Biomedical subjects

S L Olsen

Publications and source records attributed to S L Olsen.

60 records · Page 4Linked to original sources

PubMedDate not supplied

Vascular rejection and its relationship to allograft coronary artery disease.

We have prospectively monitored 268 patients by our previously described method of routine immunofluorescence of endomyocardial biopsy specimens. We have classified these patients according to their rejection pattern: cellular, vascular, and mixed. The criteria for these designations have been previously described. In this study we retrospectively reviewed coronary angiograms of these patients to assess the presence and time-course of developing allograft coronary artery disease. All available explanted hearts and postmortem hearts were also assessed by light microscopic examination for acute coronary vasculitis and allograft coronary artery disease and by immunofluorescent microscopy for vascular immune complex deposition in a manner identical to immunofluorescent microscopic examination of endomyocardial biopsy specimens. Patients were also monitored for sensitization to immunoprophylactically administered murine monoclonal CD3 antibody (OKT3) and those demonstrated to be sensitized were separately analyzed. Clinical features and treatment of patients were retrospectively reviewed. We found that 141 patients could be classified as having cellular rejection, 76 as having vascular rejection, and 52 as having a mixed rejection pattern. The allograft survival in vascular rejection patients was significantly worse than in allografts of patients with cellular or mixed rejection, confirming our earlier results. Most importantly, we found a significant difference in the time to the development of allograft coronary artery disease based on the rejection pattern. This difference existed whether or not patients sensitized to OKT3 were excluded from evaluation. Patients with mixed rejection had an intermediate time to the development of allograft coronary artery disease between that of patients with cellular and vascular rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗

PubMedDate not supplied

Methotrexate therapy in pediatric heart transplantation as treatment of recurrent mild to moderate acute cellular rejection.

We have used adjunctive therapy with methotrexate as treatment of recurrent mild-to-moderate acute cellular rejection and in an attempt to reduce rejection frequency and corticosteroid dosage. The purpose of this study was to review our experience with this treatment strategy. Eight patients, 13.1 +/- 1.1 years of age (mean +/- standard error of the mean) at the time of transplantation, were given methotrexate in addition to their standard triple therapy immunosuppression. Methotrexate was started at 6.2 +/- 2 months after transplantation after an average of 3.1 +/- 0.4 rejection episodes. Patients were given methotrexate weekly for 8 weeks at 2.5 or 5 mg orally every 12 hours for three doses (0.23 +/- 0.02 mg/kg/week). The time to resolution of rejection was 17.9 +/- 4 days after initiating methotrexate therapy. The number of rejections per month decreased significantly from the 2 months before methotrexate therapy (1.49 +/- 0.1) when compared with both the 2 months during methotrexate therapy (0.50 +/- 0.1) and the 2 months after methotrexate therapy was completed (0.44 +/- 0.3) (p < 0.005). Furthermore, when comparing total rejection frequency since transplantation and before methotrexate therapy to a follow-up period of 21.8 +/- 5 months after completion of methotrexate therapy, the rejection frequency was significantly less (0.81 +/- 0.2 versus 0.10 +/- 0.06 rejections/month) (p < 0.01). Prednisone dosage was also significantly less when comparing the time before methotrexate therapy to immediately after completion of methotrexate therapy (0.23 +/- 0.04 versus 0.15 +/- 0.03 mg/kg/day) (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMedDate not supplied

Mycophenolate mofetil (RS-61443): preclinical, clinical, and three-year experience in heart transplantation.

Mycophenolate mofetil (formerly known as RS-61443) is a morpholinoethyl ester of mycophenolic acid. Mycophenolic acid is a unique immunosuppressive agent because of its mechanism of action. By inhibiting the de novo pathway of purine synthesis, mycophenolic acid suppresses lymphocyte function much more than that of neutrophil, erythrocyte, and other rapidly dividing cell lines which can use the salvage purine synthesis pathway. Mycophenolate mofetil has been shown to be an effective immunosuppressive agent in both animal models and early human trials. This article describes the history, biochemistry, pharmacology, in vitro and in vivo effects, and clinical trials of myophenolate mofetil. In addition, previously unpublished 3-year follow-up of heart transplant recipients receiving mycophenolate mofetil is reported.

Animals↗

PubMedDate not supplied

Immunosuppressive therapy, management, and outcome of heart transplant recipients during pregnancy.

To evaluate challenges facing heart transplant recipients who become pregnant, we surveyed 194 heart transplantation centers and reviewed the literature. Thirty-two known pregnancies in heart (n = 29) or heart-lung (n = 3) allograft recipients have resulted in 29 children, including two sets of twins. The method of delivery was most often vaginal (cesarean section rate was 33%), and premature delivery was common (41%). The onset of pregnancy from the time of transplantation was 2.6 +/- 0.3 years, with the age at conception ranging from 19 to 35 years. Hypertension (44%), premature labor (30%), and preeclampsia (22%) were the most frequent maternal complications. Four patients experienced a worsening of ongoing chronic renal insufficiency; four patients experienced infections during pregnancy, and six patients (22%) were successfully treated for rejection episodes during pregnancy by adjustments in standard immunosuppressive agents. No peripartum deaths were reported; three late deaths occurred. Of the 29 children born of heart transplant recipients who became pregnant, no fetal anomalies or neonatal deaths occurred. Prematurity (41%) and low birth weight (17%) were the most common complications. All children are reported in good health at 3.4 +/- 0.4 years of age. Most transplant recipients (59%) were being treated with triple-drug immunosuppression with azathioprine, corticosteroids, and cyclosporine during pregnancy. The most common alteration to immunosuppressive therapy during pregnancy (41%) involved increasing cyclosporine doses caused by decreasing cyclosporine levels during pregnancy. Twenty-two percent of patients underwent empiric lowering of cyclosporine doses during pregnancy; four patients continued with corticosteroid tapering during pregnancy, and four patients increased corticosteroid doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

Vascular rejection in heart transplantation: clinical correlation, treatment options, and future considerations.

Vascular rejection injures the vascular endothelium in cardiac allografts in the absence of significant intramyocardial lymphocytic infiltration. When compared with cellular rejection, vascular rejection occurs earlier after transplantation, is more resistant to immunosuppressive augmentation, causes more allograft dysfunction, and is associated with a higher frequency of allograft loss. Between January 1990 and October 1992, acute hemodynamically significant vascular rejection developed in 13 of 170 patients (8%). Endomyocardial biopsy specimens revealed the typical findings of endothelial cell activation, immune complex deposition, and interstitial fibrin deposition in the absence of significant lymphocytic infiltration. All patients had clinical evidence of allograft dysfunction. In addition to high-dose corticosteroids, all patients received cyclophosphamide as an oral pulse for 4 days and underwent plasmapheresis for 3 consecutive days. Eight patients received OKT3 (n = 6) or antilymphoblast globulin (n = 2), and nine patients underwent systemic anticoagulation. Six patients required inotropic therapy for hemodynamic instability. Although one patient died during the initial episode, rejection resolved and left ventricular function returned to normal in 12 of 13 patients. However, vascular rejection recurred in three patients, two of whom subsequently died. Two other patients died during late follow-up because of noncompliance. Eight patients remain alive with normal allograft function and angiographically normal coronary arteries. Whereas the addition of cyclophosphamide and plasmapheresis may improve the outcome of vascular rejection, the results of treatment with currently available treatment modalities remain unacceptably poor.

Adolescent↗

PubMedDate not supplied

Methotrexate for rejection prophylaxis after heart transplantation.

BACKGROUND: The addition of vincristine to "quadruple-drug" induction immunotherapy (OKT3, cyclosporine, azathioprine, prednisone) after heart transplantation decreases the incidence of rejection but is limited by neurotoxicity. We hypothesized that methotrexate, when added to quadruple therapy, may also decrease the incidence of rejection but with less toxicity. METHODS: We randomized 36 heart transplant recipients to receive either quadruple therapy (OKT3, cyclosporine, azathioprine, corticosteroids) (n = 19) or quadruple therapy plus methotrexate (n = 17). Methotrexate was given weekly for 8 weeks beginning at the conclusion of OKT3 therapy (postoperative days 8 to 16), and dosed according to white blood cell count. RESULTS: Six methotrexate patients did not complete the protocol, leaving 11 patients on weekly methotrexate at a mean dose of 8.6 mg/week (range 0 to 15 mg/wk). Multiple indexes of rejection were similar between the two groups, including days to first rejection, number of treated rejection episodes, mean biopsy scores, and number of patients requiring intravenous corticosteroids or antilymphocyte therapy. Toxicity and infection rates were not significantly different between the two groups. CONCLUSIONS: Although toxicity was minimal, an 8-week course of methotrexate appears to add no significant benefit to quadruple-drug immunotherapy.

Azathioprine↗