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John C Magee

Publications and source records attributed to John C Magee.

At least 19 recordsLinked to original sources
PubMed2007

12-month safety and efficacy of everolimus with reduced exposure cyclosporine in de novo renal transplant recipients.

The proliferation signal inhibitor everolimus (Certican), has demonstrated efficacy with full-dose cyclosporine (CsA) (Neoral). Two multicenter randomized controlled studies were performed to compare 12-month efficacy and safety of everolimus 1.5 and 3.0 mg/day with reduced-dose CsA. Study 1 enrolled 237 de novo renal allograft recipients, randomizing 222 nonblack patients to either everolimus 1.5 or 3.0 mg/day, with the Neoral) dose guided by C(2) (monitoring of CsA concentration 2 h after dosing). Study 2 had a similar protocol, with basiliximab included, enrolling 256 recipients and randomizing 243 nonblack patients. In Study 1, there was a lower incidence of acute rejection in nonblack patients on 3 mg/day (16.4%) compared with 1.5 mg/day (25.9%), P = 0.08. In Study 2, the inclusion of basiliximab lowered the overall incidence of acute rejection; 14.3% of nonblack patients (3 mg/day) and 13.6% of nonblack patients (1.5 mg/day) had acute rejection by 12 months (P =0.891). Renal function was preserved throughout the study, with no differences observed between groups within studies. Everolimus was well tolerated with no significant differences between doses. Everolimus, in combination with reduced-dose Neoral), demonstrated efficacy and was well tolerated. Basiliximab allows for utilization of lower doses of everolimus with reduced dosing of Neoral).

Adult↗
PubMed2006

Early pancreas transplant outcomes with histidine-tryptophan-ketoglutarate preservation: a multicenter study.

Little is known about the use of histidine-tryptophan-ketoglutarate (HTK) preservation solution for pancreas preservation. We compared early pancreas graft outcomes at four pancreas transplant programs within the state of Michigan in 2002 and 2003 (University of Wisconsin [UW] era) with those in 2004 (HTK era). The primary endpoint was early graft loss. The UW group (n=41) and the HTK group (n=36) had similar outcomes with respect to: technical graft loss (9.8% vs. 8.3%, P=NS), 90-day graft function (90.2% vs. 86.1%, P=NS), and rate of pancreatic leak/abscess (12.2% vs. 11.1%, P=NS). There were also no significant differences in postoperative amylase and lipase levels between the two groups. The HTK group did have significantly more acute rejection within the first 180 days (25.0% vs. 9.8%, P<0.05). HTK is a suitable substitute for UW in the preservation of pancreas allografts.

Adult↗
PubMed2005

Vancomycin-resistant enterococcal colonization and infection in liver transplant candidates and recipients: a prospective surveillance study.

BACKGROUND: Vancomycin-resistant enterococcal (VRE) infections cause significant morbidity and mortality among patients undergoing liver transplantation. We performed a prospective study among patients awaiting transplantation to assess rates, risk factors, and outcomes associated with VRE colonization before and after transplantation. METHODS: All adults on the transplantation waiting list from 2000-2003 were eligible. Demographic, historical, and laboratory data, as well as stool samples to be analyzed for VRE, were collected at enrollment and every 4-6 months thereafter until transplantation. After transplantation, samples were obtained every 3 days during hospitalization and were analyzed for VRE; outcomes were assessed at 90 days. RESULTS: Overall, 375 patients were enrolled in our study, and 142 received transplants. VRE colonization occurred in 50 (13%) of 375 patients before transplantation and was independently associated with treatment with antianaerobic antimicrobials, third-generation cephalosporins, proton pump inhibitors, or neomycin; having a recent endoscopic retrograde cholangiopancreatogram or paracentesis procedure; and admission to the liver unit. Of these 50 patients, 22 (44%) received a transplant, and 7 (32%) of 22 developed a VRE infection after transplantation. An additional 22 patients (18%) who were not colonized before transplantation acquired VRE after transplantation; VRE infection developed in 5 (23%) of these patients. Patients colonized with VRE either before or after transplantation had longer stays in the intensive care unit and the hospital. Mortality at 90 days was significantly greater among those who acquired VRE after transplantation (5 [23%] of 22), compared with those who had VRE colonization before transplantation (2 [9%] of 22). CONCLUSIONS: Liver transplantation candidates with VRE colonization before transplantation experience greater morbidity but not greater mortality, compared with noncolonized candidates. Transplant recipients who acquire VRE after transplantation have a higher mortality rate than noncolonized recipients. Strategies should be implemented to reduce nosocomial VRE acquisition after transplantation among this vulnerable group.

Adult↗
PubMed2005

Graft rejection mediated by CD4+ T cells via indirect recognition of alloantigen is associated with a dominant Th2 response.

CD4(+) T cells that respond to indirectly presented alloantigen have been shown to mediate chronic rejection, however, the role of the indirect pathway in acute rejection has yet to be completely elucidated. To this end, BALB/c or C57BL/6 mice were depleted of CD8(+) T cells and transplanted with class II transactivator (CIITA)-deficient cardiac allografts, which cannot directly present class II alloantigens to CD4(+) T cells. In this manner, the rejection response by CD4(+) cells was forced to rely upon the indirect recognition pathway. When not depleted of CD8(+) cells, both BALB/c and C57BL/6 mice rejected CIITA-/- allografts and a polarized Th1 response was observed. In contrast, when BALB/c recipients of CIITA-/- allografts were depleted of CD8(+) T cells, the grafts were acutely rejected and a strong Th2 response characterized by eosinophil influx into the graft was observed. Interestingly, CD8-depleted C57BL/6 recipients of CIITA-/- allografts did not acutely reject their transplants and a Th2 response was not mounted. These findings indicate that CD4(+) T cells responding to indirectly presented alloantigens mediate graft rejection in a Th2-dominant manner, and provide further evidence for the role of Th2 responses in acute graft rejection.

Animals↗
PubMed2005

Biliary atresia: clinical profiles, risk factors, and outcomes of 755 patients listed for liver transplantation.

OBJECTIVES: To test the hypothesis that risk analysis from the time of listing for liver transplantation (LT) focuses attention on areas where outcomes can be improved. STUDY DESIGN: Competing outcomes and multivariate models were used to determine significant risk factors for pretransplantation and posttransplantation mortality and graft failure in patients with biliary atresia (BA) listed for LT and enrolled in the Studies of Pediatric Liver Transplantation (SPLIT) registry. RESULTS: Of 755 patients, most were infants (age < 1 year). Significant waiting list mortality risk factors included infancy and pediatric end-stage liver disease (PELD) score > or = 20, whose components were also continuous risk factors. Survival posttransplantation (n=567) was 88% at 3 years. Most deaths were from infection (37%). Posttransplantation mortality risk factors included infant recipients, height/weight < -2 standard deviations (SD), use of cyclosporine versus tacrolimus and retransplantation. Graft failure risks included height/weight < -2 SD, cadaveric partial donors, donor age < or = 5 months, use of cyclosporine versus tacrolimus, and rejection. CONCLUSIONS: Referral for LT should be anticipatory for infants with BA with failed portoenterostomies. Failing nutrition should prompt aggressive support. Post-LT risk factors are mainly nonsurgical, including nutrition, the relative risk of infection over rejection, and the choice of immunosuppression.

Biliary Atresia↗
PubMed2005

Extracorporeal support for organ donation after cardiac death effectively expands the donor pool.

BACKGROUND: We sought to evaluate the effect on short-term outcomes of normothermic, extracorporeal perfusion (ECMO) for donation of abdominal organs for transplantation after cardiac death (DCD). Study parameters included increase in number of donors and organs, types of organs procured, and viability of kidneys transplanted. METHODS: We retrospectively reviewed medical record data for all patients enrolled in our ECMO-supported DCD donor protocol between 10/1/2000 to 2/01/2004. We also reviewed the records for all patients undergoing organ donation after brain-death (DBD) during the study period at our institution. Recipient data were obtained and analyzed for all kidneys procured from both groups. RESULTS: Twenty patients were enrolled in our DCD protocol and underwent attempted organ donation. Fifteen patients completed the protocol; 3 maintained cardiac function throughout the prescribed 60 minutes after withdrawal of life support, and two patients' organs were deemed unsuitable for transplantation. Fourteen (70%) of the DCD donor patients originated on the trauma service and six (30%) were from other clinical services. The DCD program increased the potential donor pool by 33% (61 versus 81 patients) and the number of kidneys transplanted by 24% (100 versus 124). A total of 24 kidney, 5 liver, and 1 pancreas transplants were performed with these organs. Two of 24 (8.3%) DCD kidneys had delayed graft function. There were no perioperative rejection episodes or deaths. CONCLUSION: The implementation of a DCD protocol using extracorporeal perfusion increased the potential organ donor pool at our institution by 33%. This was accomplished without short term adverse effect on organ function compared with kidneys transplanted from DBD donors.

Adolescent↗
PubMed2005

Organ donation and utilization in the United States, 2004.

This article discusses issues directly related to the organ donation process, including donor consent, donor medical suitability, non-recovery of organs, organs recovered but not transplanted, expanded criteria donors (ECD), and donation after cardiac death (DCD). The findings and topics covered have important implications for how to evaluate and share best practices of organ donation as implemented by organ procurement organizations (OPOs) and major donor hospitals in the same donation service areas (DSAs). In 2002 and 2003, US hospitals referred more than one million deaths or imminent deaths to the OPOs of their DSA. Referrals increased by nearly 10% from 2002 to 2003 (1,022,280 to 1,121,392). Donor consents have increased by about 5% and the number of total deceased donors has risen from 6,187 to 6,455. Since multiple organs are recovered from most donors, this increase allowed more than 500 additional wait-listed candidates to receive an organ transplant than in the prior year. Non-traditional donor sources have experienced a large rate of increase; in 2003 the number of ECD kidney donors increased by 8% and the number of DCD donors increased by 43%, from 189 donors in year 2002 to 271 donors in 2003.

Ethnicity↗
PubMed2004

Single-center study of technical graft loss in 714 consecutive renal transplants.

No series has specifically focused on rates of technical failure in the kidney transplantation operation. We retrospectively examined the incidence of technical graft loss in a single kidney transplant program. A total of 714 transplants were performed, with a mean follow-up of 3.4 years (range 2-5 years). Technical graft loss was defined as graft loss within the first 2 weeks, without evidence of allograft rejection. Fourteen patients (2%) demonstrated technical graft loss, none of whom received kidneys with multiple renal arteries (n = 106 with multiple renal arteries). The incidence of technical graft loss was significantly higher in diabetic recipients (4.3% vs. 1.4%, P = 0.03). The mean donor age was significantly higher (46.7 vs. 38.1 years, P = 0.05) in patients with technical graft loss. We observed that arterial thrombosis seemed to be related to the donor (older donor significant risk P = 0.04) and that venous thrombosis seemed to be related to the recipient (four of seven patients with positive hypercoagulable workup).

Adolescent↗
PubMed2004

Long-term follow-up of percutaneous transhepatic balloon cholangioplasty in the management of biliary strictures after liver transplantation.

BACKGROUND: This study evaluated the efficacy of a protocol of initial balloon dilation for biliary strictures after liver transplantation. METHODS: Complete records from 96 patients with biliary strictures were retrospectively reviewed. Seventy-six patients received percutaneous transhepatic balloon cholangioplasty (PTBC) after initial placement of biliary drainage (percutaneous transluminal cholangiography [PTC]) tube. In most cases, three dilations were performed with a 4 to 8 week interval between procedures. Follow-up ranged from 6 months to 10 years. RESULTS: PTBC successfully treated strictures in 39 of 76 (51.3%) cases. Factors favoring successful PTBC included older age at transplant, shorter cold ischemic time, and single strictures. There were nine recurrent strictures after PTBC, all of which were successfully treated by nonoperative measures. The number of dilations performed affected both the likelihood of success and the long-term risk of stricture recurrence. Of the 37 PTBC failures, 14 underwent subsequent surgical revision. When both angiographic and surgical modalities were considered, treatment success was associated with first transplants, shorter cold ischemic time and operative time, and less intraoperative transfusion requirements. Factors associated with treatment failure included multiple, central hepatic duct, and intrahepatic strictures. PTC-tube independence was achieved in 51 of 76 (67%) patients using the combined approach of PTBC and surgery for PTBC failures. CONCLUSIONS: PTBC is an effective initial modality for treating posttransplant biliary strictures. Prolonged cold ischemic and operative times and multiple or peripheral strictures predispose to treatment failure. Solitary extrahepatic strictures that fail PTBC are salvageable with surgical revision with excellent results.

Adult↗
PubMed2004

Ex vivo ureteroscopic treatment of calculi in donor kidneys at renal transplantation.

PURPOSE: We evaluated the safety and efficacy of ex vivo ureteroscopy (ExURS) as a means of rendering the donated kidney stone-free at live donor renal transplantation. MATERIALS AND METHODS: A total of 10 suitable kidney donors with small, unilateral nonobstructive calculi underwent live donor nephrectomy (8 open flank, 2 hand assisted transperitoneal). Immediately after cold perfusion, ExURS was performed in an iced saline solution. Access to the collecting system was via the ureteral stump. Calculi were either removed with endoscopic baskets and/or completely fragmented with Holmium laser lithotripsy. RESULTS: Access to the renal collecting system was technically successful in all cases. A total of 10 stones, ranging in largest diameter from 1 to 8 mm (average 5.2) were visualized. Of the kidneys 6 had solitary stones, 2 had 2 stones and 1 had no stone. Of 10 stones 9 were successfully removed and/or fragmented with an average procedure time of 6.5 minutes (range 3 to 28). Indwelling ureteral stents were placed at transplantation in 5 of 10 kidneys. There were no intra-operative or postoperative ureteral complications. At 1 month after transplant serum creatinine ranged from 0.9 to 2.7 mg/dl (average 1.5). At a mean followup of 33.2 months new stones have not formed in any recipients and at mean 36.4-month followup no new calculi have formed in the remaining kidney of any donors. CONCLUSIONS: ExURS is a technically feasible means of rendering a stone bearing kidney stone-free without compromising ureteral integrity or renal allograft function.

Adolescent↗
PubMed2004

Successful renal transplantation following prior bone marrow transplantation in pediatric patients.

Improving survival rates following pediatric bone marrow transplantation (BMT) will likely result in greater numbers of children progressing to end-stage renal disease (ESRD) because of prior chemotherapy, irradiation, sepsis, and exposure to nephrotoxic agents. Renal transplantation remains the treatment of choice for ESRD; however, the safety of renal transplantation in this unique population is not well established. We report our experience with living related renal transplantation in three pediatric patients with ESRD following prior BMT. Two patients with neuroblastoma and ESRD because of BMT nephropathy, and one patient with Schimke immuno-osseous dysplasia and ESRD because of immune complex mediated glomerulonephritis and nephrotic syndrome. Age at time of BMT ranged from 2 to 7 yr. All patients had stable bone marrow function prior to renal transplantation. Age at renal transplant ranged from 8 to 14 yr. All three patients have been managed with conventional immunosuppression, as no patient received a kidney and BMT from the same donor source. These patients are currently 7 months to 6 yr status post-living related transplant. All have functioning bone marrow and kidney transplants, with serum creatinine levels ranging 0.6-1.2 mg/dL. There have been no episodes of rejection. One patient with a history of grade III skin and grade IV gastrointestinal-graft-vs.-host disease (GI-GVHD) prior to transplantation, had a mild flare of GI-GVHD (grade I) post-renal transplant and is currently asymptomatic. The incidence of opportunistic infection has been comparable with our pediatric renal transplant population without prior BMT. One patient was treated for basal cell carcinoma via wide local excision. Renal transplantation is an excellent option for the treatment of pediatric patients with ESRD following BMT. Short-term results in this small population show promising patient and graft survival, however long-term follow-up is needed. Pre-existing immune system impairment and bone marrow function should be taken into consideration when weighing different immunosuppressive agents for renal transplantation. Patients who have undergone renal transplantation following BMT are at high risk for opportunistic infections and malignancy, and need life-long medical surveillance.

Adolescent↗
PubMed2004

Everolimus with optimized cyclosporine dosing in renal transplant recipients: 6-month safety and efficacy results of two randomized studies.

Two prospective, randomized studies evaluated everolimus 1.5 vs. 3 mg/day with steroids and low-exposure cyclosporine (CsA) (C2 monitoring) in de novo renal transplant patients. Everolimus dosing was adjusted to maintain a minimum trough level of 3 ng/mL. Study 1 (A2306; n=237) had no induction therapy; in Study 2 (A2307; n=256) basiliximab was administered (Days 0 and 4). The primary endpoint was renal function at 6 months. CsA C2 target levels, initially 1200 ng/mL in Study 1 and 600 ng/mL in Study 2, were tapered over time post-transplant. Median creatinine levels in Study 1 were 133 and 132 micromol/L at 6 months in the 1.5 and 3 mg/day groups, respectively, and 130 micromol/L in both groups in Study 2. Biopsy-proven acute rejection (BPAR) occurred in 25.0% and 15.2% of patients in the 1.5 and 3 mg/day groups in Study 1, and 13.7% and 15.1% in Study 2. Incidence of BPAR was significantly higher in patients with an everolimus trough <3 ng/mL. There were no significant between-group differences in the composite endpoint of BPAR, graft loss or death, nor any significant between-group differences in adverse events in either study. Concentration-controlled everolimus with low-exposure CsA provided effective protection against rejection with good renal function.

Adult↗
PubMed2004

Pediatric transplantation.

Analysis of the OPTN/SRTR database demonstrates that, in 2002, pediatric recipients accounted for 7% of all recipients, while pediatric individuals accounted for 14% of deceased organ donors. For children fortunate enough to receive a transplant, there has been continued improvement in outcomes following all forms of transplantation. Current 1-year graft survival is generally excellent, with survival rates following transplantation in many cases equaling or exceeding those of all other recipients. In renal transplantation, despite excellent early graft survival, there is evidence that long-term graft survival for adolescent recipients is well below that of other recipients. A causative role for noncompliance is possible. While the significant improvements in graft and patient survival are laudable, waiting list mortality remains excessive. Pediatric candidates awaiting liver, intestine, and thoracic transplantation face mortality rates generally greater than those of their adult counterparts. This finding is particularly pronounced in patients aged 5 years and younger. While mortality awaiting transplantation is an important consideration in refining organ allocation strategies, it is important to realize that other issues, in addition to mortality, are critical for children. Consideration of the impact of end-stage organ disease on growth and development is often equally important, both while awaiting and after transplantation.

Age Distribution↗
PubMed2004

Kidney transplantation from organ donors following cardiopulmonary death using extracorporeal membrane oxygenation support.

Extracorporeal membrane oxygenation (ECMO) has the ability to provide normal organ perfusion and oxygenation in the absence of cardiac function and thus has the potential to improve viability of subsequently transplanted kidneys. In addition, ECMO support allows the donation following cardiopulmonary death (DCD) process to occur in a controlled manner that is acceptable to staff unfamiliar with DCD. In 1999 our center implemented a controlled DCD program that incorporates post-mortem ECMO support of the organs. Arterial and venous cannulae are placed following consent to donate, but prior to withdrawal of support. ECMO circulation is initiated immediately following declaration of death. Following a brief period where the donor family is allowed to grieve, the donor is moved to the operating room where organ recovery occurs. We reviewed the results of 20 kidney transplants from 13 ECMO supported donors that occurred between October 2000 and August 2003. One renal allograft was lost due to surgical complications, all 19 remaining grafts functioned. An 11% (2/19) delayed graft function rate was observed. Kidneys donated from "controlled" ECMO supported CPD donors are a viable source of organs for renal transplantation. This recovery method warrants further investigation.

Cadaver↗
PubMed2003

Limitations of EBV-PCR monitoring to detect EBV associated post-transplant lymphoproliferative disorder.

Post-transplant lymphoproliferative disorder (PTLD) represents a significant threat to the survival of pediatric transplant recipients. Epstein-Barr (EBV) viral load monitoring using polymerase chain reaction (PCR) has been reported to have a variable sensitively with relatively higher specificity as in an indicator of the development of PTLD. We report two cases of pathologically confirmed PTLD in children who failed to develop sustained increases in their EBV-PCR determined viral loads. We suggest that clinicians should be aware of the potential for false-negative results of EBV-PCR in pediatric transplant recipients.

Child↗