Investigation of possible interference by digoxin-like immunoreactive substances on the Architect iDigoxin CMIA in serum samples from pregnant women, and patients with liver disease, renal insufficiency, critical illness, and kidney and liver transplant.

Background: Although the possible interference of digoxin-like immunoreactive substances (DLIS) on the Architect iDigoxin chemiluminiscent microparticle immunoassay (CMIA) has been emphasized by the manufacturer, a specific study about this subject has still not been carried out.

Methods: Apparent serum digoxin concentrations were determined using the Architect iDigoxin CMIA from Abbott Laboratories in digoxin-free pregnant women (n = 50), and patients with liver disease (n = 50), renal insufficiency (n = 50), kidney (n = 25) or liver (n = 25) transplant, and critical illness (n = 50).

Results: In all of the patients included in this study, apparent serum digoxin concentrations were lower than the correspondent quantification limit (< 0.

Impact of creatinine production on the agreement between glomerular filtration rate estimates using cystatin C-derived, and 4- and 6-variable Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations.

Background: It has recently been reported that patient selection has a strong impact on the agreement between glomerular filtration rate (GFR) estimates from serum cystatin C and creatinine. The aim of our study was to evaluate the effect of creatinine production rate (CPR) on this subject.

Material And Methods: GFR was estimated from serum cystatin C and from creatinine using the 4- and 6-variable Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in 50 healthy subjects, 43 patients with renal failure, 794 kidney and 104 liver transplant recipients, 61 patients with heart failure, 59 patients with biliary obstruction, and 113 critically ill patients.

Association between butyrylcholinesterase activity and low-grade systemic inflammation.

Background: Pro-inflammatory cytokine production is directly inhibited by acetylcholine (ACh), and a relationship between total circulating ACh hydrolytic capacity and inflammatory reactions has been previously reported. Butyrylcholinesterase (BChE) is the major ACh hydrolyzing enzyme in plasma, and the aim of our study was to evaluate its association with low-grade systemic inflammation.

Material And Methods: A total of 4,077 patients clinically managed in the Cardiology, Hypertension, and Digestive Medicine Units were included in our study.

Determination of everolimus in blood samples from kidney and liver transplant recipients using the sirolimus chemiluminescence magnetic microparticle immunoassay (CMIA) on the Architect-i1000® system.

Background: There is significant immunoassay cross-reactivity between everolimus and sirolimus, and their routine determination using a common method may reduce the reagent costs.

Methods: In 122 blood samples from kidney (n = 30) and liver (n = 92) transplant recipients, everolimus concentrations were determined using the Abbott IMx® microparticle enzyme immunoassay (MEIA) as previously described, and the Abbott sirolimus chemiluminescence magnetic microparticle immunoassay (CMIA) on the Architect-i1000® system.

Results: A high correlation coefficient (r = 0.

Apparent clearance of valproic acid in elderly epileptic patients: estimation of the confounding effect of albumin concentration.

Background: Valproic acid (VPA) apparent clearance (CL) estimated from total serum concentrations is analogous in elderly and non-elderly adult patients. As drug-protein binding decreases in old age, the aim of our study was to evaluate the confounding effect of the serum albumin concentration on the VPA apparent CL in elderly patients.

Methods: In 102 epileptic out-patients treated with VPA in monotherapy, serum total steady-state trough concentrations (Css) were determined.

Determination of blood everolimus concentrations in kidney and liver transplant recipients using the sirolimus antibody conjugated magnetic immunoassay (ACMIA).

Background: The aim of our study was to evaluate the possible determination of everolimus concentrations using the newly-introduced sirolimus antibody conjugated magnetic immunoassay (ACMIA).

Methods: Everolimus concentrations were determined in 100 blood samples from kidney (n = 47) and liver (n = 53) transplant recipients using the IMx sirolimus microparticle enzyme immunoassay (MEIA) from Abbott as previously described (Clin Biochem 2007;40:132-36) and sirolimus ACMIA from Siemens Healthcare Diagnostics Ltd.

Results: The ACMIA everolimus values were significantly higher than those of MEIA (p < 0.

Macromolecular complexes of cystatin C with circulating liver plasma membrane fragments and determination of serum cystatin C using the particle enhanced nephelometric immunoassay (PENIA) in kidney and liver transplantation and biliary obstruction.

Background: In a patient with biliary obstruction, a macromolecular complex of cystatin C with liver plasma membrane fragments, which also contain several membrane-bound enzymes, which may be removed by butanol extraction, has recently been characterised. This could lead to an underestimation of the glomerular filtration rate (GFR) from serum cystatin C concentration.

Methods: Using the particle enhanced nephelometric immunoassay (PENIA), serum cystatin C concentration was determined in 50 healthy controls, 43 patients with renal insufficiency, 68 kidney and 88 liver transplant recipients, and 60 patients with biliary obstruction.

A preliminary investigation on the possible association between diminished copper availability and non-alcoholic fatty liver disease in epileptic patients treated with valproic acid.

Background: Patients treated with valproic acid (VPA) present a high incidence of non-alcoholic fatty liver disease (NAFLD) (around 61%). Several recent studies suggest that low copper stores could be associated with NAFLD, and a significant decrease of copper availability in VPA-treated patients has been described.

Design And Methods: In 101 adult epileptic patients treated with valproic acid in monotherapy (n = 75) and polytherapy (n = 26) the copper availability was evaluated using the specific oxidase activity of ceruloplasmin (activity per unit mass of enzyme protein) and the copper/ceruloplasmin ratio.

A limited sampling strategy for estimation of the area under the curve (0 to 8 hours) of mycophenolic acid administered three times daily to liver transplant recipients.

Objectives: Gastrointestinal side-effects caused by mycophenolic acid (MPA) are frequent in liver transplant recipients, and in these cases a switch from two to three daily doses is usually recommended. However, a limited sampling strategy for the estimation of MPA area under the curve from 0 to 8 hours (AUC(0-8h)) has not been made.

Design And Methods: In 22 liver transplant patients who were administered MPA three times daily, the trapezoidal extrapolated MPA AUC(0-8h) values using a sampling time from 0 to 2 hours were calculated.

Interference of circulating endogenous antibodies on the Dimension® DGNA digoxin immunoassay: elimination with a heterophilic blocking reagent.

Only two cases have been previously described about circulating endogenous antibodies interference on the immunochemical determination of digoxin. In an elderly patient with history of social cat handling was observed a moderate positive interference (about 0.8 ng/mL) on the Dimension® DGNA digoxin immunoassay (capture rabbit antibody), which was eliminated treating the serum samples with a heterophilic blocking reagent.

Effect of valproic acid treatment on copper availability in adult epileptic patients.

Objectives: In rats a significant increase of the copper biliary excretion is produced by valproic acid administration, however, a conclusive study on the possible appearance of copper deficiency in humans during treatment with this drug has still not been carried out.

Design And Methods: In 101 adult epileptic patients treated in monotherapy (n=75) and polytherapy (n=26) with valproic acid, and 50 healthy controls, were determined serum copper, immunoreactive ceruloplasmin and its oxidase activity against o-dianisidine, in order to calculate the specific oxidase activity (activity per unit mass of enzyme protein) and copper/ceruloplasmin ratio.

Results: Specific oxidase activity of ceruloplasmin and copper/ceruloplasmin ratio were significantly lower in the groups of patients treated with valproic acid than in the controls.

Sirolimus and everolimus clearance in maintenance kidney and liver transplant recipients: diagnostic efficiency of the concentration/dose ratio for the prediction of trough steady-state concentrations.

Objectives: Therapeutic monitoring of sirolimus and everolimus is necessary in order to minimize adverse side-effects and to ensure effective immunosuppression. A sirolimus-dosing model using the concentration/dose ratio has been previously proposed for kidney transplant patients, and the aim of our study was the evaluation of this single model for the prediction of trough sirolimus and everolimus concentrations.

Methods: Trough steady-state sirolimus concentrations were determined in several blood samples from each of 7 kidney and 9 liver maintenance transplant recipients, and everolimus concentrations from 20 kidney, 17 liver, and 3 kidney/liver maintenance transplant recipients.

Glomerular filtration rate estimation using the Cockcroft-Gault and modification of diet in renal disease formulas for digoxin dose adjustment in patients with heart failure.

Objective: The aim of this study was to compare the estimated glomerular filtration rate (GFR) using the Cockcroft-Gault and the 4-, 5-, and 6-variable Modification of Diet in Renal Disease (MDRD) formulas for digoxin dose adjustment.

Methods: Steady-state serum digoxin concentrations were determined in 100 patients with heart failure and normal to severely impaired renal function. Total clearance (CL) and predicted average concentrations of digoxin were calculated using general pharmacokinetic principles.

Falsely increased blood tacrolimus concentrations using the ACMIA assay due to circulating endogenous antibodies in a liver transplant recipient: a tentative approach to obtaining reliable results.

The presence of endogenous antibodies in the serum of some patients has long been known to be a potential source of interference in immunoassays. We report falsely increased whole blood tacrolimus concentrations using the antibody conjugated magnetic immunoassay from Siemens HealthCare Diagnostics in a liver transplant recipient due to the presence of circulating endogenous antibodies (possibly heterophilic antibodies). Estimation of whole blood tacrolimus concentrations from the washed erythrocytes concentrations is proposed as a tentative approach for obtaining reliable results using the antibody conjugated magnetic immunoassay assay in these cases, leading to analogous blood tacrolimus concentrations to those produced by the microparticle enzyme immunoassay from Abbott Laboratories.

Determination of blood sirolimus concentrations in liver and kidney transplant recipients using the Innofluor fluorescence polarization immunoassay: comparison with the microparticle enzyme immunoassay and high-performance liquid chromatography-ultraviolet method.

Background: Although high-performance liquid chromatography (HPLC) is the method of choice for blood sirolimus determination, the microparticle enzyme immunoassay (MEIA) run on the IMx analyser is widely used in therapeutic monitoring of this immunosuppressant agent. The aim of our study was to evaluate the possible determination of sirolimus using the fluorescence polarization immunoassay (FPIA) commercialized for everolimus quantification.

Methods: Sirolimus concentrations were determined in whole-blood samples from liver and kidney transplant recipients using the Innofluor Certican FPIA (Seradyn Inc.

Comparison of blood tacrolimus concentrations in liver and kidney transplant recipients using ACMIA and MEIA immunoassays.

Background: Published data on the performance of the new Dade Behring antibody conjugated magnetic immunoassay (ACMIA) for tacrolimus determination are scarce. The aim of this study was to compare the results obtained using the ACMIA and Abbott microparticle enzyme immunoassay (MEIA), which is the most widely used method for therapeutic tacrolimus monitoring.

Methods: Trough tacrolimus concentrations were determined in 305 blood samples from kidney (n=138) and liver (n=167) transplant recipients using the ACMIA and MEIA immunoassays.

Relative proportions of serum carbamazepine and its pharmacologically active 10,11-epoxy derivative: effect of polytherapy and renal insufficiency.

Background: The proposed action mechanism and pharmacological activity of carbamazepine (CBZ) and its major metabolite, carbamazepine-10,11-epoxide (CBZE), are the same. The aim of our study was the investigation of the effect of concomitant antiepileptic treatment and renal insufficiency on the relative proportions of serum CBZ and CBZE.

Methods: Serum trough steady-state CBZ and CBZE concentrations were determined by high-performance liquid chromatography (HPLC) in 140 epileptic patients treated with CBZ in monotherapy (n=100) and polytherapy with phenytoin, phenobarbital and valproate (n=40).

LDL cholesterol estimation using the Anandaraja's and Friedewald's formulas in schizophrenic patients treated with antipsychotic drugs.

Objectives: The use of new antipsychotic drugs is associated with an increased risk of diabetes and metabolic syndrome, and the routine monitoring of blood lipids during treatment has been recommended. Recently, a new formula for the estimation of low-density lipoprotein (LDL) cholesterol from total cholesterol and triglycerides has been proposed by Anandaraja et al. (Int J Cardiol 2005; 102: 117), and the aim of our study was its evaluation in schizophrenic patients treated with antipsychotic drugs.

Evaluation of three dosing models for the prediction of steady-state trough clozapine concentrations.

Objective: Therapeutic drug monitoring of clozapine may be useful for the clinical management of schizophrenic patients treated with this atypical antipsychotic drug. The aim of our study was the evaluation of three models for the prediction of steady-state trough clozapine concentration.

Patients And Methods: The trough serum concentrations of clozapine and norclozapine were determined by high-performance liquid chromatography in 296 samples from a group of 21 schizophrenic patients selected for their good therapeutic compliance.

Effect of the hematocrit and its correction on the relationship between blood tacrolimus concentrations obtained using the microparticle enzyme immunoassay (MEIA) and enzyme multiplied immunoassay technique (EMIT).

The Abbott microparticle enzyme immunoassay (MEIA) and the Dade Behring enzyme multiplied immunoassay technique (EMIT) are the most frequently used methods in the therapeutic drug monitoring of tacrolimus; however, a hematocrit-dependent interference for the MEIA has been described. In 244 whole blood samples from patients with liver (n=152) and kidney (n=92) transplants, the MEIA/EMIT ratio presented a highly significant negative correlation with the hematocrit (r = -0.482, p < 0.

Clozapine and norclozapine concentrations in serum and plasma samples from schizophrenic patients.

At present, the determination of steady-state trough serum/plasma concentrations of clozapine is considered a useful tool for the clinical management of schizophrenic patients treated with this drug. In a previously published study, it was indicated that only plasma should be used to avoid a significant underestimation of clozapine and norclozapine concentrations; however, a formal evaluation of this topic has still not been made, and a consensus on the use of plasma or serum for therapeutic clozapine monitoring may be desirable. Paired samples of serum and plasma (K3EDTA solution contained in Vacutainer tubes) were obtained from 40 schizophrenic patients, and clozapine and norclozapine concentrations were determined by high-performance liquid chromatography.

Chitotriosidase activity in pleural effusions.

Chitotriosidase (ChT) is mainly secreted by monocyte-derived macrophages, and is considered a useful marker of macrophage activation. Macrophages represent the first line of defence against Mycobacterium tuberculosis, and consequently the study of ChT activity in pleural effusions (PE) would be of clinical value in the laboratory characterization of tuberculous pleurisy. ChT and adenosine deaminase (ADA) activities were determined in 12 tuberculous PE, 26 non-tuberculous lymphocytic PE and 25 neutrophilic PE.

Renal tubular dysfunction in schizophrenic patients treated with antipsychotic drugs.

Several factors have been considered in relation to the free radical formation in schizophrenia, such as the disease itself, drug treatment and smoking. Several chemicals and drugs may cause damage to the renal tubules by different subcellular mechanisms including oxidative stress, and the aim of our study was the investigation of tubular dysfunction in schizophrenic patients. The urinary excretion of beta-N-acetylhexosaminidase (Hex) and its isoenzymes Hex A and Hex B, alpha1-microglobulin, albumin, total proteins and fractionated porphyrins were determined in 45 schizophrenic patients treated with first- and second-generation antipsychotics.

Phenytoin immunoassay measurements in serum samples from patients with renal insufficiency: comparison with high-performance liquid chromatography.

The debate continues regarding the possible interference of phenytoin metabolites in phenytoin immunoassays, and its clinical importance for patients with renal failure. The aim of this study was to compare the results obtained using the Abbott fluorescence polarization immunoassay (FPIA), Dade enzyme-multiplied immunoassay technique (EMIT), and high-performance liquid chromatography (HPLC) to establish the significance of the differences in conditions of renal failure. Thirty-six adult patients who had been treated with phenytoin and whose renal function ranged from normal to severely impaired were chosen for this study.