Olga Cerna

Deep brain stimulation in acute management of status dystonicus

eep brain stimulation in acute management of status Deep brain stimulation in acute management of status dystonicus.

Enantiomeric determination of tramadol and O-desmethyltramadol in human plasma by fast liquid chromatographic technique coupled with mass spectrometric detection.

A rapid and sensitive method using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for enantiomeric determination of tramadol and its primary phase metabolite O-desmethyltramadol in human plasma has been developed. Tramadol hydrochloride-(13)C, d(3), was used as an isotopic labeled internal standard for quantification. The method involves a simple solid phase extraction. The analytes and internal standard were separated on Lux Cellulose-2 packed with cellulose tris(3-chloro-4-methylphenylcarbamate) using isocratic elution with hexane/isopropanol/diethylamine (90:10:0.1, v/v/v) at a flow rate of 1.3 mL/min. The APCI positive ionization mass spectrometry was used with multiple reaction monitoring of the transitions at m/z 264.2-->58.2 for tramadol, m/z 250.1-->58.2 for O-desmethyltramadol and m/z 268.2-->58.2 for internal standard. Linearity was achieved between 1-800 ng/mL and 1-400 ng/mL (R(2) > or = 0.999) for each enantiomer of tramadol and O-desmethyltramadol, respectively. Intra-day accuracies ranged among 98.2-102.8%, 97.1-109.1% and 97.4-102.9% at the lower, intermediate, and high concentration for all analytes, respectively. Inter-day accuracies ranged among 95.5-104.1%, 99.2-104.7%, and 94.2-105.6% at the lower, intermediate, and high concentration for all analytes, respectively. This assay was successfully used to determine the concentration of enantiomers of tramadol and O-desmethyltramadol in a pharmacogenetic study.

Thrombosis in thrombocythemic Ph-myeloproliferations is associated with higher platelet count prior to the event: results of analyses of prothrombotic risk factors from a registry of patients treated with anagrelide

Controversies still exist regarding definition of the thrombotic risks in Ph‐ (BCR/ABL1‐) myeloproliferative disorders with thrombocythemia (MPD‐T). Platelet counts at diagnosis are currently not taken as a risk factor of thrombosis. In our cohort of 1179 patients with MPD‐T, prospectively registered for anagrelide treatment, we found that the median platelet count prior to the thrombotic event was significantly higher than at time points without any ensuing thrombosis (453 vs. 400 × 109/L, P < 0.001), albeit higher platelet counts at diagnosis tended to be connected with fewer thrombotic events (in contrast to WBC counts at diagnosis). The JAK2V617F mutation predicted both arterial and venous events, while age >65 yr, hypertension, diabetes mellitus, smoking, elevated triglyceride and homocysteine levels predicted arterial events only. For venous events, the specific thrombophilic risk factors (factor V ‘Leiden’ and others), antiphospholipid antibodies, and elevated factor VIII levels played a major role. During anagrelide treatment (± aspirin), we documented a decrease in both venous (6.7‐fold) and arterial events (1.8‐fold), while bleeding (mostly minor events) increased twofold compared to history. Our results suggest that keeping platelet counts at low levels may be a meaningful therapeutic measure to prevent thrombosis, although their counts at diagnosis lack any prognostic value.

Interferon-α Revisited: Individualized Treatment Management Eased the Selective Pressure of Tyrosine Kinase Inhibitors on BCR-ABL1 Mutations Resulting in a Molecular Response in High-Risk CML Patients.

Bone marrow transplantation or ponatinib treatment are currently recommended strategies for management of patients with chronic myeloid leukemia (CML) harboring the T315I mutation and compound or polyclonal mutations. However, in some individual cases, these treatment scenarios cannot be applied. We used an alternative treatment strategy with interferon-α (IFN-α) given solo, sequentially or together with TKI in a group of 6 cases of high risk CML patients, assuming that the TKI-independent mechanism of action may lead to mutant clone repression. IFN-α based individualized therapy decreases of T315I or compound mutations to undetectable levels as assessed by next-generation deep sequencing, which was associated with a molecular response in 4/6 patients. Based on the observed results from immune profiling, we assumed that the principal mechanism leading to the success of the treatment was the immune activation induced with dasatinib pre-treatment followed by restoration of immunological surveillance after application of IFN-α therapy. Moreover, we showed that sensitive measurement of mutated BCR-ABL1 transcript levels augments the safety of this individualized treatment strategy.

Recurrent chromosomal breakpoints in patients with myelodysplastic syndromes and complex karyotype versus fragile sites

The myelodysplastic syndromes (MDS) represent a heterogeeous group of clonal disorders characterized by a maturation efect in hematopoietic stem cells. Ineffective hematopoiesis leads o cytopenia, clonal instability and an increased risk of transformaion to acute myeloid leukemia (AML). Biologic and genetic tests, in ddition to cytogenetic and molecular cytogenetic analyses of bone arrow cells, are needed to confirm an MDS diagnosis to place he patient in the correct predictive risk group and to select the ost effective therapy. The MDS karyotype has been established s an independent prognostic factor for survival, for response to herapy and for estimating the probability of AML evolution [1]. lonal chromosomal aberrations are detected in the bone marow (BM) in ∼50% of newly diagnosed cases of MDS, and up to 0% of cases have complex chromosomal aberrations (CCA). CCA re defined as numerical or structural changes involving three or ore chromosomes and/or rearrangements with three or more hromosomal breaks that are strongly associated with a very poor rognosis. Recurrent chromosomal aberrations (del(5)(q), monoomy 7, del(20)(q) and trisomy 8) have been described in BM rom ∼50% of newly diagnosed MDS patients, frequently as a part f CCA. Recently, there have been several published reports of hromosomal breakpoints that are associated with cancer genesis nd progression that have confirmed the co-localization of these hromosomal breakpoints to known fragile sites (FS). Breakpoints ssociated with structural changes that are localized to the FS (comon or rare) may play a significant role in inactivation of tumor uppressor genes or activation of oncogenes. FS can be defined as eritable-specific loci on human chromosomes that exhibit nonandom gaps or breaks when chromosomes are exposed to specific ell culture conditions. Rare fragile sites (RFS) are identifiable in less han 5% of the population, while common fragile sites (CFS) are ntrinsic parts of normal chromosome structure that are present n all individuals. We applied microarray technology to analyze enomic structural aberrations in MDS patients with complex aryotypes to identify recurrent chromosomal breakpoints and to valuate and compare their potential associations with FS.

737 POLYMORPHISM OF CYP2D6 IN THE CZECH POPULATION

Background and Aims: We compared a peridural analgesia with i.v. analgesia + paravertebral block T4-T8. Our aim was to evaluate analgesia with VAS, the appearance of collateral effects, the outcome and the leght of the stay in hospital. Methods: We performed continuous peridural analgesia (group A) and i.v. analgesia (group B) in two patient’s groups omogeneous for ASA class SAPS, age. In group A, we administered peridural Sufentanyl and Ketamine as preemptive analgesia. Intraoperatory and postoperatory (48/72 h) analgesia continued with peridural infusion of Ropivacaine and Sufentanil titrated on patient’s response to pain at rest or movement. In group B, preemptive, intra and postoperatory analgesia (48/72 h) was performed with ev elastomeric pump containing Sufentanyl, Catapresan, Plasil and Ranidil. Just before thoracotomy we made a paravertebral block T4-T8. General anaesthesia was performed in TIVA-TCI. Two groups were compared with t-Student test (p< 0.005). Results: Intraoperatory hypotension and bradycardia occurred in 20% of patients in group A, the mean VAS at rest was 1 and movement was 2 versus 4 and 6 in group B, (p< 0.05). The most common collateral effects, group A, were itching (7%), PONV (6%), respiratory failure (0.1%). No collateral effect showed up in group B. The mean stay in hospital was 5 day, group A versus 8, group B (p< 0.05). Conclusion: Group A showed up a significantly lower VAS, less days in hospital, no respiratory infections. However, continuous peridural in ASA III pt requires an accurate intraand post-operatory monitoring due to higher incidence of systemic collateral effects.