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Biomedical subjects

Colm Magee

Publications and source records attributed to Colm Magee.

8 recordsLinked to original sources
PubMed2005

Sirolimus and thrombotic microangiopathy after allogeneic hematopoietic stem cell transplantation.

Thrombotic microangiopathy (TMA) may occur after allogeneic hematopoietic stem cell transplantation (HSCT) and is related in part to calcineurin inhibitor toxicity. We observed a higher-than-expected rate of TMA when calcineurin inhibitors were combined with sirolimus. To determine the incidence of and risk factors for TMA after HSCT, we performed a retrospective cohort analysis of myeloablative allogeneic HSCT recipients between 1997 and 2003. TMA diagnosis required the simultaneous occurrence of (1) creatinine increase >2 mg/dL or >50% above baseline, (2) schistocytosis, (3) increased lactate dehydrogenase, and (4) no evidence of disseminated intravascular coagulopathy. A total of 111 sirolimus-exposed subjects were compared with 216 nonexposed subjects after HSCT. TMA occurred in 10.8% of the sirolimus group and 4.2% in the nonsirolimus group (odds ratio, 2.79; P=.03). Sirolimus exposure was associated with TMA earlier than in nonsirolimus patients (25 versus 58 days; P=.04). Only the use of sirolimus (exact odds ratio, 3.49; P=.02) and grade II to IV acute graft-versus-host disease (exact odds ratio, 6.60; P=.0002) were associated with TMA in regression analyses. Treatment of TMA varied among affected individuals. Renal recovery was complete in 92% of sirolimus-treated patients. Overall survival after TMA diagnosis was better for sirolimus subjects than for nonsirolimus subjects (58.3% versus 11.1%; P=.02). Sirolimus seems to potentiate the effects of calcineurin inhibitors on TMA after HSCT. TMA associated with sirolimus seems reversible and has a favorable prognosis when compared with TMA associated with calcineurin inhibitors alone. A careful monitoring strategy for TMA should be used with a sirolimus-containing graft-versus-host disease prophylaxis regimen.

Adolescent↗
PubMed2004

TNP-470, an angiogenesis inhibitor, attenuates the development of allograft vasculopathy.

Fischer 344 rat recipients of Lewis allografts were treated with TNP-470, a synthetic fumagillin derivative and a well-established angiogenesis inhibitor. TNP-470 alone resulted in some prolongation of graft survival as compared with untreated recipients, but all grafts ultimately failed. In contrast, treatment with cyclosporine (CsA) from day 0 to 30 resulted in prolonged graft survival and marked cardiac allograft vasculopathy (CAV) by histology (mean score 2.28+/-0.2). There were many neovessels within the intima of CAV lesions. When TNP-470 was administered in combination with CsA from day 0 to 30, the degree of CAV was similar to that with CsA alone (mean score 2.22+/-0.26). However, when TNP-470 was administered from day 30 to 120 after discontinuation of CsA, there was a marked reduction in the degree of CAV (mean score 1.08+/-0.11). Therefore, TNP-470 interrupts the progression of CAV when given late but does not prevent its development when given immediately posttransplantation.

Abdomen↗
PubMed2003

A prospective, randomized, clinical trial of intraoperative versus postoperative Thymoglobulin in adult cadaveric renal transplant recipients.

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.

Acute Disease↗
PubMedDate not supplied

Low molecular weight heparins in renal failure.

Low molecular weight heparins are now commonly used for systemic anticoagulation. Although elimination is mainly by the renal route, these drugs are being prescribed to patients who are dialysis dependent or have renal failure. We report 3 cases where the use of these drugs in patients with severe renal failure significantly prolonged anti-Xa activity and serious bleeding complications occurred. Concomitant prescription of other anti-thrombotic drugs may have contributed to the bleeding in 2 cases. These cases emphasize the potential toxicity of low molecular weight heparins in patients with severe renal failure and that these drugs should be used with great caution in such patients. If prescribed, doses should be lowered and anti-Xa activity frequently measured. The use of other anti-thrombotic drugs should be minimized.

Adult↗