Banja Luka, Bosnia and Herzegovina
Banja Luka, Bosnia and Herzegovina

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Simundic A.-M.,University of Zagreb | Bilic-Zulle L.,Rijeka Clinical Hospital Center | Nikolac N.,University of Zagreb | Supak-Smolcic V.,Rijeka Clinical Hospital Center | And 9 more authors.
Clinical Chemistry and Laboratory Medicine | Year: 2011

Background: This cross-sectional multicentric survey study aimed to assess the quality of the extra-analytical phase of laboratory activities in some developing European countries and Mexico. We assessed the quality of the extra-analytical practices in participating laboratories regarding the: a) sample acceptance criteria; b) phlebotomy procedures; c) test results reporting and d) recording non-conformities. Methods: A survey was performed during the April-May 2009. A total of 15 clinical laboratories from the following countries were included: Bosnia, Croatia, Czech Republic, Hungary, Mexico, Poland, Portugal, Romania, Serbia and Ukraine. Questions were scored (scores from 1-4) and average scores was calculated for each category. Results: The overall score for all respondents (n=443) was 3.10±0.33. The average score was 3.11±0.56 for sample acceptance criteria, 2.76±0.58 for phlebotomy and 3.34±0.53, for test results reporting (F=116.49; p<0.001). Laboratory accreditation was associated with better practices and higher overall quality of the extra-analytical procedures (F=16.62; p<0.001). Moreover, the highest scores for sample acceptance criteria (F=8.32; p<0.001), phlebotomy procedures (F=13.28; p<0.001) and for reporting non-conformities (F=33.62; p<0.001) were observed for accredited laboratories or laboratories under preparation for accreditation. Conclusions: The overall quality of the extra-analytical practices in countries in this survey is not satisfactory. Phlebotomy practices are the most critical extra-analytical activity. Since laboratory accreditation was associated with better practices and higher overall quality of the extra-analytical procedures, we believe that the most significant improvement could be made by implementing the total quality management system and standardizing laboratory procedures. © 2011 by Walter de Gruyter.


Nagele P.,University of Washington | Meissner K.,University of Washington | Meissner K.,University of Greifswald | Francis A.,Medical University of Vienna | And 2 more authors.
Pharmacogenetics and Genomics | Year: 2011

Objectives: Folate metabolism is an important target for drug therapy. Drug-induced inhibition of folate metabolism often causes an elevation of plasma total homocysteine (tHcy). Plasma tHcy levels are influenced by several nongenetic (e.g. folate intake, age, smoking) as well as genetic factors. Over the last decade, several countries have implemented a nationwide folate fortification program of all grain products. This investigation sought to determine the impact of folate fortification on the relative contribution of environmental and genetic factors to the variability of plasma tHcy. Methods: Two cohorts were compared in this study, one from the United States (with folate fortification, n=281) and one from Austria (without folate fortification, n=139). Several environmental factors as well as previously identified gene variants important for tHcy levels (MTHFR C677T, MTHFR A1298C, MTRR A66G) were examined for their ability to predict plasma tHcy in a multiple linear regression model. Results: Nongenetic, environmental factors had a comparable influence on plasma tHcy between the two cohorts (R: approximately 0.19). However, after adjusting for other covariates, the tested gene variants had a substantially smaller impact among patients from the folate-fortified cohort (R=0.021) compared with the nonfolate-fortified cohort (R=0.095). The MTHFR C677T polymorphism was the single most important genetic factor. Male sex, smoking, and folate levels were important predictors for nonfolate-fortified patients; age was for folate-fortified patients. Conclusion: Population wide folate fortification had a significant effect on the variability of plasma tHcy and reduced the influence of genetic factors, most importantly the MTHFR 677TT genotype, and may be an important confounder for a personalized drug therapy. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Knoll T.,University of Tübingen | Schubert A.B.,Vivantes Klinikum Spandau | Fahlenkamp D.,Zeisigwald Clinics Bethanien | Leusmann D.B.,Malteser Hospital St Hildegardis | And 2 more authors.
Journal of Urology | Year: 2011

Purpose: The incidence and prevalence of urolithiasis are increasing but clinicians also have the impression that gender and age distributions of stone formers are changing. Moreover, regional differences in stone occurrence and composition have been observed. We analyzed such trends based on a large series of urinary stone analyses. Materials and Methods: A total of 224,085 urinary stone analyses from 22 German centers were evaluated to determine the incidence of stone composition and identify age and gender distributions from 1977 to 2006. A subset of 58,682 stone analyses from 1993 to 2006 was available to identify regional differences in stone composition in Germany. Results: Calcium containing calculi were most common in each gender. The overall male-to-female ratio of 2.4:1 increased from 1977 (1.86:1) to 2006 (2.7:1). The predominance of male calcium stone formers was even higher among elderly patients with a 3.13:1 ratio at ages 60 to 69. Since 1997, we observed a tendency toward an increasing incidence in middle-aged patients at ages 40 to 49 years. While the rate of infection stones constantly decreased, the incidence of uric acid calculi remained stable with an overall rate of 11.7% in males and 7.0% in females with a peak at higher ages. Cystine stones remained rare at 0.4% in males and 0.7% in females. In terms of regional analyses we noted great variation in stone composition in the 2 genders. Uric acid stones were more common in the eastern and southern regions but infection stones were mostly seen in eastern regions. Conclusions: In what is to our knowledge the largest series of stone analysis reported to date we identified an age and gender relationship of stone formation and composition. Regional variations are common and underline the influence of living habits, diet and standard of medical care on urinary stone formation. © 2011 American Urological Association Education and Research, Inc.


Fritsche-Polanz R.,Medical University of Vienna | Fritsche-Polanz R.,Institute of Laboratory Diagnostics | Fritz M.,Medical University of Vienna | Huber A.,Medical University of Vienna | And 6 more authors.
Molecular Oncology | Year: 2010

The KIT mutation D816V is associated with autonomous growth of mast cells (MC) and is detectable in most patients with systemic mastocytosis (SM), including cases with associated hematologic non-MC-lineage disease (AHNMD). Recently, KIT D816V was reported to be expressed in patients with acute myeloid leukemia (AML). However, it was not clarified whether these patients have co-existing occult SM. We investigated neoplastic cells in 101 patients with AML for expression of KIT D816V. In 7/101 patients (6.9%), KIT D816V was detectable. After a thorough histologic, molecular, and biochemical analysis, all 7 cases were found to have an associated SM, leading to the final diagnosis SM-AML. Microdissected tryptase+ MC displayed KIT D816V in all patients tested, whereas CD34+ blasts exhibited KIT D816V in only 2/4 patients. In one AML patient, SM without KIT D816V was detected. In all other patients, no associated SM was found, and leukemic blasts were negative for KIT D816V. In summary, our data show that KIT D816V in AML is highly associated with co-existing SM (SM-AML). Moreover, our data show that AML blasts may lack this transforming target-mutant, which may be important when considering the use of KIT D816V-targeting drugs for treatment of patients with KIT D816V-positive AML. © 2010 Federation of European Biochemical Societies.


Mitic G.,Institute of Laboratory Diagnostics | Kovac M.,National Blood Transfusion Institute | Jurisic D.,Institute of Laboratory Diagnostics | Djordjevic V.,University of Belgrade | And 4 more authors.
Gynecologic and Obstetric Investigation | Year: 2011

Background: Normal pregnancy is characterized by numerous changes in the hemostatic system, creating the hypercoagulable state which increases the risk of venous thromboembolic event (VTE) occurrence. The risk is further increased by the presence of inherited or acquired thrombophilia. Objective: In this study, we aimed to determine the prevalence of different types of thrombophilia in women with pregnancy-related VTE, and to investigate the possible connection between the type of thrombophilia and localization of VTE as well as the gestational age of VTE occurrence. Participants and Methods: Two hundred and two women with the first episode of pregnancy-related VTE and 130 controls were investigated. The antithrombin, protein C and protein S activity, APC resistance, FVG1691A, and FIIG20210A were determined. None of the investigated women was pregnant at the time of thrombophilia testing, and none was using oral contraceptives. Results: Thrombophilia was diagnosed in 95 patients (47%) and 7 controls (5.4%). The prevalence of FV Leiden, FIIG20210A mutations, antithrombin, PC and PS deficiencies taken together and combined thrombophilia was 22.3, 10.4, 6.9 and 6.9%, respectively. Significantly more frequent antepartum occurrence of VTE (11 vs. 3, p < 0.05) was found in women with natural coagulation inhibitor deficiency. Pulmonary embolism occurred more frequently in nonthrombophilic women (25 vs. 3, p < 0.001). Conclusion: Inherited thrombophilia was found to be considerably more frequently present in women with pregnancy- and puerperium-related VTE compared to healthy controls. Women with thrombophilia are at higher risk of developing thromboses localized in the iliacofemoral region, and women without thrombophilia are at higher risk of developing pulmonary embolism. Deficiency in natural coagulation inhibitors is associated with antepartum VTE occurrence. Copyright © 2011 S. Karger AG, Basel.


Strohmaier W.L.,Klinikum Coburg | Seilnacht J.,Klinikum Coburg | Schubert G.,Institute of Laboratory Diagnostics
Urologia Internationalis | Year: 2012

Background: Citrate is one of the most important inhibitors in urolithiasis. Hypocitraturia is a common risk factor in stone formers. Citrate excretion is regulated-amongst others-by acidosis and protein intake. A considerable number of stone formers, however, show hypocitraturia in the presence of normal urine pH levels. This is potentially due to defects in the renal tubular citrate carriers (NaDC 1 and 3) which may be genetically determined. Patients and Methods: 350 consecutive stone formers were examined. Exclusion criteria were urinary tract infection, hypokalemia, and steatorrhea. The following parameters were measured: serum: creatinine, calcium, potassium, and uric acid; urine: pH profiles, citrate, calcium, uric acid, ammonia, urea, and creatinine. Results: 83/350 patients were hypocitraturic (48 males, 35 females). 14/83 had low urine pH (≤6), 69/83 showed normal levels (>6). In the latter group there was a significantly higher recurrence rate (23 vs. 9%). The two groups were not different in serum parameters apart from uric acid. In urine, only pH and calcium (males) were significantly lower in the first group. Citrate did not correlate with urine pH and creatinine in the hypocitraturia-normal pH group, only with calcium in both sexes and urea and ammonia in females. In the hypocitraturia-low pH patients, there was no significant correlation between citrate and any other parameter tested. Conclusions: Hypocitraturia with normal urine pH is an entity indicating a high risk for recurrence. Since there was no correlation between citrate and pH, urea and ammonia, respectively, citrate excretion is not regulated in these patients as usual. There may be a link to calcium excretion. Potentially, these patients have defects in the renal tubular citrate carriers which may be genetically determined. Genetic examinations should be performed to elucidate a potential genetic disorder in hypocitraturia-normal pH stone formers. © 2012 S. Karger AG, Basel.


Raskovic A.,University of Novi Sad | Pavlovic N.,University of Novi Sad | Kvrgic M.,Pharmacy Novi Sad | Sudji J.,Institute of Occupational Health | And 3 more authors.
BMC Complementary and Alternative Medicine | Year: 2015

Background: Herbal supplements are widely used in the treatment of various liver disases, but some of them may also induce liver injuries. Regarding the infuence of thyme and its constituents on the liver, conflicting results have been reported in the literature. The objective of this study was to examine the influence of two commonly used pharmaceutical formulations containing thyme (Thymus vulgaris L.), tincture and syrup, on carbon tetrachloride-induced acute liver injury in rats. Methods: Chemical composition of investigated formulations of thyme was determined by gas chromatography and mass spectrometry. Activities of enzyme markers of hepatocellular damage in serum and antioxidant enzymes in the liver homogenates were measured using the kinetic spectrophotometric methods. Liver morphology was characterized by light microscopy using routine hematoxylin and eosin staining. Results: Thymol was found to be predominant active constituent in both tincture and syrup. Investigated thyme preparations exerted antioxidant effects in liver by preventing carbon tetrachloride-induced increase of lipid peroxidation. Furthermore, co-treatment with thyme preparations reversed the activities of oxidative stress-related enzymes xanthine oxidase, catalase, peroxidase, glutathione peroxidase and glutathione reductase, towards normal values in the liver. Hepatotoxicity induced by carbon tetrachloride was reflected by a marked elevation of AST and ALT activities, and histopathologic alterations. Co-administration of thyme tincture resulted in unexpected exacerbation of AST and ALT values in serum, while thyme syrup managed to reduce activites of aminotransferases, in comparison to carbon tetrachloride-treated animals. Conclusions: Despite demonstrated antioxidant activity, mediated through both direct free radical scavenging and activation of antioxidant defense mechanisms, thyme preparations could not ameliorate liver injury in rats. Molecular mechanisms of diverse effects of thyme preparations on chemical-induced hepatotoxicity should be more in-depth investigated. © 2015 Rašković et al.


Fiegel F.,TU Munich | Buhl A.,TU Munich | Jaekel H.-P.,Institute of Laboratory Diagnostics | Werle E.,Institute of Laboratory Diagnostics | And 3 more authors.
Lupus | Year: 2010

Patients with systemic lupus erythematosus (SLE) often develop a wide variety of serological manifestations including the presence of antibodies to double-stranded DNA (anti-dsDNA). Positivity for anti-dsDNA constitutes one of the laboratory criteria for the diagnosis of SLE and is therefore clinically relevant. We analyzed the diagnostic accuracies of four commercial anti-dsDNA immunoassays and compared the results with a recently established surface plasmon resonance (SPR) biosensor chip with covalently chip-immobilized dsDNA. The anti-dsDNA measurements were performed retrospectively in 50 patients with clinically proven SLE, 39 patients with other autoimmunopathies and 20 healthy controls. Data were evaluated by Receiver-Operator Characteristic (ROC) analysis, with special regard to SLE patients suffering from lupus nephritis. The ROC analyses for the four immunoassays and the SPR biosensor resulted in the following area-under-the-curve (AUC) and diagnostic efficiency (DE) values in descending order: Bindazyme AUC, 0.89; DE, 0.88; ELiA AUC, 0.89; DE, 0.86; SPR biosensor AUC, 0.82; DE, 0.80; Farrzyme AUC, 0.77; DE, 0.77; Farr AUC, 0.77; DE, 0.70. When considering the 22 nephritis SLE patients the following AUC were observed: Bindazyme 0.98; EliA 0.95; SPR biosensor 0.93; Farr 0.89; Farrzyme 0.88. Although various methodologies for the determination of anti-dsDNA were compared, the overall diagnostic accuracy was found satisfactory in all immunoassays. Best data were found for the Bindazyme assay. We referenced the measurements to our in-house SPR biosensor device which showed good AUC and DE values. When optimized, this technique, allowing to monitor antigen/ antibody interactions in real-time, may add a new analytical quality to the existing methods, potentially beneficial in diagnosis and clinical monitoring of SLE. © The Author(s), 2010.


Mitic G.,Institute of Laboratory Diagnostics
Medicinski pregled | Year: 2011

Recurrent foetal loss is a significant clinical problem, occurring in 1-5% of reproductive females. Inherited or acquired thrombophilia has been diagnosed in 50-65% of women with history of unexplained foetal loss. The low molecular weight heparin was applied in 24 women with inherited thrombophilia and previous recurrent foetal loss and in 6 women with primary antiphospholipid syndrome throughout their following pregnancies. The dose of low molecular weight heparin for the majority of women was 35-75 u/kg. Women with primary antiphospholipid syndrome received both low molecular weight heparin and aspirin 50-100 mg daily. Implementation of thromboprophylaxis resulted in successful pregnancy outcome in 29 out of38 pregnancies, which represents a significant improvement of pregnancy outcome in comparison to previous 81 pregnancy losses. The number of treated pregnancies in our study is small, but the rate of successful pregnancy outcomes is high (76%), indicating that low molecular weight heparin may be a promising approach to women with thrombophilia and recurrent foetal loss.


PubMed | Institute of Occupational Health, University of Novi Sad, Pharmacy Novi Sad and Institute of Laboratory Diagnostics
Type: | Journal: BMC complementary and alternative medicine | Year: 2015

Herbal supplements are widely used in the treatment of various liver disases, but some of them may also induce liver injuries. Regarding the infuence of thyme and its constituents on the liver, conflicting results have been reported in the literature. The objective of this study was to examine the influence of two commonly used pharmaceutical formulations containing thyme (Thymus vulgaris L.), tincture and syrup, on carbon tetrachloride-induced acute liver injury in rats.Chemical composition of investigated formulations of thyme was determined by gas chromatography and mass spectrometry. Activities of enzyme markers of hepatocellular damage in serum and antioxidant enzymes in the liver homogenates were measured using the kinetic spectrophotometric methods. Liver morphology was characterized by light microscopy using routine hematoxylin and eosin staining.Thymol was found to be predominant active constituent in both tincture and syrup. Investigated thyme preparations exerted antioxidant effects in liver by preventing carbon tetrachloride-induced increase of lipid peroxidation. Furthermore, co-treatment with thyme preparations reversed the activities of oxidative stress-related enzymes xanthine oxidase, catalase, peroxidase, glutathione peroxidase and glutathione reductase, towards normal values in the liver. Hepatotoxicity induced by carbon tetrachloride was reflected by a marked elevation of AST and ALT activities, and histopathologic alterations. Co-administration of thyme tincture resulted in unexpected exacerbation of AST and ALT values in serum, while thyme syrup managed to reduce activites of aminotransferases, in comparison to carbon tetrachloride-treated animals.Despite demonstrated antioxidant activity, mediated through both direct free radical scavenging and activation of antioxidant defense mechanisms, thyme preparations could not ameliorate liver injury in rats. Molecular mechanisms of diverse effects of thyme preparations on chemical-induced hepatotoxicity should be more in-depth investigated.

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