Chlorprothixene in Bodies After Exhumation.

Chlorprothixene in bodies after exhumation.

Forensic Sci Int. 2013 Jun 10; 229(1-3): e30-4
Käferstein H, Sticht G, Madea B

Toxicological analyses on body tissues and interpretation of results after exhumation are a challenging task. We report five cases in which toxicological analyses had to be performed due to suspicion of homicide by chlorprothixene intoxication. Exhumations had to be carried out following post mortem intervals in earth graves between two and five and a half years. Chlorprothixene and in some cases also its metabolites could be detected in liver and brain. For the interpretation of the results, chlorprothixene concentrations determined in brain should be used because of a relative isolation of the brain within the skull. However, a loss of organ weights due to post mortem degradation, which may lead to an increase of drug levels, should be taken into account. HubMed – drug

Effects of Risperidone and Olanzapine Dose Reduction on Cognitive Function in Stable Patients With Schizophrenia: An Open-Label, Randomized, Controlled, Pilot Study.

Schizophr Bull. 2013 Jul 1;
Takeuchi H, Suzuki T, Remington G, Bies RR, Abe T, Graff-Guerrero A, Watanabe K, Mimura M, Uchida H

Impact of dose reduction of atypical antipsychotics on cognitive function has not been investigated in stable patients with schizophrenia. In this open-label, 28-week, randomized controlled trial, stable patients with schizophrenia treated with risperidone or olanzapine were randomly assigned to the reduction group (dose reduced by 50% in 4 weeks and then maintained) or maintenance group (dose kept constant). Assessments at baseline and week 28 included the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Positive and Negative Syndrome Scale (PANSS), and Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). Sixty-one patients were enrolled; 2 of 31 (6.5%) and 5 of 30 (16.7%) patients prematurely withdrew from the study in the reduction and maintenance groups, respectively. While no significant differences in change in the PANSS total score were observed between the 2 groups, the reduction group showed significantly greater improvements in the RBANS and DIEPSS total scores compared with the maintenance group (mean ± SD, +7.0±7.1 vs -0.1±8.0, P < .001; -0.9±1.7 vs +0.1±1.2, P = .010, respectively). This 6-month pilot study suggests that risperidone or olanzapine dose reduction of 50% can improve cognitive function for stable patients with schizophrenia. Due to the open-label design, small sample size, and short study duration, however, there is a need to confirm the finding through double-blind, larger scale trials with longer follow-up periods. Moreover, potential risks of relapse following antipsychotic dose reduction should be thoroughly investigated in longer term studies. HubMed – drug

Growth of Nasal-Laryngeal Airways in Children and Their Implications in Breathing and Inhaled Aerosol Dynamics.

Respir Care. 2013 Jul 2;
Xi J, Si X, Zhou Y, Kim J, Berlinski A

The human respiratory airway undergoes dramatic growth during infancy and childhood, which induces significant variability in airflow pattern and particle depositions. However, deposition studies have typically focused on adult subjects, results of which may not be readily extrapolated to children.To quantify the growth of human nasal-laryngeal airways at early ages, and to evaluate its impact on breathing resistance and respirable aerosol deposition.Four image-based nasal-laryngeal models were developed from children of different ages (10-day to 5-year old) and were compared to that of an adult. The airway dimensions were quantified in terms of different parameters (volume, cross-section area, and hydraulic diameter) and of different anatomies (nose, pharynx, and larynx). Breathing resistance and aerosol deposition were computed using a high-fidelity fluid-particle transport model and validated against in vitro measurements in replica casts fabricated from the same airway models.Significant differences in nasal anatomy were observed among the five subjects in both morphology and dimension. The turbinate region appeared to experience the most noticeable growth during the first five years of age. The nasal airway volumes of the 10-day, 7-month, 3-year, and 5-year old subjects were 6.4%, 18.8%, 24.2% and 40.3% that of the adult, respectively. Remarkable inter-group variability was observed in airflow, pressure drop, deposition fraction, and particle accumulation. The CFD predicted pressure drops and deposition fractions were in close agreement with in vitro measurements.Age effects are significant in both breathing resistance and micrometer particle deposition. The image-CFD coupled method provides an efficient and effective approach in understanding patient-specific airflows and particle deposition, which have important implications in pediatric inhalation drug delivery and respiratory disorder diagnosis. HubMed – drug

A Preclinical Evaluation of Neural Stem Cell-Based Cell Carrier for Targeted Antiglioma Oncolytic Virotherapy.

J Natl Cancer Inst. 2013 Jul 3; 105(13): 968-977
Ahmed AU, Thaci B, Tobias AL, Auffinger B, Zhang L, Cheng Y, Kim CK, Yunis C, Han Y, Alexiades NG, Fan X, Aboody KS, Lesniak MS

Oncolytic adenoviral virotherapy (OV) is a highly promising approach for the treatment of glioblastoma multiforme (GBM). In practice, however, the approach is limited by poor viral distribution and spread throughout the tumor mass.To enhance viral delivery, replication, and spread, we used a US Food and Drug Administration-approved neural stem cell line (NSC), HB1.F3.CD, which is currently employed in human clinical trials. HB1.F3.CD cells were loaded with an oncolytic adenovirus, CRAd-Survivin-pk7, and mice bearing various human-derived GBMs were assessed with regard to NSC migration, viral replication, and therapeutic efficacy. Survival curves were evaluated with Kaplan-Meier methods. All statistical tests were two-sided.Antiglioma activity of OV-loaded HB1.F3.CD cells was effective against clinically relevant human-derived glioma models as well as a glioma stem cell-enriched xenograft model. Median survival was prolonged by 34% to 50% compared with mice treated with OV alone (GBM43FL model median survival = 19.5 days, OV alone vs NSC + OV, hazard ratio of survival = 2.26, 95% confidence interval [CI] = 1.21 to 12.23, P = .02; GBM12 model median survival = 43.5 days, OV alone vs NSC + OV, hazard ratio of survival = 2.53, 95% CI = 1.21 to 10.38, P = .02). OV-loaded HB1.F3.CD cells were shown to effectively migrate to the contralateral hemisphere and hand off the therapeutic payload of OV to targeted glioma cells. In vivo distribution and migratory kinetics of the OV-loaded HB1.F3.CD cells were successfully monitored in real time by magnetic resonance imaging. OV-loaded NSCs retained their differentiation fate and were nontumorigenic in vivo.HB1.F3.CD NSCs loaded with CRAd-Survivin-pk7 overcome major limitations of OV in vivo and warrant translation in a phase I human clinical trial for patients with GBM. HubMed – drug