Pharmacy study of natural health product adverse reactions (SONAR): a cross-sectional study using active surveillance in community pharmacies to detect adverse events associated with natural health products and assess causality.

Objectives: To investigate the rates and causality of adverse event(s) (AE) associated with natural health product (NHP) use, prescription drug use and concurrent NHP-drug use through active surveillance in community pharmacies.

Design: Cross-sectional study of screened patients.

Setting: 10 community pharmacies across Alberta and British Columbia, Canada from 14 January to 30 July 2011.

Two suspected cases of immunoglobulin-mediated interference causing falsely low vancomycin concentrations with the Beckman PETINIA method.

Objective: To describe 2 recent cases of suspected immunoglobulin-mediated interference with the Beckman Coulter particle-enhanced turbidimetric inhibition immunoassay (PETINIA) used to measure vancomycin serum or plasma concentrations and to review the existing literature.

Case Summary: A 64-year-old woman with a history of multiple immune-related comorbidities received vancomycin for treatment of a prosthetic joint infection growing coagulase-negative Staphylococcus spp. A 33-year-old man with a history of Felty syndrome received vancomycin for the treatment of methicillin-resistant Staphylococcus aureus pneumonia.

The effect of paraproteins and rheumatoid factor on four commercial immunoassays for vancomycin: implications for laboratorians and other health care professionals.

Background: Paraproteins, immunoglobulins (Igs), which are elevated in various autoimmune disorders, are known to interfere with various laboratory immunoassays, including vancomycin (VANC). Rheumatoid factor (RF), a known immunoassay interferant, may cause falsely elevated results.

Objectives: The aims of this study were to (1) evaluate the effect of 3 paraproteins (IgA, IgG, and IgM) on 4 commercial VANC immunoassays [fluorescence polarization immunoassay; enzyme multiplied immunoassay; 2 particle-enhanced turbidimetric inhibition immunoassays]; (2) determine the concentration at which the effect is obtained, and (3) examine the influence of RF on the VANC methods.

Determination of phenyltetrahydroimidazothiazole enantiomers (Levamisole/Dexamisole) in illicit cocaine seizures and in the urine of cocaine abusers via chiral capillary gas chromatography-flame-ionization detection: clinical and forensic perspectives.

Illicit cocaine laboratories in South America have been adding phenyltetrahydroimidazothiazole enantiomers (levamisole and/or tetramisole) to refined illicit cocaine for over 8 years. A chiral capillary gas chromatographic methodology is presented for phenyltetrahydroimidazothiazole enantiomer determination in illicit cocaine samples and in the urine of cocaine abusers. Illicit cocaine samples (N = 752) and urine specimens from cocaine abusers (N = 50) that contained phenyltetrahydroimidazothiazole were analyzed for enantiomeric composition.

Levamisole tainted cocaine causing severe neutropenia in Alberta and British Columbia.

Background: Five cases of severe neutropenia (neutrophil counts < 0.5 per 109 cells/L) associated with exposure to cocaine and levamisole, an antihelimithic agent no longer available in Canada, were identified in Alberta in 2008. Alberta and British Columbia (BC) public health officials issued an advisory and urged health care professionals to report cases to public health.

Evaluation of the accuracy of self-reported smoking in pregnancy when the biomarker level in an active smoker is uncertain.

Introduction: Our main objective was to estimate smoking prevalence as well as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of self-reported smoking among pregnant women in Edmonton, Canada, at 15-16 weeks of gestation.

Methods: We used serum samples to assemble a cohort of pregnant women who underwent an optional second-trimester screening for chromosomal and developmental anomalies. We determined cotinine concentrations for 92 self-reported smokers (11% of the cohort) and for 285 self-reported nonsmoking mothers, using adapted urinary cotinine assay.

Quantitative assessment of collagenase blends for human islet isolation.

Background: The variability in collagenase blends has been speculated as the single most important determinant of the success or failure in isolated islet yields in clinical islet transplantation. Examination of the formulation and potency of the widely used Liberase HI enzyme blend will uncover possible sources of imprecision.

Methods: High performance liquid chromatography (HPLC) and kinetic measurements of collagenase and protease activity were used to assess potency.

The EMIT 2000 tacrolimus assay: an application protocol for the Beckman Synchron LX20 PRO analyzer.

Objective: To develop and evaluate the performance of an application protocol for the EMIT 2000 tacrolimus (Tac) assay on the Beckman Synchron LX20 PRO Analyzer.

Design And Methods: Precision, accuracy, linearity, and lower limit of quantitation were investigated. Specimens from 212 kidney, liver, heart/heart-lung, and islet cell transplant patients were analyzed and results were compared to those from the Abbott MEIA II assay.

Isoflurane alters energy substrate metabolism to preserve mechanical function in isolated rat hearts following prolonged no-flow hypothermic storage.

Background: Isoflurane enhances mechanical function in hearts subject to normothermic global or regional ischemia. The authors examined the effectiveness of isoflurane in preserving mechanical function in hearts subjected to cardioplegic arrest and prolonged hypothermic no-flow storage. The role of isoflurane in altering myocardial glucose metabolism during storage and reperfusion during these conditions and the contribution of adenosine triphosphate-sensitive potassium (K(atp)) channel activation in mediating the functional and metabolic effects of isoflurane preconditioning was determined.

Some international approaches to aminoglycoside monitoring in the extended dosing interval era.

Aminoglycosides have rightly remained a cost-effective anti-microbial strategy for the treatment of gram-positive infections for some 25 years. However, in recent years there has been a review of the traditional thrice-daily administration regimen in favor of an extended dosing interval strategy that takes into account the individual patient's renal function. The general recommendations that have been provided to date have been adopted in various ways internationally.

Flumazenil in drug overdose: randomized, placebo-controlled study to assess cost effectiveness.

Objective: To investigate cost effectiveness of administration of flumazenil to patients presenting with suspected acute drug overdose.

Design: Double-blind, prospective, placebo-controlled randomized study.

Setting: University teaching hospital.

Rapamycin: distribution, pharmacokinetics and therapeutic range investigations: an update.

Based on the findings above, a number of conclusions can be made regarding the distribution, pharmacokinetics, and therapeutic range investigations with RAPA: (a) the majority of the drug is sequestered in erythrocytes, resulting in whole blood concentrations being considerably higher than plasma concentrations; (b) the drug is metabolized by the same cytochrome P450 3A enzyme involved in the metabolism of CsA and FK506. Metabolites are primarily simple demethylations and hydroxylations with 41-O-demethyl RAPA being the major metabolite both in vivo and in vitro; (c) the drug has a relatively long half-life in both humans and animals with 24-h trough concentrations being within the analytical range of HPLC when immunosuppressive doses are administered; (d) the drug exhibits a degree of proportionality between trough concentrations and dose; (e) a strong correlation exists between area under the concentration-time curve and trough blood concentration at steady state; (f) trough concentrations of the drug appear to be related to immunosuppressive efficacy and drug-related side effects; (g) the nephro- and neurotoxic properties of CsA are not augmented by concurrent treatment with RAPA; and (h) phase IIB trial results have shown a decrease of acute rejection episodes from 40% to < 10% among patients treated with full-dose CsA plus RAPA. The studies described here should provide a basis for the establishment of therapeutic monitoring protocols for RAPA.

Pharmacodynamic monitoring of mycophenolic acid in rabbit heterotopic heart transplant model.

Pharmacodynamic (PD) monitoring of immunosuppressive drugs provides a novel approach to optimization of drug therapy in transplant recipients. We chose to investigate this using mycophenolic acid (MPA), an immunosuppressive drug that mediates its effect by the inhibition of inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo biosynthesis of purines. A comparison of the relationship between PD versus drug level monitoring was performed using a heterotopic cardiac transplant in New Zealand white rabbits.

The EMIT Cyclosporine Assay: development of application protocols for the Boehringer Mannheim Hitachi 911 and 917 analyzers.

Objective: The purpose of this work was to develop applications for the EMIT Cyclosporine (CsA) Assay on the Hitachi 911 and 917 analyzers.

Methods And Results: Instrument settings were optimized to arrive at the following assay characteristics on the Hitachi 917. Limit of sensitivity was 50 micrograms/L.

Effect of assay methodology on pharmacokinetic differences between cyclosporine Neoral and Sandimmune formulations.

The new oral formulation of cyclosporine (CsA), Neoral (CsA-N), results in increased area under the curve (AUC) and decreased intra- and interindividual variation in blood concentrations and other pharmacokinetic (PK) parameters when compared with the current Sand-immune (CsA-S) formulation. The present study examines the effect of assay methodology on variability in blood concentrations and PK parameters for renal transplant patients receiving CsA-N and CsA-S and whether this variation is reduced with CsA-N. The results show that interindividual variations in PK parameters for patients receiving CsA-N were less than those for patients receiving CsA-S.

Pharmacodynamic assessment of mycophenolic acid-induced immunosuppression in renal transplant recipients.

The combination of pharmacokinetic and pharmacodynamic monitoring of immunosuppressive drugs provides a novel method for the optimization of drug dosing. We chose to investigate this with the use of mycophenolic acid (MPA), an immunosuppressive drug that mediates its effect by the inhibition of inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo biosynthesis of purines. The relationship between MPA concentration in plasma, IMPDH activity in whole blood, and nucleotide concentration in lymphocytes was investigated in renal-transplant recipients, who were randomized to receive either mycophenolate mofetil (MMF) (n = 5) or azathioprine (AZA) (n = 7), in combination with cyclosporine and prednisone.

Pharmacodynamic assessment of mycophenolic acid-induced immunosuppression by measurement of inosine monophosphate dehydrogenase activity in a canine model.

The combination of pharmacokinetic and pharmacodynamic (measurement of the biological effect) monitoring of immunosuppressive drugs provides a method for the optimization of drug dosing. We chose to investigate this using mycophenolic acid (MPA), an immunosuppressive drug that mediates its effect by the inhibition of inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo biosynthesis of purines. Using an assay developed for measurement of IMPDH activity in whole blood, the concentration required for 50% inhibition of IMPDH activity was approximately 200 mg/L (58 +/- 8.