Cranioplasty Using Autoclaved Autologous Skull Bone Flaps Preserved at Ambient Temperature.

Context: Decompressive craniectomy followed by cranioplasty (CP) uses autologous craniectomy flaps or synthetic materials like titanium. Sterilization and preservation methods for the autologous bone flaps continue to be the surgeon's choice.

Aim: This study aimed to assess the short-term as well as long-term clinical outcomes of CP using autoclaved autologous bone grafts.

Clinical consequences of a miscalibrated digoxin immunoassay.

Background: A routine audit revealed that the analytical method used to measure digoxin concentrations by our statewide pathology provider in 2009 was underestimating digoxin concentrations by 10%. The assay was recalibrated by the manufacturer in 2010, but clinical outcomes of the underestimation were never measured. This is a pilot study to describe the prescribing behavior around out-of-range digoxin concentrations and to assess whether miscalibrated digoxin immunoassays contribute to clinically relevant effects, as measured by inappropriate alterations in digoxin doses.

Ropivacaine (total and unbound) and AGP concentrations after transversus abdominis plane block for analgesia after abdominal surgery.

Background: The goal of this study was to assess the safety of single bolus dose of ropivacaine (ROP) followed by continuous infusion through transversus abdominis plane block catheter. The aim was to determine ROP absorbed from the infusion site, changes in protein binding after surgery, and clinical determinants of adverse effects.

Methods: Twelve patients undergoing laparotomy, received bilateral transversus abdominis plane block under ultrasound guidance using a 20-mL bolus of 0.

A randomized double-blind clinical trial of a continuous 96-hour levobupivacaine infiltration after open or laparoscopic colorectal surgery for postoperative pain management--including clinically important changes in protein binding.

Background: Continuous local anesthetic infiltration has been used for pain management after open colorectal surgery. However, its application to patients undergoing laparoscopic colorectal surgery has not been examined. The aim of this prospective, randomized, double-blind, placebo-controlled clinical trial was to study the use of a commercial infiltration device in patients undergoing open or laparoscopic colorectal surgery, along with plasma concentrations of levobupivacaine, its acute-phase binding protein (alpha-1 acid glycoprotein, AAG), and the stress marker, cortisol.

Validation of an LC-MS/MS method to measure tacrolimus in rat kidney and liver tissue and its application to human kidney biopsies.

Background: Tacrolimus (TAC) has a narrow therapeutic index and high interindividual and intraindividual pharmacokinetic variability, necessitating therapeutic drug monitoring to individualize dosage. Recent evidence suggests that intragraft TAC concentrations may better predict transplant outcomes. This study aimed to develop a method for the quantification of TAC in small biopsy-sized samples of rat kidney and liver tissue, which could be applied to clinical biopsy samples from kidney transplant recipients.

Mass or molar? Recommendations for reporting concentrations of therapeutic drugs.

A working party (WP) from the Australasian Association of Clinical Biochemists, Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, Royal College of Pathologists of Australasia and Royal Australasian College of Physicians recommends the following: *mass units should be used for reporting therapeutic drug concentrations in Australia and New Zealand; and the litre (L) should be used as the denominator when expressing concentration. Examples of these units are mg/L and μg/L Exceptions to these principles include: *drugs for which there is current uniformity of reporting and supporting information using molar units, notably lithium (mmol/L) and methotrexate (μmol/L); *drugs that are also present as endogenous substances, where the units used routinely should continue to be used. This applies to many substances, including minerals (eg, iron; μmol/L), vitamins (eg, vitamin D; nmol/L) and hormones (eg, thyroxine; pmol/L).

Global health at home: a student-run community health initiative for refugees.

Free, student-run health initiatives for refugees fill a gap in needed health services and prepare medical students for understanding cross-cultural and systems-based medical practice.

Measurement of cyclosporine A in rat tissues and human kidney transplant biopsies--a method suitable for small (<1 mg) samples.

Therapeutic drug monitoring is used to individualize cyclosporine A (CsA) dosing after transplantation. However, immunosuppressant concentrations within the graft may better predict clinical outcomes, including toxicity. This study aimed to develop a method suitable for CsA measurement using routine fine-needle biopsy samples.

Effects of aging, renal dysfunction, left ventricular systolic impairment, and weight on steady state pharmacokinetics of perhexiline.

Materials And Methods: Two hundred patients at steady-state on long-term perhexiline were identified retrospectively. The ratio of maintenance dose to steady-state plasma concentration (dose:[Px]) was correlated with the following putative determinants via simple and multiple linear regression analyses: age, weight, left ventricular ejection fraction (LVEF), and creatinine clearance (CrCl, Cockroft-Gault formula). A Mann-Whitney U test was performed to determine if severe left ventricular systolic impairment affected maintenance dose.

Comparison of blood sirolimus, tacrolimus and everolimus concentrations measured by LC-MS/MS, HPLC-UV and immunoassay methods.

Objectives: An LC-MS/MS method was developed for simultaneous quantitation of tacrolimus, sirolimus and everolimus in whole blood, and compared to HPLC-UV and immunoassay methods.

Design And Methods: Blood (0.1mL) was analysed following solid-phase extraction and chromatographic resolution using a C18 column (45°C) and mobile phase of methanol/40mM ammonium acetate/glacial acetic acid (83/17/0.

Current status of therapeutic drug monitoring in Australia and New Zealand: a need for improved assay evaluation, best practice guidelines, and professional development.

The measurement of drug concentrations, for clinical purposes, occurs in many diagnostic laboratories throughout Australia and New Zealand. However, the provision of a comprehensive therapeutic drug monitoring (TDM) service requires the additional elements of pre- and postanalytical advice to ensure that concentrations reported are meaningful, interpretable, and clinically applicable to the individual patient. The aim of this project was to assess the status of TDM services in Australia and New Zealand.

Discordant results from "real-world" patient samples assayed for digoxin.

Background: Digoxin has a narrow therapeutic index and is primarily renally eliminated. To optimize dosing of digoxin, therapeutic drug monitoring has been important since assays became available in the 1970s. Immunoassays are not specific, and cross-reactivity with endogenous and exogenous compounds has been reported for more than 20 years.

Seradyn quantitative microsphere system lamotrigine immunoassay on a Hitachi 911 analyzer compared with HPLC-UV.

Lamotrigine (LTG) is used currently as monotherapy or, more frequently, as add-on therapy with other antiepileptic drugs. It demonstrates efficacy against partial seizures, primary and secondary tonic clonic seizures, absence seizures, and drop attacks. LTG pharmacokinetics is complicated by coadministration with other antiepileptic drugs such as valproic acid, phenytoin, or carbamazepine.

Measuring the unbound concentration fails to resolve analytic interferences in digoxin immunoassays.

Therapeutic drug monitoring of digoxin is well established in the clinical management of cardiac patients treated with the drug. Recently, target concentrations have been revised in patients with congestive heart failure to 0.5 to 0.

Cyclosporin therapeutic drug monitoring--an established service revisited.

Despite the routine application of therapeutic drug monitoring of cyclosporin (CsA) for two decades, there remain significant analytical issues. In addition, new developments have arisen in the delivery of this laboratory service as well as alternative clinical strategies for delivering optimal benefit to organ transplant recipients. Sample collection strategies are evolving away from the traditional pre-dose/trough (C0) sample in favour of estimates of the absorption phase in the first 4-6 hours after the oral dose of CsA.

Glucuronidation of mycophenolic acid by Wistar and Mrp2-deficient TR- rat liver microsomes.

In humans, mycophenolic acid (MPA) is metabolized primarily by glucuronidation in the liver to mycophenolate ether glucuronide (MPAGe) and mycophenolate acyl glucuronide (MPAGa). We have previously reported that in perfused livers of TR(-) rats (lacking the Mrp2 transporter), the clearance and hepatic extraction ratio of MPA were significantly lower compared with control Wistar rats, suggesting a difference in the capacity of the TR(-) rats to metabolize MPA in situ. There is very little information regarding the phase II metabolic capabilities of TR(-) rats; therefore, the aim of this study was to investigate the in vitro glucuronidation of MPA in Wistar and TR(-) rat liver microsomal protein.

Cloned enzyme donor immunoassay tacrolimus assay compared with high-performance liquid chromatography-tandem mass spectrometry and microparticle enzyme immunoassay in liver and renal transplant recipients.

The immunosuppressant drug tacrolimus has a narrow therapeutic index and is subject to a large variation in individual bioavailability and clearance. With its narrow therapeutic index, therapeutic drug monitoring is standard clinical practice in the management of transplant recipients. In this study, we report the evaluation of the cloned enzyme donor immunoassay (CEDIA) for the determination of whole-blood tacrolimus concentrations compared with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and microparticle enzyme immunoassay (MEIA) using samples obtained from liver (n = 100) and renal (n = 88) transplant recipients.

Effect of CYP2D6 metabolizer status on the disposition of the (+) and (-) enantiomers of perhexiline in patients with myocardial ischaemia.

Aims: This study investigated the effects of increasing doses of rac-perhexiline maleate and CYP2D6 phenotype and genotype on the pharmacokinetics of (+) and (-)-perhexiline.

Methods: In a prospective study, steady-state plasma concentrations of (+) and (-)-perhexiline were quantified in 10 CYP2D6 genotyped patients following dosing with 100 mg/day rac-perhexiline maleate, and following a subsequent dosage increase to 150 or 200 mg/day. In a retrospective study, steady-state plasma concentrations of (+) and (-)-perhexiline were obtained from 111 CYP2D6 phenotyped patients receiving rac-perhexiline maleate.

Safety of 96-hour incision-site continuous infusion of ropivacaine for postoperative analgesia after bowel cancer resection.

The aim of this study was to examine the safety of ropivacaine given to patients as a continuous infusion [0.2% (2 mg/mL), 5 mL/h for 96 hours] into a right lateral transverse incision using a portable elastomeric infusion pump after colon cancer resection. Blood samples were collected throughout the infusion and up to 12 hours after infusion and were analyzed by high-performance liquid chromatography (HPLC) for total and unbound ropivacaine concentrations in plasma.

CEDIA mycophenolic acid assay compared with HPLC-UV in specimens from transplant recipients.

Routine monitoring of mycophenolic acid (MPA) has been accepted as an essential tool in the management of this therapy in transplant recipients. The availability of simple, sensitive assays that measure MPA in plasma permits individualization of dosing regimens according to pharmacokinetic principles. We report the results of an evaluation of the CEDIA Mycophenolic Acid Immunoassay (Microgenics Corporation, Fremont, California) for the measurement of plasma MPA concentrations in a range of transplant indications and compare its performance and specificity to an established HPLC/UV method.

Therapeutic drug monitoring.

Purpose Of Review: Traditionally, therapeutic drug monitoring has been used for the management of epilepsy, cardiac arrhythmias, asthma and depression. This review provides an update, particularly for the newer clinical applications, and how therapeutic drug monitoring (including use of analytical and interpretation tools) can improve clinical outcomes.

Recent Findings: Improved drug assay methodologies and a greater understanding of pharmacokinetic and pharmacodynamic mechanisms has allowed the use of therapeutic drug monitoring for immunosuppressant drugs in organ transplant recipients, antiretroviral agents for HIV/AIDS and antimetabolite drugs for leukaemia.

A Bayesian approach for population pharmacokinetic modelling of sirolimus.

Aims: To explore a Bayesian approach for the pharmacokinetic analysis of sirolimus concentration data arising from therapeutic drug monitoring (poorly informative concentration-time point design), and to explore possible covariate relationships for sirolimus pharmacokinetics.

Methods: Sirolimus concentration-time data were available as part of routine clinical care from 25 kidney transplant recipients. Most samples were taken at or near the trough time point at steady state.