We report two cases of drug interaction between rifampicin and sirolimus in renal trans-plant patients who were diagnosed with tuberculosis after transplantation and induction of immuno-suppressive therapy with sirolimus. The dosage of sirolimus had to be increased, in one case up to six-fold and in the second case up to five-fold, to maintain serum levels after starting the rifampicin. The two patients tolerated the treatment well, with no signs of tuberculosis and good renal function.
Objectives: The surgical management and outcome of penetrating subclavian artery (SCA) injuries is presented in this article. Design: A retrospective chart review is used to detail the management and outcome of penetrating SCA injuries. Patients and methods: Patients with penetrating SCA injuries presenting to the Groote Schuur Hospital from January 1997 to December 2007 were reviewed. Demographic data, mechanism of injury, associated injuries, angiographic findings, surgical treatment, hospital stay, complications and mortality were noted. Results: Fifty patients with penetrating SCA injuries were identified from an operating trauma database. Stab and gunshot wounds accounted for 40 and 10 SCA injuries, respectively. The mean Revised Trauma Score (RTS) was 7.2. Angiography was obtained in 37 patients; false aneurysm (13) and total occlusion (nine) were the two most common findings. A median sternotomy was required in 25 (50%) patients and emergency room thoracotomy was performed in two patients (4%) for initial haemorrhage control. Primary repair of SCA injuries was possible in 52% of the patients. Three SCA injuries (6%) were ligated and one patient received an endovascular stent. Morbidity was restricted to associated brachial plexus injuries. The limb salvage rate was 100% and there were no deaths. Conclusion: Preoperative angiography was useful in planning an operative approach. Primary repair was possible in the majority of the patients and ligation of SCA injuries was life-saving in critically ill patients.
We investigated the dynamics of the CD4+ and CD8+ lymphocyte subsets, and the expression of activation markers in cardiac transplant recipients. We tested 132 peripheral blood samples from 62 cardiac transplant recipients using fluorescent staining and flow cytometry analysis. The results were correlated with histological rejection grade of concurrently taken biopsies, and 5-year survival of the recipients. A decrease in the total T lymphocyte subset, and in CD4+ lymphocytes was associated with higher rejection grade and lesser survival. An increase (5–11%) of double positive CD4+CD8+ lymphocytes was observed; these were mostly CD4brightCD8dim. The CD4/CD8 ratio was significantly (P<0.001) lower in the transplant recipients than in normal individuals. CD69 expression was higher than CD54 and CD154 expression on CD4 and CD8 lymphocytes of cardiac transplant recipients; correlation between these activation markers was excellent (P<0.001). Fluorescent staining for CD69 was often of low intensity. Multiple regression for % CD8+CD69+ cells and survival, and for % CD69+ T cells and rejection grade yielded a significant correlation (P<0.050). Both % CD8+CD69+ and % CD69+ T cells were significantly higher in samples with severe and moderate rejection grade (grades 3A, 3B and 4) than in samples which showed no, minimal or mild rejection (grades⩽2); P-values were 0.052 and 0.003, respectively. Preliminary results indicated that false negative results could be contributed to increased immunosuppression. We conclude that CD69 expression on circulating CD4 and CD8 lymphocytes is a useful parameter for the diagnosis of moderate and severe rejection.
We determined the human leucocyte antigen (HLA)-A, -B and -DR allele frequencies in recipients and donors of 115 cornea transplants, for recipients who developed graft rejection and those who did not. No difference in HLA allele frequencies of the recipients was found. The frequencies of the HLA-A26, -B35 and -B44 alleles in cornea donors were increased in recipients who developed graft failure. The detrimental effect on corneal graft survival of these alleles was significant (p < 0.001). No such effect was observed in renal transplantation. Corneal graft survival was similar when one or two A26, B35 or B44 alleles were present on the donor cornea. The negative effect was similar in magnitude to the previously reported negative effect of an HLA-B locus match between donor and recipient, When both a B-locus match and an A26, B35 or B44 allele were present, the negative effect on graft survival was twice as strong, indicating that different immune mechanisms are responsible for these phenomena.
We analyzed the influence on allograft survival of pretransplant panel reactive antibodies (PRA) <10%, PRA>10%, autoantibodies, cold antibodies and a positive B cell crossmatch in 807 renal and 237 cardiac transplant recipients. Donors and recipients were predominantly of mixed ancestry (Khoi, San, Xhosa and Caucasoid). Log rank analysis showed that PRA<10%, cold antibodies, and a positive B cell cross-match did not influence allograft survival. Autoantibodies were present only in renal recipients; they appeared to have a beneficial effect on allograft survival (P=0.06). PRA>10% appeared to have a detrimental effect on allograft survival in both renal (P=0.07) and cardiac (P=0.06) recipients. Since autoantibodies and PRA>10% had opposing effects, the results of renal recipients were reanalyzed after omission of the recipients with autoantibodies and coexisting PRA>10%. This resulted in augmentation of the protective effect for autoantibodies (P=0.027) and of the detrimental effect for PRA>10% (P=0.020). Two-year survival curves showed that when autoantibodies coexisted with PRA>10%, the long term, but not the short-term, detrimental effect of PRA>10% was attenuated. Patients with a positive B cell cross-match clustered in the PRA>10% group in both renal (PRA negative vs, PRA<10%: P=0.0251; PRA<10% vs. PRA>10%: P=0.0011) and cardiac (PRA negative vs, PRA>10%: P=0.0085) recipients. We conclude that PRA>10% is the best indicator to identify recipients at high risk for rejection, and that the influence of antibodies on graft survival can not reliably be established without taking coexisting antibodies into account.