Ustav Laboratorni Diagnostiky

Ostrava, Czech Republic

Ustav Laboratorni Diagnostiky

Ostrava, Czech Republic
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Kusnierova P.,UStav Laboratorni Diagnostiky | Zeman D.,UStav Laboratorni Diagnostiky | Sigutova R.,UStav Laboratorni Diagnostiky | Svagera Z.,UStav Laboratorni Diagnostiky | And 2 more authors.
Klinicka Biochemie a Metabolismus | Year: 2017

Objective: The study of abnormal gradients including new monoclonal immunoglobulins and oligoclonal bands in patients with multiple myeloma after autologous transplantation Design: Retrospective study. Material and Methods: 100 multiple myeloma patients after autologous transplantation between November 2013 and August 2016 from the Clinic of Haematooncology, University Hospital Ostrava, were included in the study. For the identification and quantification of paraproteins, standard serum protein electrophoresis and immunofixation electrophoresis were used. Exceptionally, in case of equivocal results, agarose isoelectric focusing with subsequent affinity-mediated immunoblotting was performed. Results: Changes in immunofixation result were observed 2 months (mean; range 1-8 months) after the autologous transplantation in 46 % of patients. In 6 (13%) of them isotype switch was observed, in 17 (37 %) transient oligoclonal profile, and in 23 (50 %) isotype shift as well as transient oligoclonal profile. Return towards the original immunofixation result was observed 14 months (mean; range 4-32 months) after the autologous transplantation. Conclusion: Observation of new monoclonal gradients or transient presence of oligoclonal bands in patients after autologous transplantation probably represents a transient phenomenon linked to the recovery of immunoglobulin production without any negative clinical significance in sense of a disease relapse.


Kacirova I.,Ustav klinicke farmakologie | Kacirova I.,Ustav laboratorni diagnostiky | Grundmann M.,Ustav klinicke farmakologie
Klinicka Farmakologie a Farmacie | Year: 2016

Therapeutic drug concentration monitoring was initiated for a number of antiepileptic drugs and currently is used to establish optimal therapy regimens for individual patients with epilepsy. The "newer" antiepileptic drugs generally have probably fewer adverse effects, more predictable pharmacokinetics, and wider therapeutic margins than "old" drugs. However, routine therapeutic drug monitoring is often used, particularly for lamotrigine, levetiracetam, stiripentol, and zonisamide, mainly due to inter-individual variation in metabolism and clearance. For other drugs, therapeutic drug monitoring may be clinically useful to assess compliance or to adjust dosing in organ failure. Generalized reference ranges have yet to be proposed for some newer antiepileptic drugs; however, even in the absence of generalized reference ranges, an individual therapeutic range can be established for patients treated with newer antiepileptic drugs. © 2016, SOLEN s.r.o. All rights reserved.


Halvova P.,Ustav laboratorni diagnostiky | Kacirova I.,Ustav laboratorni diagnostiky | Brozmanova H.,Ustav laboratorni diagnostiky | Grundmann M.,Ustav klinicke farmakologie Lekarske fakulty Ostravske univerzity
Klinicka Farmakologie a Farmacie | Year: 2015

Background: Cyclosporine A (CsA) is a potent immunosuppressive agent used after organ transplantation, including renal transplantation. CsA has also been shown to affect blood pressure (BP) diurnal variation by significantly increasing night-time blood pressure. Tight blood pressure control is a key objective in renal transplant patients, and for this purpose ABPM might be a useful tool. The aim of the study was to compare the relationship between blood and lymphocyte concentrations of CsA and its metabolites in patients with “dipping” or “non-dipping” status. Methods: Thirty-one stable renal transplant patients (16 men, 15 women) were included in this study. The mean patient age was 54 ± 12 years and the mean weight 75 ± 16 kg. Trough (C0) concentrations of CsA and its three metabolites, AM1, AM9, and AM4N, were estimated in blood and lymphocytes using the LC-MS/MS method. All patients underwent ABPM. The patients were divided into two groups: “dippers” (26 measurements) and “non-dippers” (with a nocturnal blood pressure fall < 10%, 25 measurements). GraphPad Prism version 5.00 for Windows was used for statistical analysis. A value of p < 0.05 was considered statistically significant. Results: The mean BP was 128 ± 11/75 ± 10 mm Hg and 124 ± 15/70 ± 11 mm Hg during daytime and during sleep, respectively. The mean cyclosporine trough level was 90.5 ± 40.1 μg/L (“dippers) and 97.3 ± 44.5 μg/L (“non-dippers”) in blood, and 11.4 ± 4.0 μg/L (“dippers”) and 11.8 ± 5.0 μg/L (“non-dippers”) in lymphocytes. Only one statistically significant difference (p = 0.0339) of AM4N concentrations in lymphocytes was found between “dippers” (0.4 ± 0.8 μg/L) and “non-dippers” (1.7 ± 2.6 μg/L). Conclusions: A 400% increase of lipophilic metabolite AM4N in lymphocytes in C0 can be the cause and/or predictor of “non-dipping” status in renal transplant patients. © 2015, SOLEN s.r.o.. All rights reserved.


Grundmann M.,Ustav klinicke farmakologie | Kacirova I.,Ustav klinicke farmakologie | Kacirova I.,Ustav laboratorni diagnostiky
Klinicka Farmakologie a Farmacie | Year: 2016

Therapeutic drug concentration monitoring has been used as a tool to optimize treatment of epilepsy for almost 60 years. The concept of the method rests on the assumption that clinical effects correlate better with drug concentrations than with the dose. It seeks to optimize the seizure suppressing effects of antiepileptic drugs while minimizing their adverse effects by managing their medication regimen with the assistance of information on the concentration of antiepileptic drugs in the serum, plasma or saliva. For most antiepileptic drugs, "reference ranges" have been reported which define the serum concentrations at which most patients are expected to exhibit an optimal clinical response. Due to individual variation, however, many patients may require concentrations outside the reference ranges. In many situations, patient management is best guided by determination of the "individual therapeutic concentration," defined as the concentration at which an individual has been found to achieve seizure freedom with good tolerability, or the best compromise between improvement in seizure control and concentration-related adverse effects. © 2016, SOLEN s.r.o. All rights reserved.


Koristkova B.,Ustav Klinicke Farmakologie | Koristkova B.,Ustav Laboratorni Diagnostiky | Grundmann M.,Ustav Klinicke Farmakologie
Klinicka Farmakologie a Farmacie | Year: 2016

Pharmacokinetic interactions between antiepileptic drugs are associated with enzymatic induction or inhibition. Felbamate, clobazam, lamotrigine, stiripentol, and sulthiame are significant inhibitors. Felbamate increases the levels of clonazepam, lamotrigine, mesuximide, valproic acid, and the active S(+)-enantiomer vigabatrin. Clobazam increases the levels of stiripentol, carbamazepine, and carbamazepine-10,11-epoxide. Stiripentol increases the levels of ethosuximide, phenobarbital, carbamazepine, clobazam and N-desmethylclobazam, primidone, and valproate. Acetazolamide, felbamate, phenytoin, mesuximide, oxcarbazepine, rufinamide, and sulthiame increase the levels of phenobarbital and phenytoin. The level of phenytoin is also increased by eslicarbazepine, clobazam, stiripentol, and topiramate. Phenobarbital and lamotrigine increase the AUC of retigabine. Valproic acid increases the levels of phenobarbital, lamotrigine, and rufinamide, while reducing the levels of felbamate and topiramate. It may decrease, increase as well as not affect the levels of ethosuximide, phenytoin, and carbamazepine. Eslicarbazepine, carbamazepine, phenytoin, phenobarbital, mesuximide, oxcarbazepine, primidone, and vigabatrin are enzymatic inductors. A reduction in levels due to induction may occur with eslicarbazepine, ethoxusimide, phenytoin, felbamate, pheno-barbital, clobazam, clonazepam, lacosamide, lamotrigine, levetiracetam, oxcarbazepine including its metabolite, perampanel, pregabalin, primidone, retigabine, rufinamide, stiripentol, sulthiame, tiagabine, topiramate, valproate, and zonisamide. Pregabalin increases the clearance of tiagabine and topiramate. Retigabine reduces the AUC of phenobarbital. Interactions involving absorption, distribution, or excretion are less frequent: acetazolamide reduces the absorption of primidone. Phenobarbital increases the free fraction of valproate, while valproate increases that of phenytoin and oxcarbazepine. Gabapentin decreases the excretion of felbamate. Adverse pharmacodynamic interactions involve side effects: concomitant treatment with agents acting at the sodium channel increases the risk of neurotoxicity. During the administration of lamotrigine with valproate, tremor can occur and the risk of skin rash and Stevens-Johnson syndrome increases. The incidence of encephalopathy after valproate increases when it is combined with topiramate, levetiracetam, and in triple combination with oxcarbazepine and lacosamide. Concomitant administration of carbonic anhydrase inhibitors increases the risk of nephrolithiasis. When sulthiame and primidone are combined, children can develop dizziness, unsteady gait, and drowsiness. Phenobarbital delays the onset of action of vigabatrin. © 2016, SOLEN s.r.o. All Rights Reserved.


Kelbich P.,R.Ø.S.A. | Kelbich P.,Krajska zdravotni a.s. | Kelbich P.,Charles University | Hejcl A.,Masarykova nemocnice v Usti nad Labem | And 7 more authors.
Klinicka Biochemie a Metabolismus | Year: 2013

Objective: 1. Evaluate the numbers of cells in the cerebrospinal fluid (CSF), glucose concentrations in the CSF, values of the glucose quotient (Q glu.), lactate concentrations in the CSF and values of the coefficient of energy balance (KEB) as indicators of intensity of the inflammatory process in the CSF in groups of patients without CNS impairment, with slight serous inflammation of non-infectious aetiology in the CNS, with serous inflammation of infectious aetiology in the CNS and of patients with purulent inflammation in the CNS with extracellular bacteria in pathogenesis. 2. Compare the information potential of the used parameters of the glucose energy metabolism in the CSF compartments in our group of the investigated patients, i.e. concentrations of glucose in the CSF, values of the Qglu., concentrations of lactate in the CSF and values of the KEB. Design: Retrospective study. Material and Methods: We examined 133 CSF specimens in patients without CNS impairment, 227 CSF specimens in patients with slight serous inflammation with intrathecal synthesis of immunoglobulins of non-infectious aetiology in the CNS, 208 CSF specimens in patients with serous inflammation of infectious aetiology in the CNS and 140 CSF specimens in patients with purulent inflammation in the CNS with extracellular bacteria in pathogenesis. The objects of our interest were numbers of cells in the CSF, concentrations of glucose in the CSF, values of the Qglu., concentrations of lactate in the CSF and values of the KEB. The D'Agostino Omnibus test, the Kruskal-Wallis test with follow-up post hoc analysis using the Dunn's method, the Spearman correlation coefficient and the multinomial logistic regression analysis were used for statistical analysis of the examined parameters. Results: We did not find any changes in the numbers of cells in the CSF and in energy ratios in the CSF compartment of patients without CNS impairment. We found raised numbers of cells in the CSF and slight alterations of the glucose quotients, lactate concentrations in the CSF and the values of the KEB only in some patients with slight serous inflammations of non-infectious aetiology in the CNS. We observed manifestations of conspicuously increased intensity of inflammation in the numbers of cells in the CSF, lactate concentrations in the CSF and the values of the KEB in patients with serous inflammations of infectious aetiology in the CNS. Very high intensity of purulent inflammation in the CNS of bacterial aetiology was well apparent in all the evaluated parameters. Concerning the relationship, either direct or indirect, between the number of cells in the CSF and the other parameters, we found the highest correlation between the number of cells in the CSF and the values of the KEB (ρ = -0.770), followed by the lactate concentrations in the CSF (ρ = 0.734), the Qglu. (ρ = -0.676) and the glucose concentrations in the CSF (ρ = -0.544). We verified the applicability of the parameters mentioned above for prediction of the intensity of inflammation in the CNS via multinomial logistic regression analysis. The number of cells and the KEB, with 71.9 % and 71.6 % respectively, has the highest prediction potential of the correctly classified patients. They were followed by the lactate concentration in the CSF with 64.7 %, the Qglu. with 58.8 % and the glucose concentration with 54.7 % of the correctly classified patients. Conclusion: Our study supports the applicability of the numbers of cells in the CSF, the glucose concentrations in the CSF, the values of the Qglu., the lactate concentrations in the CSF and the values of the KEB for diagnosing CSF impairment and for monitoring the intensity of inflammation in the CNS. Further, the results enabled determination of the information potential of the energy parameters. The values of the KEB were most suitable for evaluation of the intensity of inflammation in the CNS. Less suitable results were achieved in case of the lactate concentrations in the CSF. Even worse results were observed in case of the values of Qglu. and the least suitable results were observed in case of the glucose concentrations in the CSF. © Ceská lékarská spolecnost Jana Evangelisty Purkyne, Praha 2013.


Dolecek R.,Ustav Laboratorni Diagnostiky | Crkvenjas-Nemeckova Z.,Ustav Laboratorni Diagnostiky | Pleva L.,Ustav Laboratorni Diagnostiky | Tvrdik J.,Ustav Laboratorni Diagnostiky | Svagera Z.,Ustav Laboratorni Diagnostiky
Osteologicky Bulletin | Year: 2015

Osteoporosis following burns has been repeatedly reported. The main objectives were to monitor 28 various markers in a group of 73 burnt patients (12 females, 61 males) on 7 occasions throughout a year (Days 1, 7, 14, 28, 56, 183 and 365), and to determine which markers could contribute to the development of osteoporosis, with general catabolism in acute phase response (APR) that may be excessive. So far, there are no clear criteria for such excessiveness although it has been repeatedly shown to exist. For six to twelve months, bone resorption markers such as CTX, NTX, PHP, DPD and, partly, acid phosphatase were significantly increased. For several weeks, the levels of catabolic interleukin-6 were increased; IL-10 was slightly increased for only a week after burns were sustained. Males had a decrease in anabolism resulting from a significant decrease in testosterone, dihydrotestosterone and f-testosterone lasting for several weeks. Both males and females had a temporary significant decrease in DHEA-S. Following burns, the levels of ionized calcium (iCa) and total calcium (tCa) in blood are significantly lower, with the decreased lasting for longer in case of iCa. The concentrations of PTH were relatively normal, with exceptions noted. In those who died after sustaining burns, however, the concentrations were often very high. Following burns, the levels of "anabolism" markers gradually rise such as alkaline phosphatase (ALP), osteocalcin, IGF-1 and des-acyl ghrelin. Initially, burn patients typically have high levels of 17β-estradiol; Cortisol levels are close to the upper limit of the normal range, with some extremely high as well as low levels being present. Urinary free Cortisol was high for several weeks. The mean levels of calcidiol, or 25 (OH)D, were lower than normal, and low in many individuals. There was a significant difference in many markers following burns and polytrauma. After polytrauma, PTH was very high, blocking IL-10 was high, both iCa and tCa were less reduced, and 17β-estradiol was lower. There was a high increase in ALP in polytrauma. Apparently, APR is sometimes excessive which might even cause harm to the burnt patient. In treatment, anabolics should be considered; an attempt to reduce the excessive APR should be made (successful administration of the neuroplegic mixture M2 in the past should be therefore remembered); and vitamin D3 should be administered following burns.


Kacirova I.,Ustav klinicke farmakologie | Kacirova I.,Ustav laboratorni diagnostiky | Grundmann M.,Ustav klinicke farmakologie
Kardiologicka Revue | Year: 2015

A key strategy in optimizing aminoglycosides and vancomycin therapy is therapeutic drug monitoring. It is a specific method of clinical pharmacology used to monitor the therapy using measurement of drug serum concentrations followed by interpretation by a clinical pharmacologist/pharmacist and good cooperation with the clinician. Therapeutic drug monitoring helps clinicians to quickly optimize aminoglycosides and vancomycin dosing regimens to maximize the clinical effect, minimize the toxicity of the drugs, decrease mortality and morbidity and reduce costs. Aminoglycosides (amikacin and gentamicin) constitute one of the oldest classes of antimicrobials. Despite their relative toxicity, mainly nephrotoxicity and ototoxicity, aminoglycosides are valuable in current clinical practice. They are bactericidal agents used against aerobic gram-negative infections, and in combination with a cell wall active antimicrobial-based regimen (e. g. b-lactams), also against gram-positive cocci. Aminoglycosides have a concentration-dependent bactericidal effect and a long post-antibiotic effect. There is accumulating evidence to show that large, single, daily doses (or more correctly, extended interval dosing) of aminoglycosides are associated with lower nephroand ototoxicity and comparable, if not superior, clinical outcomes than the same total dose administered in small, multiple doses. A general therapeutic range of aminoglycosides does not exist. Every patient has his/her own optimal target concentration based on the microorganism susceptibility, co-administered antibacterials, immune status and co-administration of other nephro-or ototoxic drugs. Minimum serum vancomycin trough concentrations should always be maintained above 10 mg/L to avoid development of resistance, nevertheless, trough concentrations > 20 mg/L are not recommended because of the risk of nephrotoxicity. For serious gram-positive infections vancomycin trough concentrations of 15-20 mg/L are recommended. In non-complicated infections (urinary tract infections or mild-to-moderate skin and soft tissue infections) trough concentrations of 10-15 mg/L should be sufficient. For continuous infusions of vancomycin target steady-state concentration values of 15-25 mg/L is optimal. We demonstrate some case reports of therapeutic monitoring of aminoglycoside antibiotics and vancomycine from our routine practice. © 2015, Ambit Media a.s. All rights reserved.


Grundmann M.,Ustav klinicke farmakologie | Kacirova I.,Ustav klinicke farmakologie | Kacirova I.,Ustav laboratorni diagnostiky
Kardiologicka Revue | Year: 2015

Introduction: Digoxin is a positive inotropic drug frequently prescribed in the treatment of chronic congestive cardiac failure. Recent evidence suggests that a lower therapeutic range of 0.5-0.9 ng/mL is associated with reduced mortality. With complex pharmacokinetic profile and narrow therapeutic index, its use in managing patients with heart failure can present a challenge to clinicians. Aim: To show the advantages of therapeutic drug monitoring for dosing of digoxin. Method: Bayesian analysis was used to predict the long-term serum concentration time profiles of digoxin, using the MW-Pharm 3.30 software. The serum levels of digoxin were determined by MEIA. Results: Three case reports are presented showing a prediction of steady-state digoxin level three days after the start of administration, drug-drug interaction between digoxin and spironolactone/carvedilol and an example of long-term patient non-compliance. Conclusion: The- rapeutic drug monitoring is very useful for prediction of serum levels of digoxin alone and in combination with different interacting drugs. It helps to understand compliance-influencing factors and to improve interventional strategies to increase digoxin compliance. © 2015, Ambit Media a.s. All rights reserved.


Zeman D.,Katedra biomedicinskych oboru | Zeman D.,Ustav laboratorni diagnostiky | Kusnierova P.,Katedra biomedicinskych oboru | Kusnierova P.,Ustav laboratorni diagnostiky
Klinicka Biochemie a Metabolismus | Year: 2016

Objective: Improvement of the procedure used for cerebrospinal fluid (CSF) and serum oligoclonal IgM detection. Design: Methodical study Material and Methods: Isoelectric focusing (IEF) in agarose gel followed by affinity immunoblotting. After choosing the best variant from the protocols tested, 35 paired CSF and serum samples were examined. Results: Improvement of IgM separation has been achieved by using narrower pH gradient (4-8), prefocusing step and cathodic application of samples. Efforts to separate IgM in native CSF or serum samples have been unsuccessful. Satisfactory results have been obtained using sample pretreatment with dithiothreitol, optionally followed by acrylamide pretreatment. Intrathecal synthesis of oligoclonal IgM was demonstrated in 11 out of 35 patients. Samples of symptomatic controls (n=3) or patients with a proved diagnosis of non-inflammatory neurological disease (n=9) were all negative. Oligoclonal IgM result correlated significantly with intrathecal IgM synthesis estimated either by Reiber's (P=0.007) or Auer's formula (P=0.026). Conclusion: The method described in this article enables sensitive and reproducible detection of oligoclonal IgM bands separated by IEF. Further research should address the optimisation of sample pretreatment as well as experiments aimed at separation of IgM in untreated cerebrospinal fluid and serum samples.

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