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Svalheim S.,University of Oslo | Mushtaq U.,University of Oslo | Mochol M.,Ostfold County Hospital | Luef G.,Innsbruck Medical University | And 3 more authors.
Acta Neurologica Scandinavica | Year: 2013

Objectives: The aim of the study was to investigate immunoglobulin levels in patients with epilepsy using the antiepileptic drugs (AED) levetiracetam (LEV), carbamazepine (CBZ), or lamotrigine (LTG). Methods: A total of 211 patients and 80 controls (age: 18-45 years) of both genders were included. The patients had been treated with either LEV (n = 47), CBZ (n = 90), or LTG (n = 74) monotherapy for at least 6 months. Total concentrations of immunoglobulin G (IgG), IgG subclasses (IgG1, IgG2, IgG3, and IgG4), immunoglobulin A (IgA), and immunoglobulin M (IgM) were measured. Smoking, drinking habits, and physical activity were recorded, and body mass index (BMI) was calculated. Results: A significantly lower total IgG and IgG1 was found in both men and women treated with LTG and in men on CBZ. IgG2 and IgG4 were also lower in LTG-treated women, and IgA and IgM were lower in LTG-treated men. Patients treated with LEV did not differ from the control group. Conclusions: Low levels of immunoglobulins were found in patients with epilepsy treated with LTG or CBZ. As our group of patients consisted of otherwise healthy young adults, one should be especially aware of a possible effect of AEDs on immunoglobulin levels when treating selected patient groups, for example immunocompromised patients. Immunoglobulin concentrations should be measured in patients treated with LTG or CBZ who experience recurrent infections, and a change in medication should be considered. © 2012 John Wiley & Sons A/S. Source

Bramswig K.,Medical University of Vienna | Ploner F.,Medical University of Graz | Martel A.,Medical University of Vienna | Bauernhofer T.,Medical University of Graz | And 12 more authors.
Anti-Cancer Drugs | Year: 2014

Therapeutic options for patients with advanced pretreated soft tissue sarcomas are limited. However, in this setting, sorafenib has shown promising results. We reviewed the data of 33 patients with soft tissue sarcoma treated with sorafenib within a named patient program in Austria. Twelve physicians from eight different hospitals provided records for the analysis of data. Among the 33 patients, the predominant histological subtype of sarcoma was leiomyosarcoma (n=18, 55%). Other subtypes were represented by only one or two cases. Fifteen patients presented with metastases at the time of diagnosis. Another 17 patients developed metastases later in the course of the disease (data on one patient are missing). Most of the 33 patients had undergone resection of the primary (n=29, 88%) and half of the patients had received radiotherapy (n=17, 52%). Chemotherapy for metastatic disease had been administered to 30 patients (91%). The majority had received two or more regimens of chemotherapy (n=25, 76%) before sorafenib treatment. The use of sorafenib resulted in a median time to treatment failure of 92 days in patients with leiomyosarcoma and 45 days in patients with other histological subtypes. One-third of the patients derived benefits from treatment: four patients were documented with partial response and six with stabilized disease. In terms of treatment-related toxicity, skin problems of various degrees and gastrointestinal disturbances were frequently reported. In this retrospective analysis of heavily pretreated patients with advanced soft tissue sarcomas, sorafenib was associated with some antitumor activity and an acceptable toxicity profile. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Moser C.,University of Innsbruck | Zoderer D.,University of Innsbruck | Luef G.,University of Innsbruck | Rauchenzauner M.,Saint Vincent Hospital Zams | And 4 more authors.
Analytical and Bioanalytical Chemistry | Year: 2012

Co-administration of synthetic progestin containing hormonal contraceptives (HCs) and antiepileptic drugs (AEDs) is a common clinical situation which needs specific considerations due to drug interactions. Several studies have demonstrated that lamotrigine plasma levels are significantly decreased during co-medication with HCs, and that this interaction is associated with increased seizure frequency in most of the cases. Additionally, an increase in contraceptive failure and unintended pregnancy could be observed during comedication. Hence, monitoring of progestin plasma levels in patients with AED co-medication is of interest. A rapid and reliable online solid-phase extraction-high performance liquid chromatography-tandem mass spectrometry (online SPE-LC-MS/MS) method using gradient elution in the LC domain was established and validated for the simultaneous quantitative determination of gestodene, dienogest, drospirenone, etonogestrel, cyproterone acetate, and levonorgestrel in human plasma. The online SPE-LC-MS/MS method covered a quantification concentration range of 5-100 ng/ml for dienogest, 1-100 ng/ml for etonogestrel and 2-100 ng/ml for all other analytes. Stable isotope-labeled internal standards were used for analyte quantification based on selected reaction monitoring experiments. Inter- and intra-assay precision and accuracy were determined from quality control (QC) samples at the lower limits of quantification and at low, medium, and high concentration levels within the calibration range. Inter-assay reproducibility at the QC levels was better than 10% (relative standard deviation, RSD), accuracy at these levels ranged from -3.7% to 11.3%. Total extraction efficiency, tested at three concentrations, ranged from 92.5% to 106.4%. Matrix interferences were excluded by post-column infusion experiments. To prove the applicability of the assay in clinical cohorts, a sample set (n= 298) stemming from study patients under AED/oral HC comedication was screened for progestin plasma levels. This method has to be considered a research-use-only assay and must not be used for diagnostic or therapeutic purposes, since it did not undergo formal performance evaluation in the sense of the IVD directive (98/79/EG) of the European Community. © Springer-Verlag 2011. Source

Rauchenzauner M.,Saint Vincent Hospital Zams | Roscia S.,Innsbruck Medical University | Prieschl M.,Innsbruck Medical University | Wildt L.,Innsbruck Medical University | And 7 more authors.
Neuropediatrics | Year: 2014

Objectives Although previous studies suggest that valproate (VPA) may induce reproductive endocrine disorders, the effects of newer antiepileptic drugs (AEDs) on reproductive endocrine health have not been widely investigated and compared with those of older AEDs. Therefore, this multicenter cross-sectional study aimed to evaluate the prevalence of reproductive endocrine dysfunctions in pubertal females with epilepsy receiving VPA, lamotrigine (LTG), or levetiracetam (LEV) monotherapy. Patients and Methods Pubertal girls on VPA (n = 11), LTG (n = 8), or LEV (n = 13) monotherapy for at least 6 months were recruited. Healthy sex-matched and age-matched subjects were enrolled as controls (n = 32). Each participant underwent a comprehensive physical examination concerning signs of hyperandrogenism. The Ferriman-Gallwey score of hirsutism was assessed. In addition, all patients completed a standardized questionnaire regarding epilepsy, menstrual cycle, and hirsutism features. Adiposity indices were measured and weight gain was documented for each subject. Results Hirsutism score, occurrence of hyperandrogenism features, and adiposity indices were significantly higher in the VPA group when compared with LEV and control groups. VPA therapy was more frequently associated with weight gain when compared with LTG and controls, whereas no significant differences with regard to signs of hyperandrogenism were found between VPA and LTG groups. Furthermore, no differences in menstrual disorders were observed between groups. Conclusions Pubertal girls with epilepsy receiving VPA monotherapy were more likely to develop signs of hyperandrogenism, that is, hirsutism and acanthosis, than those on LEV or controls. However, no differences in occurrence of menstrual disorders and other reproductive dysfunctions were found between VPA, LTG, LEV, and control groups. These findings do not allow us to clearly determine whether or not VPA, LEV, and LTG monotherapies considerably affect reproductive endocrine health in pubertal girls with epilepsy. Therefore, further prospective studies of larger sample sizes are needed to establish if screening tests should be recommended. © 2014 Georg Thieme Verlag KG Stuttgart New York. Source

Rauchenzauner M.,Saint Vincent Hospital Zams | Ehrensberger M.,Innsbruck Medical University | Prieschl M.,Innsbruck Medical University | Kapelari K.,Innsbruck Medical University | And 5 more authors.
Journal of Neurology | Year: 2013

This study investigates the impact of generalized tonic-clonic seizures (GTCS) and antiepileptic drugs (AED) during pregnancy on gestational age (GA) and anthropometric data of newborns. One hundred twenty-nine singleton pregnancies resulting in live births from September 1999 to October 2010 in 106 women with epilepsy on AED therapy, recorded within the framework of the EURAP (International Registry of Antiepileptic Drugs and Pregnancy) program at the Department of Neurology, Medical University Innsbruck, Austria, were studied. Occurrence of ≥1 GTCS during pregnancy was associated with a shorter GA [median (range) 37.5 [35.1-41.6] vs. 39.7 [29.1-46.3] weeks; p ≤ 0.001], an overall five times higher preterm risk (p = 0.042) and a reduced birth weight in boys (2,900 [2,050-3,870] vs. 3,205 [1,575-4,355] g; p = 0.040). In primipara, when compared to multipara, GTCS ≥1 significantly reduced the GA (37.9 [35.1-41.6] vs. 39.7 [29.4-44.9] weeks; p = 0.020) and raised the incidence of low birth weight (LBW) (p = 0.022) in neonates. Antiepileptic drug polytherapy significantly increased the risk for small-for-gestational-age regarding weight (SGAW; p = 0.035) and regarding weight and/or length (SGA W/L; p = 0.046) when compared to monotherapy. GTCS during pregnancy was associated with diverse negative effects comprising shorter GA, an increased incidence of prematurity and LBW in primiparous women. Furthermore, AED polytherapy was correlated with an enhanced risk for SGA delivery. Re-evaluating the need for drug therapy (in particular polytherapy), maintaining seizure control for a given period before pregnancy and counseling about the importance of preventing GTCS might improve pregnancy outcome in women with epilepsy. © 2012 Springer-Verlag. Source

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