PURPOSE: To study the effects of different formulations of topical cyclosporine (Cyclosporin A [CsA]) on corneal allograft rejection in a rat model. METHODS: Female Lewis rats received penetrating keratoplasties from female Wistar-Furth donors. A total of 78 allogeneic grafts were performed. An additional 15 syngeneic grafts (Lewis) were used as technical controls. Two CsA preparations with equivalent drug concentrations (2.1 mg/ml) were applied as drops: CsA encapsulated in large unilamellar liposomes (CsA-LIP) and CsA dissolved in olive oil (CsA-DR). Allogeneic grafts were randomly assigned to receive CsA-LIP or CsA-DR beginning on the day of surgery five times daily for 10 days. Animals without any treatment or receiving empty liposomes (EM-LIP) were used as treatment controls. Grafts were graded three times weekly and a rejection index was generated based on graft clarity, neovascularization, and vessel size. RESULTS: All syngeneic grafts remained clear over the observation period of 60 days. Rejected allogeneic grafts without any treatment and those receiving EM-LIP or CsA-DR showed a mean survival time (+/- standard deviation) of 14 +/- 4, 14 +/- 5, and 14 +/- 4 days, respectively. There was no significant difference in mean survival time between the grafts without any treatment and those in CsA-DR or EM-LIP treatment groups. The mean survival time of rejected grafts in animals receiving CsA-LIP was prolonged to 20 +/- 4 days. There was a significant difference in the mean survival time between the CsA-LIP treatment group and groups receiving CsA-DR, EM-LIP, or no treatment (P < or = 0.05). The Kaplan-Meier survival curve of the CsA-LIP treatment group was significantly different from the other experimental groups. The graft survival rate in the CsA-LIP group was 77%, whereas the rate was 37% in the non-treated group, 45% in the CsA-DR group, and 36% in the EM-LIP group. CONCLUSION: Encapsulation of CsA in liposomes might be a promising formulation for use in the prevention of corneal graft rejection.

Animals↗

PubMed1993

Ocular absorption of topically applied FK506 from liposomal and oil formulations in the rabbit eye.

PURPOSE: To investigate the use of topically applied FK506, a new immunosuppressive compound, systemic and ocular absorption was determined in serum and various ocular tissues. METHODS: Two drops of 20 microliters FK506 were applied using oil dissolved (OD-FK506) or liposome-bound (LIP-FK506) drug. FK506 concentrations were measured at intervals of 30, 60, and 120 minutes by immunoassay. RESULTS: After application of OD-FK506, the highest concentrations of FK506 were found in the cornea and the conjunctiva (200-1200 ng/g) with substantial drug also present in anterior and posterior sclera. Relatively low concentrations were measured in the aqueous and vitreous humors (0.2-1.0 ng/g) of these animals. Using the same treatment regimen, LIP-FK506 was effective in delivering significantly higher drug concentrations (P < 0.05) to all ocular tissues and particularly aqueous humor (5-28 ng/g) and vitreous humor (12-22 ng/g) at all time points. During the observation period drug concentrations produced by LIP-FK506 remained well above the therapeutic range. FK506 levels were not detectable in serum (< 0.2 ng/ml) with either drug formulation. CONCLUSION: These findings indicate that liposomes may be a promising formulation for topical use of FK506 in ocular immune-mediated diseases.

Absorption↗

PubMed1993

Prospective evaluation of malignant neoplasms in cardiac transplant recipients uniformly treated with prophylactic antilymphocyte globulin.

Although there is convincing evidence that prophylactic administration of high doses of the monoclonal antibody OKT3 predisposes patients to an increased prevalence of early posttransplantation malignancy, particularly posttransplantation lymphoproliferative disease, it is indeterminate whether polyclonal antilymphocyte globulin poses a similar hazard. We reviewed the outcome of 112 consecutive cardiac transplant recipients who received uniform immunosuppression, including induction therapy with antilymphocyte globulin, and were prospectively followed-up for a median duration of 41.5 months (range 1 to 81 months). No patients had posttransplantation lymphoproliferative disease. Nine malignant neoplasms (8%) were detected from 6 to 70 months after transplantation. Four patients with cutaneous neoplasms were alive and well at the time this article was written. Three patients died of disseminated adenocarcinoma 6 months, 17 months, and 60 months after transplantation. One patient was undergoing treatment of Kaposi's sarcoma at the time this article was written, and another was undergoing treatment of transitional bladder cell carcinoma. Actuarial survival for all patients was 88% at 1 year and 79% at 5 years. Moderate doses of induction antilymphocyte globulin may facilitate rapid reduction of maintenance cyclosporine and steroid doses, thereby decreasing the duration of intense immunosuppression and lowering the risk of posttransplantation lymphoproliferative disease. Testing this hypothesis would require the development of reliable and reproducible in vivo assays to prospectively assess immune status.

Adolescent↗

PubMed1992

HCFA reverses requirement that hospitals treat patients transferred from Mexico.

Explore the source record for details and available documents.

Centers for Medicare and Medicaid Services, U.S.↗

PubMed1992

Hospitals gird to fight 'disease of the future'.

With cancer expected to strike one in three Americans now living, the disease is transforming the way hospitals are organized and the directions in which they will grow in the 1990s. Not only is cancer altering the way hospitals treat patients, but it's channeling patients into two arenas that hold the best chances for future growth--outpatient services and preventive medicine.

Ambulatory Care↗