl/u]-RT1.Aa class... more We have shown that treatment with molecularly engineered, allochimeric [alpha1 hl/u]-RT1.Aa class I MHC antigens bearing donor-type Wistar-Furth (WF, RT1.Au) amino acid substitutions for host-type ACI (RTI.Aa) sequences in the alpha1-helical region induces donor-specific tolerance to cardiac allografts in rat recipients. This study examined the effect of allochimeric molecules on the development of chronic rejection. Allochimeric [alpha1 hl/u]-RT1.Aa class I MHC antigenic extracts (1 mg) were administered via the portal vein into ACI recipients of WF hearts on the day of transplantation in conjunction with subtherapeutic oral cyclosporine (CsA, 10 mg/kg/day, days 0-2). Control groups included recipients of syngeneic grafts and ACI recipients of WF heart allografts treated with high-dose CsA (10 mg/kg/day, days 0-6). WF hearts in ACI rats receiving 7 days of CsA exhibited myocardial fibrosis, perivascular inflammation, and intimal hyperplasia at day 80. At day 120, these grafts displayed severe chronic rejection with global architectural disorganization, ventricular fibrosis, intimal hyperplasia, and progressive luminal narrowing. In contrast, WF hearts in rats treated with [alpha1 hl/u]-RT1.Aa molecules revealed only mild perivascular fibrosis, minimal intimal thickening, and preserved myocardial architecture. Alloantibody analysis demonstrated no IgM alloantibodies in all groups. An attenuated, but detectable, anti-WF IgG response was present in recipients receiving allochimeric molecules, with IgG1 and IgG2a subclasses predominating. Immunohistochemical analysis of allografts demonstrated minimal T cell infiltration and IgG binding to vascular endothelium. Treatment with allochimeric molecules prevents the development of chronic rejection. Such effect may be in part caused by deviation of host alloantibody responses.

Research paper thumbnail of Splenosis Presenting as a Right Suprarenal Retroperitoneal Mass

Research paper thumbnail of Amelioration of hepatic ischemia/reperfusion injury using indolepropionic acid

Transplantation Proceedings, 2002

Research paper thumbnail of Retransplantation for Recurrent Hepatitis C Following Tacrolimus or Cyclosporine Immunosuppression

Transplantation Proceedings, 1998

Research paper thumbnail of Allochimeric class I MHC inhibits chronic rejection in cardiac allografts

Transplantation Proceedings, 2001

Research paper thumbnail of Induction of “Infectious” Tolerance by Allochimeric Class I MHC Molecules: Evidence of Immunoregulatory T Cells and Limited Usage of T Cell Receptor Vβ Genes

Research paper thumbnail of Tolerance Induction by a Single Allochimeric Molecule to Two Different Rat Strains: Mechanisms of Long-Term Allograft Acceptance

Research paper thumbnail of Treatment with Allochimeric Class I MHC Molecules Inhibits Chronic Rejection and Attenuates Alloantibody Responses in Rat Cardiac Allograft Recipients

Research paper thumbnail of Sirolimus-Associated Pulmonary Toxicity

Transplantation, 2004

Pulmonary toxicity has recently been recognized as a potentially serious complication associated ... more Pulmonary toxicity has recently been recognized as a potentially serious complication associated with sirolimus therapy. We further detail this condition on the basis of our own cases and those reported in the literature. We report three cases of suspected sirolimus-induced pulmonary toxicity that occurred in three renal transplant recipients and searched PubMed for all previously reported cases. Including our current cases, 43 patients with sirolimus-induced pulmonary toxicity have now been reported. Clinical data were incomplete in 28 cases. Analysis of available data for 15 patients revealed that the most commonly presenting symptoms were dyspnea on exertion and dry cough followed by fatigue and fever. Chest radiographs and high-resolution computed tomography scans commonly revealed bilateral patchy or diffuse alveolo-interstitial infiltrates. Bronchoalveolar fluid analysis and lung biopsy in selected case reports revealed several distinct histologic features, including lymphocytic alveolitis, lymphocytic interstitial pneumonitis, bronchoalveolar obliterans organizing pneumonia, focal fibrosis, pulmonary alveolar hemorrhage, or a combination thereof. The diagnosis of sirolimus-associated pulmonary toxicity was made after an exhaustive work-up to exclude infectious causes and other pulmonary disease. Sirolimus discontinuation or dose reduction resulted in clinical and radiologic improvement in all 15 patients within 3 weeks. The temporal relationship between sirolimus exposure and onset of pulmonary symptoms in the absence of infectious causes and other alternative pulmonary disease and the associated clinical and radiologic improvement after its cessation suggests a causal relationship. Because the use of sirolimus in organ transplantation has become more widespread, clinicians must remain vigilant to its potential pulmonary complication.

Research paper thumbnail of Impact of Operative Events on the Outcome of Primary Hepatic Transplantation in Adults

Research paper thumbnail of The Socioeconomic Status of Living Unrelated Renal Transplant Donors in the Us is Consistent with Altruistic Motivation

Transplantation Journal, 2010

Research paper thumbnail of Preoperative Factors Associated with Outcome and Their Impact on Resource Use in 1148 Consecutive Primary Liver Transplants

Transplantation, 2001

Hepatic transplantation is a highly effective but costly treatment for end-stage hepatic dysfunct... more Hepatic transplantation is a highly effective but costly treatment for end-stage hepatic dysfunction. One approach to improve efficiency in the use of scarce organs for transplantation is to identify preoperative factors that are associated with poor outcome posttransplantation. This may assist both in selecting patients optimal for transplantation and in identifying strategies to improve survival. In the present work, we retrospectively reviewed consecutive liver transplants performed at the University of California at Los Angeles during a 6-year period and determined preoperative variables that were associated with outcome in primary grafts. In addition, we used the hospital's cost accounting database to determine the impact of these variables on the degree of resource use by high-risk patients. We found five variables to have independent prognostic value in predicting graft survival after primary liver transplantation: (1) donor age, (2) recipient age, (3) donor sodium, (4) recipient creatinine, and (5) recipient ventilator requirement pretransplant. Recipient ventilator requirement and elevated creatinine were associated with significant increases in resource use during the transplant admission. Patients at high risk for graft failure and costly transplants can be identified preoperatively by a set of parameters that are readily available, noninvasive, and inexpensive. Selection of recipients on the basis of these data would improve the efficiency of liver transplantation and reduce its cost.

Research paper thumbnail of Long-Term Comparative Outcomes Between 2 Common Ureteroneocystostomy Techniques for Renal Transplantation

The Journal of Urology, 2007

We compared the incidence of ureteral complications between the classic (Lich-Gregoir) technique ... more We compared the incidence of ureteral complications between the classic (Lich-Gregoir) technique and the recently popularized single stitch (Shanfield) technique in renal transplantation. Materials and Methods: The charts of 721 consecutive transplant recipients from May 1999 to July 2002 were retrospectively reviewed. Ureteral and nonureteral complications were reviewed at 3 to 5-year followup. Results: Of the 721 recipients evaluated 713 were included in the study. There were 360 recipients in the Lich-Gregoir group and 353 in the Shanfield group. A significantly higher rate of ureteral complications occurred in the Shanfield group compared to the Lich-Gregoir group (15.6% vs 3.9%, p Ͻ0.0001). The Shanfield group consisted of 20 patients with ureteral leakage, 21 with hematuria, 11 with strictures and 3 who had ureteral stones. The Lich-Gregoir group had 8 patients with ureteral leakage, 5 with hematuria and 1 with a stricture. In comparison, urinary tract infections, delayed graft function and rejection rates were not significantly different between the 2 groups (p ϭ 0.76, 0.12 and 0.19, respectively).

Research paper thumbnail of Selective Use of Voiding Cystourethrography in Children Undergoing Renal Transplant Evaluation

The Journal of Urology, 2009

UTI ϭ urinary tract infection VCUG ϭ voiding cystourethrogram VUR ϭ vesicoureteral reflux ).

Research paper thumbnail of The Socioeconomic Status of Donors and Recipients of Living Unrelated Renal Transplants in the United States

The Journal of Urology, 2012

LRRT ϭ living related renal transplantation LURT ϭ living unrelated renal transplantation SES ϭ s... more LRRT ϭ living related renal transplantation LURT ϭ living unrelated renal transplantation SES ϭ socioeconomic status SESI ϭ SES index UNOS ϭ United Network for Organ Sharing. ).

Research paper thumbnail of Obesity and Outcome Following Renal Transplantation

American Journal of Transplantation Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, Feb 1, 2006

Single institution series have demonstrated that obese patients have higher rates of wound infect... more Single institution series have demonstrated that obese patients have higher rates of wound infection and delayed graft function (DGF), but similar rates of graft survival. We used UNOS data to determine whether obesity affects outcome following renal transplantation. From the UNOS database, we identified patients who underwent primary kidney-only transplantation between 1997 and 1999. Recipient and donor body mass index (BMI) was categorized as underweight (BMI = 35). We correlated BMI with intermediate measures of graft outcome and overall graft survival, and created multivariate models to evaluate the independent effect of BMI on graft outcome, adjusting for factors known to affect graft success. The study sample comprised 27 377 recipients. Older age, female sex, African American race and increased comorbidity were associated with obesity (p = 0.07). Recipient obesity is associated with an increased risk of DGF and decreased graft survival following renal transplantation.

Research paper thumbnail of The evolving role of alemtuzumab (Campath-1H) in renal transplantation

Drug Design, Development and Therapy

The introduction of new immunosuppressive agents into clinical transplantation in the 1990s has r... more The introduction of new immunosuppressive agents into clinical transplantation in the 1990s has resulted in excellent short-term graft survival. Nonetheless, extended long-term graft outcomes have not been achieved due in part to the nephrotoxic effects of calcineurin inhibitors (CNIs) and the adverse effects of steroid on cardiovascular disease risk factors. Induction therapy with lymphocyte depleting antibodies has originally been introduced into renal transplantation to provide intense immunosuppression in the early post-transplant period to prevent allograft rejection. Over the past half decade, induction therapy with both non-lymphocyte depleting (basiliximab and daclizumab) and lymphocyte-depleting antibodies (antithymocyte antibodies, OKT3, alemtuzumab) has increasingly been utilized in steroid or CNI sparing protocols in the early postoperative period. Alemtuzumab is a humanized monoclonal antibody targeted against CD52 on the surface of circulatory mononuclear cells. The ab...

Research paper thumbnail of MP54-20 Incidence of Dextranomer-Hyaluronic Acid Site Calcification is Greater Than Expected

The Journal of Urology, 2015

Research paper thumbnail of Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia

Blood, 1989

To assess the influence of graft-versus-host disease (GVHD) on recurrent leukemia and survival af... more To assess the influence of graft-versus-host disease (GVHD) on recurrent leukemia and survival after allogeneic marrow transplantation, we studied 1,202 patients with acute nonlymphocytic leukemia (ANL), acute lymphocytic leukemia (ALL), and chronic myelogenous leukemia (CML) given unmodified marrow grafts from HLA-identical siblings. Proportional hazards regression models using acute GVHD and chronic GVHD as time-dependent covariates demonstrated a significant association of GVHD with a decreased relative risk (RR, 0.33 to 0.42) of relapse in patients with ANL, ALL, and CML transplanted in advanced disease. Among patients developing either acute or chronic GVHD, treatment failure (that is, mortality or relapse) was decreased in patients with ALL transplanted in relapse (RR = 0.70, P less than .033) and CML in blast crisis (RR = 0.37, P less than .009). This effect was independent of age, sex, preparative regimen, GVHD prophylaxis, or length of follow-up. Five-year actuarial estimat...

Research paper thumbnail of Hepatic Transplantation in 1393 Consecutive Patients

Research paper thumbnail of Allochimeric Class I MHC Molecules Prevent Chronic Rejection and Attenuate Alloantibody RESPONSES1

Transplantation, 2001

We have shown that treatment with molecularly engineered, allochimeric [alpha1 hl/u]-RT1.Aa class... more We have shown that treatment with molecularly engineered, allochimeric [alpha1 hl/u]-RT1.Aa class I MHC antigens bearing donor-type Wistar-Furth (WF, RT1.Au) amino acid substitutions for host-type ACI (RTI.Aa) sequences in the alpha1-helical region induces donor-specific tolerance to cardiac allografts in rat recipients. This study examined the effect of allochimeric molecules on the development of chronic rejection. Allochimeric [alpha1 hl/u]-RT1.Aa class I MHC antigenic extracts (1 mg) were administered via the portal vein into ACI recipients of WF hearts on the day of transplantation in conjunction with subtherapeutic oral cyclosporine (CsA, 10 mg/kg/day, days 0-2). Control groups included recipients of syngeneic grafts and ACI recipients of WF heart allografts treated with high-dose CsA (10 mg/kg/day, days 0-6). WF hearts in ACI rats receiving 7 days of CsA exhibited myocardial fibrosis, perivascular inflammation, and intimal hyperplasia at day 80. At day 120, these grafts displayed severe chronic rejection with global architectural disorganization, ventricular fibrosis, intimal hyperplasia, and progressive luminal narrowing. In contrast, WF hearts in rats treated with [alpha1 hl/u]-RT1.Aa molecules revealed only mild perivascular fibrosis, minimal intimal thickening, and preserved myocardial architecture. Alloantibody analysis demonstrated no IgM alloantibodies in all groups. An attenuated, but detectable, anti-WF IgG response was present in recipients receiving allochimeric molecules, with IgG1 and IgG2a subclasses predominating. Immunohistochemical analysis of allografts demonstrated minimal T cell infiltration and IgG binding to vascular endothelium. Treatment with allochimeric molecules prevents the development of chronic rejection. Such effect may be in part caused by deviation of host alloantibody responses.

Research paper thumbnail of Splenosis Presenting as a Right Suprarenal Retroperitoneal Mass

Research paper thumbnail of Amelioration of hepatic ischemia/reperfusion injury using indolepropionic acid

Transplantation Proceedings, 2002

Research paper thumbnail of Retransplantation for Recurrent Hepatitis C Following Tacrolimus or Cyclosporine Immunosuppression

Transplantation Proceedings, 1998

Research paper thumbnail of Allochimeric class I MHC inhibits chronic rejection in cardiac allografts

Transplantation Proceedings, 2001

Research paper thumbnail of Induction of “Infectious” Tolerance by Allochimeric Class I MHC Molecules: Evidence of Immunoregulatory T Cells and Limited Usage of T Cell Receptor Vβ Genes

Research paper thumbnail of Tolerance Induction by a Single Allochimeric Molecule to Two Different Rat Strains: Mechanisms of Long-Term Allograft Acceptance

Research paper thumbnail of Treatment with Allochimeric Class I MHC Molecules Inhibits Chronic Rejection and Attenuates Alloantibody Responses in Rat Cardiac Allograft Recipients

Research paper thumbnail of Sirolimus-Associated Pulmonary Toxicity

Transplantation, 2004

Pulmonary toxicity has recently been recognized as a potentially serious complication associated ... more Pulmonary toxicity has recently been recognized as a potentially serious complication associated with sirolimus therapy. We further detail this condition on the basis of our own cases and those reported in the literature. We report three cases of suspected sirolimus-induced pulmonary toxicity that occurred in three renal transplant recipients and searched PubMed for all previously reported cases. Including our current cases, 43 patients with sirolimus-induced pulmonary toxicity have now been reported. Clinical data were incomplete in 28 cases. Analysis of available data for 15 patients revealed that the most commonly presenting symptoms were dyspnea on exertion and dry cough followed by fatigue and fever. Chest radiographs and high-resolution computed tomography scans commonly revealed bilateral patchy or diffuse alveolo-interstitial infiltrates. Bronchoalveolar fluid analysis and lung biopsy in selected case reports revealed several distinct histologic features, including lymphocytic alveolitis, lymphocytic interstitial pneumonitis, bronchoalveolar obliterans organizing pneumonia, focal fibrosis, pulmonary alveolar hemorrhage, or a combination thereof. The diagnosis of sirolimus-associated pulmonary toxicity was made after an exhaustive work-up to exclude infectious causes and other pulmonary disease. Sirolimus discontinuation or dose reduction resulted in clinical and radiologic improvement in all 15 patients within 3 weeks. The temporal relationship between sirolimus exposure and onset of pulmonary symptoms in the absence of infectious causes and other alternative pulmonary disease and the associated clinical and radiologic improvement after its cessation suggests a causal relationship. Because the use of sirolimus in organ transplantation has become more widespread, clinicians must remain vigilant to its potential pulmonary complication.

Research paper thumbnail of Impact of Operative Events on the Outcome of Primary Hepatic Transplantation in Adults

Research paper thumbnail of The Socioeconomic Status of Living Unrelated Renal Transplant Donors in the Us is Consistent with Altruistic Motivation

Transplantation Journal, 2010

Research paper thumbnail of Preoperative Factors Associated with Outcome and Their Impact on Resource Use in 1148 Consecutive Primary Liver Transplants

Transplantation, 2001

Hepatic transplantation is a highly effective but costly treatment for end-stage hepatic dysfunct... more Hepatic transplantation is a highly effective but costly treatment for end-stage hepatic dysfunction. One approach to improve efficiency in the use of scarce organs for transplantation is to identify preoperative factors that are associated with poor outcome posttransplantation. This may assist both in selecting patients optimal for transplantation and in identifying strategies to improve survival. In the present work, we retrospectively reviewed consecutive liver transplants performed at the University of California at Los Angeles during a 6-year period and determined preoperative variables that were associated with outcome in primary grafts. In addition, we used the hospital's cost accounting database to determine the impact of these variables on the degree of resource use by high-risk patients. We found five variables to have independent prognostic value in predicting graft survival after primary liver transplantation: (1) donor age, (2) recipient age, (3) donor sodium, (4) recipient creatinine, and (5) recipient ventilator requirement pretransplant. Recipient ventilator requirement and elevated creatinine were associated with significant increases in resource use during the transplant admission. Patients at high risk for graft failure and costly transplants can be identified preoperatively by a set of parameters that are readily available, noninvasive, and inexpensive. Selection of recipients on the basis of these data would improve the efficiency of liver transplantation and reduce its cost.

Research paper thumbnail of Long-Term Comparative Outcomes Between 2 Common Ureteroneocystostomy Techniques for Renal Transplantation

The Journal of Urology, 2007

We compared the incidence of ureteral complications between the classic (Lich-Gregoir) technique ... more We compared the incidence of ureteral complications between the classic (Lich-Gregoir) technique and the recently popularized single stitch (Shanfield) technique in renal transplantation. Materials and Methods: The charts of 721 consecutive transplant recipients from May 1999 to July 2002 were retrospectively reviewed. Ureteral and nonureteral complications were reviewed at 3 to 5-year followup. Results: Of the 721 recipients evaluated 713 were included in the study. There were 360 recipients in the Lich-Gregoir group and 353 in the Shanfield group. A significantly higher rate of ureteral complications occurred in the Shanfield group compared to the Lich-Gregoir group (15.6% vs 3.9%, p Ͻ0.0001). The Shanfield group consisted of 20 patients with ureteral leakage, 21 with hematuria, 11 with strictures and 3 who had ureteral stones. The Lich-Gregoir group had 8 patients with ureteral leakage, 5 with hematuria and 1 with a stricture. In comparison, urinary tract infections, delayed graft function and rejection rates were not significantly different between the 2 groups (p ϭ 0.76, 0.12 and 0.19, respectively).

Research paper thumbnail of Selective Use of Voiding Cystourethrography in Children Undergoing Renal Transplant Evaluation

The Journal of Urology, 2009

UTI ϭ urinary tract infection VCUG ϭ voiding cystourethrogram VUR ϭ vesicoureteral reflux ).

Research paper thumbnail of The Socioeconomic Status of Donors and Recipients of Living Unrelated Renal Transplants in the United States

The Journal of Urology, 2012

LRRT ϭ living related renal transplantation LURT ϭ living unrelated renal transplantation SES ϭ s... more LRRT ϭ living related renal transplantation LURT ϭ living unrelated renal transplantation SES ϭ socioeconomic status SESI ϭ SES index UNOS ϭ United Network for Organ Sharing. ).