Voriconazole pharmacokinetics in liver transplant recipients.

The objective of this study was to evaluate the pharmacokinetics of voriconazole and the potential correlations between pharmacokinetic parameters and patient variables in liver transplant patients on a fixed-dose prophylactic regimen. Multiple blood samples were collected within one dosing interval from 15 patients who were initiated on a prophylactic regimen of voriconazole at 200 mg enterally (tablets) twice daily starting immediately posttransplant. Voriconazole plasma concentrations were measured using high-pressure liquid chromatography (HPLC). Noncompartmental pharmacokinetic analysis was performed to estimate pharmacokinetic parameters. The mean apparent systemic clearance over bioavailability (CL/F), apparent steady-state volume of distribution over bioavailability (Vss/F), and half-life (t1/2) were 5.8+/-5.5 liters/h, 94.5+/-54.9 liters, and 15.7+/-7.0 h, respectively. There was a good correlation between the area under the concentration-time curve from 0 h to infinity (AUC0-infinity) and trough voriconazole plasma concentrations. t1/2, maximum drug concentration in plasma (Cmax), trough level, AUC0-infinity, area under the first moment of the concentration-time curve from 0 h to infinity (AUMC0-infinity), and mean residence time from 0 h to infinity (MRT0-infinity) were significantly correlated with postoperative time. t1/2, lambda, AUC0-infinity, and CL/F were significantly correlated with indices of liver function (aspartate transaminase [AST], total bilirubin, and international normalized ratio [INR]). The Cmax, last concentration in plasma at 12 h (Clast), AUMC0-infinity, and MRT0-infinity were significantly lower in the presence of deficient CYP2C19*2 alleles. Donor characteristics had no significant correlation with any of the pharmacokinetic parameters estimated. A fixed dosing regimen of voriconazole results in a highly variable exposure of voriconazole in liver transplant patients. Given that trough voriconazole concentration is a good measure of drug exposure (AUC), the voriconazole dose can be individualized based on trough concentration measurements in liver transplant patients.

Acute cellular rejection with CD20-positive lymphoid clusters in kidney transplant patients following lymphocyte depletion.

Lymphoid clusters (LC) containing CD20-positive B cells in kidney allografts undergoing acute cellular rejection (ACR) have been identified in small studies as a prognostic factor for glucocorticoid resistance and graft loss. Allograft biopsies obtained during the first episode of ACR in 120 recipients were evaluated for LC, immunostained with CD20 antibody, and correlated with conventional histopathologic criteria, response to treatment and outcome. LC were found in 71 (59%) of the 120 biopsies. All contained CD20 positive B cells that accounted for 5-90% of the LC leukocyte content. The incidence of LC was highest in the patients who had no lymphoid depletion or had been treated with Thymoglobulin preconditioning (79% vs. 75%, respectively) compared to 37% in patients pretreated with Campath (p = 0.0001). Banff 1a/1b ACR were more frequent in the LC-positive than the LC-negative group (96% vs. 80%, respectively; p = 0.0051). With a posttransplant follow-up of 953 +/- 430 days, no significant differences were detected between LC-postitive and LC-negative groups in time to ACR, steroid resistance, serum creatinine and graft loss. CD20+LC did not portend glucocorticoid resistance or worse short to medium term outcomes. CD20+LC may represent a heterogenous collection in which there may be a small still to be fully defined unfavorable subgroup.

Long-term outcomes of stereotactic breast biopsies.

Stereotactic core needle biopsies (SCNBs) are accurate and relatively convenient for the patient; however, the long-term follow-up of benign results has not been reported. All patients between 1993 and 1998 undergoing SCNB at a community-based hospital were entered into a registry. Follow-up was obtained by a retrospective analysis of the charts. Biopsies were performed on 865 lesions. One hundred thirty-one (15%) were malignant, 42 (5%) were suspicious for malignancy, 687 (79%) were benign, and five (1%) were lobular carcinoma in situ. Of the 42 patients with suspicious findings 38 underwent biopsy. Ten were malignant and 28 benign. Of the 687 patients with benign pathology, 377 had follow-up available with a mean length of 1.7 years. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of SCNB for benign lesions in our study are all 100 per cent. Eight lesions were worrisome and await final analysis. Of 687 patients with benign lesions 310 were lost to follow-up. This study suggests that patients with a benign diagnosis should be returned to routine mammography. These data also extend the reported follow-up to 1.7 years and establish an acceptable level of accuracy for SCNB. The lost patients remind us that follow-up is essential despite a benign diagnosis.