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R C Manfro

Publications and source records attributed to R C Manfro.

At least 37 records · Page 2Linked to original sources
PubMed1990

Effect of food on the pharmacokinetics of cyclosporine in healthy subjects following oral and intravenous administration.

The pharmacokinetics of cyclosporine were studied in healthy subjects following administration of cyclosporine both orally (10 mg kg-1) and intravenously (4 mg kg-1) without and with high fat meals. Both blood and plasma samples (separated at 37 degrees C) were analyzed for cyclosporine concentration. Blood and plasma clearances of cyclosporine were calculated to be 0.36 and 0.47 L hr-1 Kg-1, respectively, and volume of distribution at steady state was calculated to be 1.21 L Kg-1, when cyclosporine was administered without a high fat meal. Using plasma analysis, the oral bioavailability of cyclosporine was estimated to be 21 and 79%, when administered without and with a high fat meal, respectively. When cyclosporine was administered intravenously together with a high fat meal, both clearance and volume of distribution increased significantly. Blood and plasma clearances of cyclosporine were 0.44 and 0.70 L hr-1 Kg-1, respectively, when cyclosporine was administered along with a high fat meal. We conclude that food not only enhances the absorption of cyclosporine but also enhances its clearance and volume of distribution. The observed variability in clearance, bioavailability, and volume of distribution values for cyclosporine across various pharmacokinetic studies can be partially accounted by the type of food administered and the sampling matrix used for analysis.

Administration, Oral↗
PubMed1989

"Anti-idiotypic" antibodies to HLA in transiently sensitized DST patients.

To test the hypothesis whether "anti-idiotypic" antibodies (Ab2) were involved in the loss of sensitization following donor-specific blood transfusions (DST), we investigated nine potential kidney graft recipients who became transiently sensitized after DST. Inhibiting "anti-idiotypic" activity of post-DST sera was determined using a complement-dependent cytotoxicity inhibition assay. The follow-up after DST ranged from 9 to 66 months. The nine patients developed 12 different anti-HLA antibodies (Ab1). Inhibiting post-DST serum activity was found in relation to four of them, while enhancement of cell killing caused by post-DST sera was observed in relation to six anti-HLA antibodies. In two patients presenting with more than one anti-HLA antibody inhibition was found with only one of the antibodies, indicating that the blocking of Ab1 was specific for the respective antibody. Enhancement was associated with a significantly prolonged sensitization of the patients. On the average, 5.7 +/- 5.0 months were necessary before "anti-idiotypic" activity was developed after the loss of sensitization, whereas enhancement was found immediately thereafter. Testing by flow cytometry indicated that enhancing sera still contained subthreshold levels of Ab1. Our results indicate that DST can induce the development of "anti-idiotypic" antibodies following a short period of sensitization. This finding provides further evidence that anti-idiotypic antibodies might be relevant factors in the eventual disappearance of sensitization to HLA antigens.

Adult↗
PubMedDate not supplied

Evaluation of apoptosis in peripheral blood lymphocytes of renal transplant patients.

The aim of this study was to evaluate the occurrence of apoptosis and the expression of FasL and IL-2 genes in apoptotic peripheral blood mononuclear cells (PBMC) at different posttransplant periods. Three groups of patients were studied: group 1, kidney transplant recipients at least 1 year posttransplant (n = 17); group 2, kidney transplant recipients at least 5 years posttransplant (n = 15); and a control group composed of 7 healthy subjects. Apoptosis was detected by annexin flow cytometry and gene expression by reverse transcription polymerase chain reactions. The percentage of apoptotic cells was significantly higher in groups 1 (42 +/- 4%) and 2 (37 +/- 3%) than the controls (27 +/- 2%; P < .0001). Apoptotic cells in group 1 was significantly higher than in group 2 (P < .005). A significant difference in FasL expression was observed between groups 1 and 2 (P < .001) and the immunosuppressive regimen. These findings suggest that PBMC of kidney transplant recipients are more susceptible to activation-induced cell death and that the Fas-FasL pathway is involved in this process.

Apoptosis↗
PubMedDate not supplied

[Sequential monitoring of renal transplant with aspiration cytology].

OBJECTIVE: To evaluate the utility of kidney aspiration cytology in the sequential monitorization of acute rejection in renal transplant patients. PATIENTS AND METHODS: Thirty patients were submitted to 376 aspirations. The clinical diagnoses were independently established. RESULTS: The representativity of the samples reached 82.7%. The total corrected increment index and the number of immunoactivated cells were higher during acute rejection as compared to normal allograft function, acute tubular necrosis, and cyclosporine nephrotoxicity. The parameters to the diagnosis of acute rejection were sensitivity: 71.8%, specificity: 87.3%, positive predictive value: 50.9%, negative predictive value: 94.9% and accuracy 84.9%. The false positive results were mainly related to cytomegalovirus infection or to the administration of OKT3. In 10 out of 11 false negative results incipient immunoactivation was present alerting to the possibility of acute rejection. CONCLUSIONS: Kidney aspiration cytology is a useful tool for the sequential monitorization of acute rejection in renal transplant patients. The best results are reached when the results of aspiration cytology are analyzed with the clinical data.

Acute Disease↗