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Background Therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) is commonly performed on plasma or serum. The use of dried plasma spots (DPSs) could represent a useful tool to facilitate sample shipment to reference laboratories. In this article, the authors describe the application of a commercially available UHPLC-MS/MS method for the determination of 9 commonly prescribed AEDs (levetiracetam, lacosamide, topiramate, ethosuximide, lamotrigine, rufinamide, zonisamide, primidone, and oxcarbazepine and its active metabolite 10-OH-monohydroxycarbazepine) to DPS collected on dried sample spot devices (DSSDs). Method Fifty microliters of plasma were spotted on DSSD. After being air-dried at room temperature, they were extracted using an organic extraction solution containing the appropriate deuterated internal standards. The chromatographic separation was performed on a UHPLC reversed-phase C-18 column, and the analytes were quantified using a triple quadrupole mass spectrometer (LC-MS/MS). Results The assay was linear over the concentration ranges tested with a total runtime of 10.3 minutes. Recovery ranged from 93.7% to 106.8%. Intraday and interday precision for all quality control levels, including lower limit of quantification, ranged from 2.1% to 18.4% and 2.1% to 13.2%. Intraday and interday accuracy biases ranged from -11.7% to 14.3% and -9.2% to 8.0%. The absence of matrix effects was also tested and confirmed. Real samples derived from patients under therapy were also analyzed, and the comparison of results obtained from DSSD with those obtained from plasma showed that the 2 matrices were interchangeable. Stability tests performed on both quality controls, and real samples demonstrated that DSSDs can be easily stored and shipped at room temperature for 15 days. Conclusions The application of the LC-MS/MS method allowed the authors to obtain a very specific, sensitive, and rapid (total runtime = 10.3 minutes) quantification of 9 AEDs starting from very low volumes of plasma samples. The main advantage of DPS over wet samples is room temperature storage and shipment, which lowers shipment costs and makes it suitable for routine TDM. Moreover, in comparison with other alternative matrices, DPS allows for the use of the same therapeutic ranges on which routine TDM is based. DPS on DSSD can thus be considered as a useful and cheap tool for the broader application of TDM.

Shiro, Marta; Charaudeau, PatriCk; Granato, LuiSa (eds.). 2012. Los generos discursivos desde multiples perspectivas: teorias y analisis. Madrid: Iberoamericana-Vervuert. 283 pp. ISBN 978-84-8489-680-7 (Iberoamericana) ISBN 978-3-86527-743-5 (Vervuert)

BACKGROUND Functional variants of inosine triphosphatase (ITPA) were recently found to protect against ribavirin (RBV)-induced hemolytic anemia. However, no definitive data are yet available on the role of plasma RBV concentrations on hemoglobin (Hb) decrement. Moreover, no data have been published on the possible interplay between these 2 factors. METHODS A retrospective analysis included 167 patients. The ITPA variants rs7270101 and rs1127354 were genotyped and tested using the χ test for association with Hb reduction at week 4. We also investigated, using multivariate logistic regression, the impact of RBV plasma exposure on Hb concentrations. RESULTS Both single nucleotide polymorphisms were associated with Hb decrease. The carrier of at least 1 variant allele in the functional ITPA single nucleotide polymorphisms was associated with a lower decrement of Hb (-1.1 g/dL), as compared with patients without a variant allele (-2.75 g/dL; P = 4.09 × 10). RBV concentrations were not influenced by ITPA genotypes. A cut-off of 2.3 μg/mL of RBV was found to be associated with anemia (area-under-receiver operating characteristic = 0.630, sensitivity = 50.0%, and specificity = 69.5%, P = 0.008). In multivariate logistic regression analyses, the carrier of a variant allele (P = 0.005) and plasma RBV concentrations

BACKGROUND Imatinib (Gleevec, STI-571), a 2-phenylaminopyrimidine-type competitive inhibitor of Bcr-Abl kinase, is the current frontline therapy for patients with chronic myeloid leukemia, and it induces durable responses and prolonging event-free and progression-free survival. Monitoring imatinib trough plasma concentration is a simple and rapid way to determine if the drug exposure exceeds the clinical efficacy threshold (1 mcg/mL). Because the target enzyme is located within cells, adequate drug intracellular concentrations are needed to inhibit its function. METHODS Chromatographic methods were used to quantify imatinib concentrations in both plasma and peripheral blood mononuclear cells collected from adult patients with chronic myeloid leukemia at the Department of Hematology. Samples were collected at steady state, and trough concentrations (24 ± 2 hours after last drug intake) were evaluated. Associations between variables were tested using the Pearson test; results are presented as mean (±SD). RESULTS Thirty-five samples from 24 patients were collected; patients were mainly men (16, 66.7%), aged 60 years old (±13.1) and with a body mass index of 24.8 (±4.4). A positive and significant correlation (r = 0.203; P = 0.027) was found between imatinib plasma and intracellular concentrations. CONCLUSIONS The observed correlation between plasma and intracellular imatinib concentrations suggests that they may be used to monitor drug exposure and treatment efficacy.

Intraductal papillary mucinous neoplasms (IPMNs) are rare pancreatic tumors, accounting for less than 1-2% of all neoplasms of the pancreas. The main characteristic of IPMNs is their favorable prognosis, as these pre-malignant or malignant lesions are usually slow-growing tumors and radical surgery is frequently possible. According to the localization of the lesions, three different tumor types have been identified: the main-duct IPMN, the branch-duct IPMN and the mixed-type IPMN (involving both the main pancreatic duct and the side branches). IMPNs do not present pathognomonic signs or symptoms. The obstruction of the main pancreatic duct system may cause abdominal pain and acute pancreatitis (single or recurrent episodes). The tumor may be incidentally discovered in asymptomatic patients, particularly in those with branch-duct IPMNs. In clinical practice, any non-inflammatory cystic lesion of the pancreas should be considered as possible IPMN. Computed tomography, magnetic resonance imaging with cholangiopancreatography and endoscopic ultrasonography can localize an IPMN and assess its morphology and size. The choice between non-operative and surgical management depends on the risk of malignancy and on the definitive distinction between benign and malignant IPMNs. Main-duct IPMNs have a high risk of malignant degeneration, especially in older patients. The clinical and radiological features, as well as treatment and outcome, of eight patients with IPMN (five with main-duct, two with branch-duct and one with mixed-type) observed by the authors over the last ten years are presented.

ObjectivesSymptomatic remission is increasingly perceived as a realistic objective of pharmacological treatment in patients with schizophrenia (2). However the relationships between symptomatic remission, as defined by standardized criteria, and functional outcome remain controversial. In the present study, we designed a one-year follow-up of clinically stable patients with schizophrenia and examined the relationships of clinical remission with several indices of psychosocial functioning.MethodsThirty-six patients with schizophrenia were included. All the evaluations were carried out both at baseline (T0) and after a one-year follow-up (T12). The categorization in psychosocial remission/non-remission was done by means of the Psychosocial Remission in Schizophrenia (PSRS) scale.ResultsBoth at T0 and at T12, R showed, with respect to NR, a better social functioning and a better quality of life. Correlation analysis revealed that the better the psychosocial functioning, the lower the scores on all psychopathological dimensions, except “anxiety/depression” and “hostility” at T0 as well as “anxiety/depression” at T12. At T0, 65% of R resulted also in psychosocial remission; at T12, this percentage reached 90%.ConclusionsOur findings suggest that symptomatic remission in schizophrenia is associated to functional outcome in the majority of cases, especially when both symptomatic and chronological criteria are met.