Variability of voriconazole plasma levels measured by new high-performance liquid chromatography and bioassay methods.

Voriconazole (VRC) is a broad-spectrum antifungal triazole with nonlinear pharmacokinetics. The utility of measurement of voriconazole blood levels for optimizing therapy is a matter of debate. Available high-performance liquid chromatography (HPLC) and bioassay methods are technically complex, time-consuming, or have a narrow analytical range. Objectives of the present study were to develop new, simple analytical methods and to assess variability of voriconazole blood levels in patients with invasive mycoses. Acetonitrile precipitation, reverse-phase separation, and UV detection were used for HPLC. A voriconazole-hypersusceptible Candida albicans mutant lacking multidrug efflux transporters (cdr1Delta/cdr1Delta, cdr2Delta/cdr2Delta, flu1Delta/flu1Delta, and mdr1Delta/mdr1Delta) and calcineurin subunit A (cnaDelta/cnaDelta) was used for bioassay. Mean intra-/interrun accuracies over the VRC concentration range from 0.25 to 16 mg/liter were 93.7% +/- 5.0%/96.5% +/- 2.4% (HPLC) and 94.9% +/- 6.1%/94.7% +/- 3.3% (bioassay). Mean intra-/interrun coefficients of variation were 5.2% +/- 1.5%/5.4% +/- 0.9% and 6.5% +/- 2.5%/4.0% +/- 1.6% for HPLC and bioassay, respectively. The coefficient of concordance between HPLC and bioassay was 0.96. Sequential measurements in 10 patients with invasive mycoses showed important inter- and intraindividual variations of estimated voriconazole area under the concentration-time curve (AUC): median, 43.9 mg x h/liter (range, 12.9 to 71.1) on the first and 27.4 mg x h/liter (range, 2.9 to 93.1) on the last day of therapy. During therapy, AUC decreased in five patients, increased in three, and remained unchanged in two. A toxic encephalopathy probably related to the increase of the VRC AUC (from 71.1 to 93.1 mg x h/liter) was observed. The VRC AUC decreased (from 12.9 to 2.9 mg x h/liter) in a patient with persistent signs of invasive aspergillosis. These preliminary observations suggest that voriconazole over- or underexposure resulting from variability of blood levels might have clinical implications. Simple HPLC and bioassay methods offer new tools for monitoring voriconazole therapy.

Department of Human Rights Division of Persons with Disabilities Annual Performance Plan Report, September 2005

This report is published in accordance with the Accountable Government Act to improve decision-making and increase accountability to stakeholders and citizens. This report contains performance information regarding our primary programs including, the Youth Leadership Forum, the College Leadership Forum, the State Access Grant and the Client Assistance Program. Major accomplishments this year include continuation of our core programs, a key role in the Iowa Great Places initiative and providing Cultural Competency training to governmental and non-governmental agencies.

Iowa Department of Corrections Annual Performance Report, 2004

Iowa Department of Corrections Annual Performance Report FY 2004

Deferred effects of nursery school on adolescents' school performance in Spain

This research analysis the long-term effects of nursery school attendance before the age of three in Spain. The effects are measured when the individuals are adolescents and attend secondary school. The article deals with the controversy over the long-term effects of nursery school attendance and its potential effect on reducing inequalities and social exclusion. The results estimate a significant long-term effect of nursery school attendance on improving educational performance, although the beneficial effects are lower among adolescents residing in the lower status households.

Iowa Veterans Home Agency Performance Plan, 2005

Annual Report, Agency Performance Plan

Iowa Veterans Home Agency Performance Plan 2004

Annual Report, Agency Performance Plan

Diagnostic performance of urinary metanephrines for the postmortem diagnosis of hypothermia.

The purpose of this study was to assess the diagnostic potential of urinary metanephrines and 3-methoxytyramine compared to urinary catecholamine determination in diagnosing antemortem cold exposure and fatal hypothermia. 83 cases of fatal hypothermia and 144 control cases were included in this study. Catecholamines (adrenaline, noradrenaline and dopamine), metanephrines (metanephrine, normetanephrine) and 3-methoxytyramine were measured in urine collected during autopsy. All tested analytes were significantly higher in hypothermia cases compared to control subjects and displayed a generally satisfying discriminative value, thus indicating urinary catecholamines and their metabolites as reliable markers of cold-related stress and hypothermia related-deaths. Metanephrine and adrenaline had the best discriminative value between hypothermia and control cases compared to other tested analytes, though with different sensitivity and specificity. These can therefore be considered the most suitable markers of cold-related stress.

Iowa Department of Education Performance Report, FY 2005

Agency Performance Report

Iowa Department of Administrative Services Agency Performance Plan, FY 2004

Agency Performance Plan

Iowa Department for the Blind Performance Plan, FY 2004

Agency Performance Plan

Iowa Department for the Blind Performance Plan, FY 2005

Agency Performance Plan

Iowa College Student Aid Commission Performance Report, FY 2004

Agency Performance Report

Department of Commerce Iowa Division of Banking Performance Report, FY 2004

Agency Performance Report from the Banking Division