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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. Source

Lemez P.,Hospital Jihlava | Kacirkova P.,Institute of Laboratory Diagnostics
International Journal of Laboratory Hematology | Year: 2014

Introduction: Nuclei of hairy cells (HC) are typically oval, round or indented, but atypical shapes are occasionally described in HCL and may lead to a provisional wrong diagnosis. Methods: The aim of this study was to quantify HC nuclei shapes classified into 11 categories on diagnostic bone marrow smears of 38 consecutive patients with HCL. Results: HC in all 33 patients with evaluable smears at diagnosis exhibited a round/oval nucleus in 60.8-95.8%, an indented nucleus in 3.4-24.5% and a kidney-shaped nucleus in 0.4-7.0%. Other shapes of HC nuclei were found only in a proportion of patients: nuclei with two indentations in 0.4-6.5% HC (28 patients), overlapped nuclei in 0.5-3.5% HC (17) and lobulated nuclei in 0.4-4.5% HC (15). Two per cent or less of HC had the following nuclear shapes: that of an opposite indentation and impression (14 patients), dumb-bell (13), ring (10), horseshoe (5), two nuclei (8 patients). Conclusion: Different shapes of HC nuclei similar to cells typical for other diagnoses are found usually in low frequencies. However, if their numbers are increased, they may cause diagnostic problems because cytology of blood and bone marrow smears is usually the first available diagnostic method. © 2014 John Wiley & Sons Ltd. Source

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. Source

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. Source

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. Source

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