PubMed Health⌕ Search

Biomedical subjects

C T Van Buren

Publications and source records attributed to C T Van Buren.

At least 19 recordsLinked to original sources
PubMed2006

Fibromuscular dysplasia recurrence after kidney transplantation: case report.

We report the extremely rare recurrence of intimal fibroplasia, a rare form of fibromuscular dysplasia, in a kidney recipient at 6 months after transplantation from a living-related donor. The patient was successfully treated and maintains good kidney function, however, the case raises the question of whether kidneys with fibromuscular dysplasia should be included in the expanded criteria for kidney transplantation.

Adult↗
PubMed2005

Transplantation of single pediatric kidneys into adult recipients.

AIM: To evaluate the outcome of single pediatric kidneys transplanted into adult recipients. METHODS: A retrospective single-center review was performed of transplants from donors less than 5 years of age. Outcomes were compared with recipients of grafts from donors 18 to 45 years transplanted during the same time period. RESULTS: Thirty single renal transplants from pediatric donors and 117 transplants from adult donors between 18 and 45 years of age were performed during the study period. The mean age of the pediatric donors was 2.9 +/- 0.8 years versus 31.5 +/- 8.9 years for adult donors (P < .001). The mean age of the recipients of pediatric donors was 41.9 +/- 13 years versus 48 +/- 12.6 years for recipients of adult grafts (P = .020). The mean recipient weight of pediatric donors was 55.9 +/- 7.8 kg versus 78.0 +/- 17.7 kg for recipients of adult donors (P < .001). Sixty-six percent of pediatric donor recipients were of female gender compared to only 36% of adult donor recipients (P = .005). Death-censored actuarial graft survivals at 1 and 4 years for recipients of pediatric donor grafts were 90% and 85% compared to 93% and 85% for recipients of adult donor grafts (P = NS). The mean calculated creatinine clearances of adult donor graft recipients at 1 and 4 years posttransplantation were 70.8 +/- 26.5 and 73.7 +/- 27.2 mL/min, respectively, compared to 50.3 +/- 20.1 and 56.3 +/- 21.4 mL/min for pediatric donor grafts (P < .01 at 1 and 4 years). CONCLUSION: The use of single pediatric donor kidneys provides an excellent opportunity to safely expand the donor pool.

Actuarial Analysis↗
PubMed2005

Rabbit antithymocyte globulin: a postoperative risk factor for sirolimus-treated renal transplant patients?

AIMS: Randomized controlled studies suggest an increased incidence of perioperative wound complications among sirolimus-treated renal transplant patients. The present study analyzed the effect of rabbit antithymocyte globulin (rATG) on these postoperative complications. METHODS: Four hundred and twelve renal transplants were performed and managed postoperatively at two University-affiliated hospitals between January 1, 2001, and December 31, 2003. The patients received corticosteroids and Sirolimus, with delayed introduction of cyclosporine when the serum creatinine had decreased below 2.5 mg/dL. Two groups of patients were discriminated: group 1 received Basiliximab 20 mg on day 0 and day 4 (n = 283); group 2 recipients with a high panel of reactive antibody (PRA > 20%) and retransplant patients received rATG for induction (n = 129) for a maximum of 2 weeks postoperatively. The incidence of rejection was 14.5% for group 1 vs. 8.5% for group 2 patients. To avoid confounding variable associated with the rejection treatment, any patient with rejection was excluded for statistical analysis, as were patients with follow- up less than 30 days. The final study group for analysis included 350 patients: 235 with Basiliximab induction (group 1) and 115 rATG induction (group 2). The mean follow-up was 21.8 +/- 11 months. Differences in the incidences of postoperative hernia, wound infections, or lymphoceles requiring any form of drainage were analyzed for statistical significance using the chi-square test. RESULTS: The percentage of patients with wound complications was 26.0% versus 39.1% (P < .025) for group 1 versus group 2, respectively. Incisional hernias occurred in 10.6% versus 18.3% patients (P < .05), wound infections in 11.1% versus 16.5% (P = NS), and lymphoceles in 10.6% versus 15.9% (P = NS) for the two groups, respectively. CONCLUSIONS: rATG-induced renal transplants recipients treated with sirolimus, cyclosporine, and steroids show a significantly increased incidence of postoperative incisional hernias and a trend toward a greater number of lymphocele and wound infection complications.

Adult↗
PubMed2005

Graft survival and immune regulation of pancreas allograft recipients induced with thymoglobulin, sirolimus, and cyclosporine.

BACKGROUND: Our objective was to determine the impact of thymoglobulin-sirolimus-cyclosporine immunosuppression on the alloimmune response of pancreas-kidney transplant recipients. METHODS: Thirty-six pancreas transplant recipients received an induction protocol of thymoglobulin, sirolimus, reduced-dose cyclosporine, and corticosteroids. A subset of 10 recipients were also enrolled in a study to measure immune responsiveness. Flow PRA-determined HLA antibody, donor-specific flow cytometry crossmatching (FCXM), T-cell subset, and suppressor cell assays were performed at various timepoints during the first posttransplant year. RESULTS: One-year patient, kidney, and pancreas survivals were 97%, 94%, and 92%, respectively. There was 1 death due to sepsis, and 1 kidney and 2 pancreas graft losses. There were no acute rejection episodes. Recipients in the immune-monitoring study displayed depression of CD3, CD4, and CD8 counts (<80%) until 3 months posttransplant. At transplantation, 9 of 10 patients displayed <10% class I HLA antibody. By 3 months, 7 of 10 showed a transient elevation in class I HLA antibodies, with 2 patients expressing >80% flow PRA. At transplant 1 patient was FCXM-positive, whereas, by 3 months posttransplant, 2 of 10 patients demonstrated a positive FCXM. There were no clinical consequences to either the presence of HLA antibody or the positive FCXMs. By 6 months, 7 of 9 patients expressed immunoregulatory suppressor cell activity. CONCLUSIONS: The absence of acute rejection events was likely due to inhibition of donor-specific immunity. Seventy percent of patients demonstrated an early non-donor-directed HLA antibody response that had no adverse effect on graft function and 78% of the patients displayed immunoregulatory suppressor cell function, probably contributing to the successful clinical outcome.

Anti-Bacterial Agents↗
PubMed2005

A pilot study of immunosuppression minimization after pancreas-kidney transplantation utilizing thymoglobulin induction and sirolimus maintenance therapy.

AIMS: To determine outcomes utilizing thymoglobulin and sirolimus immunosuppression, with early steroid withdrawal in low-immune responder pancreas-kidney (SPK) recipients, and conversion from cyclosporine (CsA) to mycophenolic acid (MPA) in all recipients at 6 months posttransplantation. METHODS: SPK recipients received thymoglobulin, sirolimus, and reduced-dose CsA immunosuppression. Low immune responders (non-African-Americans with a pretransplant PRA < 30%) were withdrawn from prednisone on posttransplant day 5 and high immune responders were continued on prednisone. All recipients were converted from CsA to MPA at 6 months posttransplantation. During conversion, recipient immune response was monitored by flow PRA and a T-cell stimulation assay (Cylex). RESULTS: With a mean follow-up of 9 +/- 4 months, one pancreas was lost to pancreatitis, with no patient or kidney losses and no acute rejection episodes. All eight low immune responder patients were steroid-free at 9 +/- 5 months posttransplantation. Seven patients (five low and two high immune responders) with at least 6-month follow-up were converted from CsA to MPA. One high immune responder with a pretransplant PRA of 43% remained with a PRA of 53% +/- 2% postconversion. The second high immune responder had a pretransplant PRA of 34% and a postconversion PRA of 0%. The five low immune responders had a mean pretransplant PRA of 16% +/- 15% and a postconversion PRA of 0% (P < .01). The Cylex assay resulted in 67% low responsiveness for both high and low immune responders. CONCLUSION: Thymoglobulin induction with sirolimus maintenance therapy permitted immunosuppression minimization in selected pancreas transplant recipients. Posttransplant evaluation revealed a diminished (regulated) immune response in six of seven patients.

Animals↗
PubMed2004

The effect of pancreas transplantation on peripheral vascular disease complications.

BACKGROUND: We sought to determine whether pancreas transplantation reduced the incidence of peripheral vascular complications in diabetics with renal insufficiency. METHODS: A retrospective single-center review was done of 36 kidney-pancreas (KP) and 88 kidney-alone (KA) recipients with a diagnosis of diabetes and end-stage renal disease (ESRD) transplanted between May 1997 and July 2002. Risk factors studied included type of transplant, age, gender, history of smoking, coronary artery disease, hypertension, and peripheral vascular disease (PVD). The endpoint was first peripheral vascular event occurring after transplantation, defined as either an amputation or revascularization procedure. RESULTS: The mean age of the cohort was 51 +/- 9 years, 64% of patients were of male gender, 20% with a history of smoking, 98% with hypertension, 15% with coronary artery disease (CAD), and 12% with a history of PVD. With a median follow-up of 45 months (12 to 79 months), 3/36 (8%) of KP recipients suffered a PVD complication, compared to 10/88 (11%) of KA recipients (P = NS). Similarly, age, gender, a past history of smoking, CAD, and hypertension were not predictive of PVD complications. Five of 15 patients (33%) with a pretransplant history of PVD suffered a postoperative PVD event compared to only 8 of 109 patients (7%) with no prior history of PVD (P =.008). CONCLUSIONS: Restoration of normoglycemia by pancreas transplantation did not reduce the risk of PVD complications in diabetics with renal failure. A pretransplant history of PVD was the only risk factor associated with posttransplant PVD events.

Adult↗
PubMed2001

Guillain-Barré syndrome after solid organ transplantation.

BACKGROUND: Neurological complications occur frequently in solid organ transplant recipients. However, the peripheral nerves are usually spared significant toxicity. Guillain Barré syndrome (GBS) is the most common cause of acute neuropathy in adults. Despite numerous reports of GBS in recipients of bone marrow transplants, GBS has rarely been reported in recipients of solid organ transplants. Recent evidence supports the role of the immune system in initiating and perpetuating the ongoing neural damage in this entity. Infectious agents may initiate the immune attack, and the association of GBS with cytomegalovirus (CMV) infection has been studied extensively. METHODS: To alert clinicians to the occurrence of GBS in the latter setting, we report five new cases of GBS after solid organ transplant and summarize five other cases previously reported in the literature. RESULTS: The GBS cases (published and unpublished) have much in common: all the patients were men, most had evidence of active CMV infection at or before the onset of GBS, and all but one developed GBS within 1 year after transplantation (range 1-26 months). CONCLUSION: The association of GBS with cytomegalovirus (CMV) infection in the nontransplant population and evidence of CMV infection in almost all reported cases of GBS in solid organ transplant recipients suggest that CMV may have a role in triggering this illness.

Adult↗
PubMed2000

Therapeutic drug monitoring of sirolimus: correlations with efficacy and toxicity.

UNLABELLED: We sought to examine the potential benefits of therapeutic drug monitoring of sirolimus, a potent immunosuppressive agent that displays a pleiotropic array of side effects. METHODS: A high-performance liquid chromatography (LC) procedure combined with ultraviolet detection (UV) was used to measure serial concentrations of parent compound sirolimus in 150 renal transplant recipients over a period of 4 yr. Drug concentrations in whole blood at trough time, as well as within pharmacokinetic profiles, were correlated with clinical events using contingency tables, logistic regression analysis, and receiver operating characteristic (ROC) curves. RESULTS: The LC/UV method showed an excellent correlation with detection of LC-resolved components by tandem mass spectrometry, demonstrating that the LC/UV method selectively detected parent compound. Sirolimus displayed the characteristics of a critical-dose drug: Its concentration could not be predicted by a standard body or demographic measure, or by dose, and it showed high degrees of intra- and inter-individual variability. However, there was a good correlation between trough and area-under-the-curve measurements. There was a significant association between trough values expressed as either observed ( < 5 ng/mL) or dose-corrected parameter ( < 1.7 ng/mL per mg administered drug) and the occurrence and severity of acute rejection episodes - despite the low overall incidence of 23 episodes among the cohort of 150 patients. Similarly, ROC functions showed a correlation of the occurrence of hypertriglyceridemia, thrombocytopenia, and leukopenia, but not hypercholesterolemia, with trough concentrations above 15 ng/mL. CONCLUSION: Due to its behavior as a critical-dose drug, therapeutic monitoring to measure sirolimus concentrations by a LC/UV method may provide clinicians with a tool to optimize outcomes.

Adolescent↗
PubMed1999

Flow cytometry-detected IgG is not a contraindication to renal transplantation: IgM may be beneficial to outcome.

BACKGROUND: At our transplant center, primary recipients of either a haplo-identical (haplo-ID) living related (LRD) or a cadaveric (CAD) donor renal allograft are transplanted after a negative donor-specific IgG anti-human globulin (AHG) cross-match (XM). Testing included the historically highest panel-reactive antibody and the immediate (0-7 days) pretransplant sera. A positive donor specific IgM-AHG XM has not been a contraindication to transplant. Reports suggest that donor-specific flow cytometry cross-matches (FCXM) may be more clinically informative than the AHG-XM. METHODS: We therefore evaluated the impact of a positive FCXM (IgG or IgM) on the rejection frequency (0-12 months after transplant) and 1-year graft survival for cyclosporine-prednisone-treated primary (haplo-ID and CAD) renal allograft recipients. All transplants were performed after a negative donor-specific IgG AHG-XM regardless of the IgM-AHG XM status. RESULTS: Rejection frequencies (26% vs. 31%, P = NS) and 1-year graft survivals (92% vs. 89%, P = NS) were comparable for haplo-ID LRD FCXM-negative and IgG-FCXM-positive recipients. However, IgM-FCXM-positive LRD recipients experienced significantly fewer rejections (13% vs. 26% P<0.02) and an improved 1-year graft survival (100% vs. 92%, P<0.02) than FCXM-negative LRD recipients. Similar results were observed for primary CAD recipients. Rejection frequencies (40% vs. 44%, P = NS) and 1-year graft survivals (83% vs. 81%, P = NS) were comparable for primary CAD FCXM-negative and IgG-FCXM-positive recipients. Again, IgM-FCXM-positive primary CAD recipients experienced significantly fewer rejections (22% vs. 40%, P<0.02) and improved 1-year graft survivals (89% vs. 83%, P<0.05) than FCXM-negative recipients. CONCLUSION: These data suggest that, after a negative donor-specific IgG-AHG XM, an IgG-positive FCXM is not a contraindication to transplantation. The presence of IgM may be beneficial in reducing the occurrence of rejection episodes and improving graft survivals.

Contraindications↗
PubMed1999

A phase I study of a 4-week course of SDZ-RAD (RAD) quiescent cyclosporine-prednisone-treated renal transplant recipients.

BACKGROUND AND METHODS: This phase I, randomized, blinded, placebo-controlled study assessed the safety profile and pharmacokinetics of a 4-week course of once-daily, sequential ascending doses (0.75, 2.5, or 7.5 mg/day) of SDZ-RAD (RAD) capsules in renal transplant recipients on a stable regimen of cyclosporine (CsA; Neoral) and prednisone. RESULTS: RAD displayed a similar spectrum of side effects as observed with rapamycin, namely, an increased incidence of infection associated with the augmented immunosuppression and a dose-related occurrence of thrombocytopenia, hypercholesterolemia, and hypertriglyceridemia, particularly at the 7.5-mg dose. The pharmacokinetic parameters of RAD showed dose proportionality, a good correlation between trough and area under the curve (AUC) concentrations, and a moderate accumulation of 2.5-fold. The drug was absorbed within 2 hr and displayed a 16-19-hr half-life, which is shorter than that of rapamycin. RAD reached steady state at 4 days. Preliminary kinetic-dynamic correlations indicate a correlation between thrombocytopenia (but not hyperlipidemia) and AUC, as well as maximum drug concentrations, and weight-adjusted dose. At the end of a 4-week course of simultaneous dosing, there was no evidence of a pharmacokinetic interaction between CsA and RAD. CONCLUSION: This study suggests that the shorter half-life of RAD compared to rapamycin may confer the benefits of rapid attainment of steady state and dissipation of effects upon drug cessation. Controlled, multicenter trials are being planned to assess the impact of these features on clinical outcomes.

Adult↗
PubMed1999

Program development and routine notification in a large, independent OPO: a 12-year review.

Since its inception 12 years ago, a large, independent OPO experienced a 631% growth in the number of organ donors. These increases in organ recovery were achieved initially through successful mergers, and later, following the mergers, through focused management, OPO organizational development, and hospital marketing and system development. The cumulative percentage increases beginning in 1987 resulted in the OPO achieving 27.2 donors per million population. In 1996 a system of routine notification of all hospital deaths was implemented and a 24-hour communications center was operated. After 3 full years of routine notification, 73% of all deaths were called to the OPO, resulting in the following increases: total referrals, 691%; organ referrals, 41%; organ donors, 16%; bone donors, 149%; skin donors, 123%; and heart valve donors, 78%. The 16% increase in organ donors was twice the national growth rate and significantly more than the 2% growth experienced by the OPO in the year preceding the implementation of routine notification. The OPO has demonstrated sustained growth over the past decade in a time when erosion of donor recovery levels is always a possibility and frequently a reality for many OPOs.

Humans↗
PubMed1998

Can an immunologically, nonreactive potential allograft recipient undergo transplantation without a donor-specific crossmatch?

Performance of the pretransplant crossmatch requires 4 or more hours . Delays in the crossmatch might alter operating room availability and thereby increase donor organ cold ischemia time that might then result in increased risk of delayed graft function. To avoid these problems, recipients could be identified who would be expected to display negative donor crossmatches and who could be transplanted with a concurrent or retrospective rather than a pretransplant crossmatch. We, therefore, evaluated the percent reactive antibodies and donor IgG-antihuman globulin (AHG) crossmatch results of 1165 sera from 220 potential allograft recipients. Twenty-five (11%) of 220 recipients consistently displayed a 0% PRA and, with only one exception, their sera (n= 156) tested IgG-AHG crossmatch-negative against potential cadaveric donors (a 0.6% IgG-AHG positive crossmatch risk). These data suggest that the timing of the pretransplant serum crossmatch could be altered for a highly selected group of immunologically nonreactive recipients.

Female↗
PubMed1998

Immunosuppressive effects and safety of a sirolimus/cyclosporine combination regimen for renal transplantation.

BACKGROUND: Sirolimus, a novel immunosuppressant that inhibits cytokine-driven cell proliferation and maturation, prolongs allograft survival in animal models. After a phase I trial in stable renal transplant recipients documented that cyclosporine and sirolimus have few overlapping toxicities, we conducted an open-label, single-center, phase I/II dose-escalation trial to examine the safety and efficacy of this drug combination. METHODS: Forty mismatched living-donor renal transplant recipients were sequentially assigned to receive escalating initial doses of sirolimus (0.5-7.0 mg/m2/day), in addition to courses of prednisone and a concentration-controlled regimen of cyclosporine. We conducted surveillance for drug-induced side effects among sirolimus-treated patients and compared their incidence of acute rejection episodes as well as mean laboratory values with those of a historical cohort of 65 consecutive, immediately precedent, demographically similar recipients treated with the same concentration-controlled regimen of cyclosporine and tapering doses of prednisone. RESULTS: The addition of sirolimus reduced the overall incidence of acute allograft rejection episodes to 7.5% from 32% in the immediately precedent cyclosporine/prednisone-treated patients. At 18- to 47-month follow-up periods, both treatment groups displayed similar rates of patient and graft survival, as well as morbid complications. Although sirolimus-treated patients displayed comparatively lower platelet and white blood cell counts and higher levels of serum cholesterol and triglycerides, sirolimus did not augment the nephrotoxic or hypertensive proclivities of cyclosporine. The degree of change in the laboratory values was more directly associated with whole blood trough drug concentrations than with doses of sirolimus. CONCLUSIONS: Sirolimus potentiates the immunosuppressive effects of a cyclosporine-based regimen by reducing the rate of acute rejection episodes.

Adult↗
PubMed1998

Impact of early cyclosporin average blood concentration on early kidney transplant failure.

This retrospective study served to examine the correlation between the degree of cyclosporin (CyA) exposure, as estimated by a single pharmacokinetic (PK) profile performed at 1 week post-transplant, and the outcome of 290 consecutive renal transplants performed over a 6-year period. For this retrospective analysis patients were stratified into four historical groups based on 12-versus 24-h PK studies and on the use of radioimmunoassay versus fluorescence polarization immunoassay methods for estimates of CyA concentrations. Four PK measures-trough concentration (C0), average concentration values (Cav; i.e., the dosing interval-corrected area under the concentration-time curve), maximum concentration (Cmax), and time to maximum concentration (tmax)-were examined as predictors of patient, graft, and rejection-free survival rates for each of the four groups individually and for all groups combined. Patients with an initial Cav > or = 550 ng/ml had higher 1-year (88%) and 6-year (66%) graft survival rates than patients with Cav < 550 ng/ml, who had 1- and 6-year graft survival rates of 80% and 59%, respectively (P = NS). Statistically significant differences were observed in graft survival rates between patients with Cav < 550 versus Cav > or = 550 ng/ml at 30 (88% vs 96%; P < 0.02), 60 (85% vs 94%; P < 0.007), 90 (85% vs 94%; P < 0.02), and 180 (83% vs 92%; P < 0.05) days. Moreover, patients with Cav < 550 ng/ml displayed more severe rejection episodes, as judged by Banff classification, than patients who displayed Cav > or = 550 ng/ml (grades II and III; 71% vs 50%; P = 0.036). In contrast, the C0, Cmax and tmax values did not correlate with patient, graft, or rejection-free survival rates. The pharmacokinetic parameter of Cav correlated strongly with early graft survival and may therefore, be a useful predictor of those renal transplant patients who may require more intensive post-transplant monitoring of CyA concentrations by serial PK studies to improve graft survival.

Adult↗
PubMed1998

The metabolic effects of enterally administered ribonucleic acids.

Roles for dietary sources of preformed purines and pyrimidines such as RNA in various systems have been demonstrated in recent years. These include maintenance of a competent immune system, gut development, hepatic function and many others, with a central theme of rapidly dividing cells requiring these compounds for optimal function. These compounds were previously thought to be non-essential but are now considered to be conditionally required when various stresses, including rapid growth and infection, are present. A number of recent studies are summarized that cover a variety of areas and are consistent with critical roles for dietary sources of nucleotides for many cellular functions.

Adolescent↗