Efficacy and safety of sirolimus and everolimus in heart transplant patients: a retrospective analysis.

BACKGROUND: Since its introduction as an immunosuppressant in the late 1990s, sirolimus (SRL) has been used to prevent rejections after heart transplantation (HTx) in the United States. An analogue, everolimus (ERL) has been mainly used in Europe. We performed a retrospective longitudinal single-center study to evaluate efficacy and side effects of SRL and ERL. PATIENTS AND METHODS: We analyzed 71 patients, 39 in the SRL and 32 in the ERL group. The following data were collected: Trough levels of SRL and ERL, biopsy-proven rejections, renal function, blood lipids, hematology, blood pressure, pulse rate, and side effects (via an anonymous questionnaire). Follow-up time was 6 months. No prisoners or organs from prisoners were used in the study. RESULTS: Introduction of SRL or ERL into therapy took place 44 or 42 months (average) after HTx. SRL and ERL were equally effective in preventing rejection (8/39 versus 6/32). Hemoglobin levels decreased slightly in the SRL group (nonsignificant). Leucocytes and thrombocyte levels decreased in both groups (P < .05 only in the ERL group). Creatinine levels remained unchanged. Cholesterol and triglyceride levels increased significantly in the SRL group. High-density lipoprotein levels increased significantly in the ERL group. Vital signs remained stable in both groups. Side effects (mainly edema, gastrointestinal symptoms and infections) were considerable and prompted discontinuation in 39% of all patients in both groups. Infections were more frequent in SRL (18/39 versus 12/32, nonsignificant). Calcineurin therapy could be reduced by 25% in SRL and 45% in ERL. CONCLUSION: The impact of SRL and ERL on laboratory values and rejection rates, as well as on clinical parameters, is similar with a slight advantage to ERL regarding lipids and rate of infections (not significant). Both SRL and ERL allow an important reduction of calcineurin-therapy; however, both drugs have considerable side effects, which often require discontinuation of therapy.

Antibodies against different epitopes of heat-shock protein 60 in children with type 1 diabetes mellitus.

The aim of this study was to investigate the amounts and epitope specificity of antibodies against heat shock protein 60 (hsp60) in the sera of type 1 diabetic and healthy children. Antibodies specific for peptide p277 of human hsp60 and of M. bovis as well as for human hsp60, M. bovis hsp65 proteins were measured by ELISA. Other autoantibodies (islet cell antibodies, glutamate decarboxylase antibodies and IA-2 antibodies) were also determined. A total number of 83 serum samples from children with type 1 diabetes mellitus and 81 samples of control children were investigated. Epitope scanning of the hsp60 for linear antibody epitopes was carried out using synthetic peptides attached to pins. The antibody levels specific for peptide p277 of human- and of M. bovis origin were significantly (human: P=0.0002, M. bovis: P=0.0044) higher in the diabetic children group than in the healthy children. We could not find significant difference in the antibody levels to whole, recombinant hsp proteins among the examined groups of children. Antibodies to two epitope regions on hsp60 (AA394-413 and AA435-454) were detected in high titres in sera of children with diabetes mellitus. The first region similar to the sequence found in glutamate decarboxylase, whereas the second one overlaps with p277 epitope to a large extent. Presence of antibodies to certain epitopes of hsp60 (AA394-413-glutamic acid decarboxylase-like epitope; AA435-454-p277-like epitope) in diabetic children may reflect their possible role in the autoimmune diabetogenic process of the early diabetes.