BACKGROUND:This study compared the efficacy and safety of 4 therapeutically relevant strategies for switching clinically stable patients from a conventional antipsychotic drug or risperidone to olanzapine.METHOD:Two hundred nine outpatients with a DSM-IV diagnosis of schizophrenia or schizo-affective disorder who were clinically stable while being treated with a conventional antipsychotic drug or risperidone were openly randomly assigned to either abrupt or gradual discontinuation of their prior antipsychotic drug. Patients were further randomly assigned in a double-blind fashion to immediate olanzapine initiation (olanzapine, 10 mg q.d. for 3 weeks) or stepwise initiation (a sequence of 1 week each on placebo; olanzapine, 5 mg q.d.; and olanzapine, 10 mg q.d.). The efficacy of these 4 switching paradigms was assessed using the Clinical Global Impressions (CGI)-Improvement scale, Patient's Global Impressions (PGI)-Improvement scale, and Positive and Negative Syndrome Scale (PANSS). Safety assessments included ratings for extrapyramidal symptoms, cognitive impairment, adverse events, laboratory parameters, weight change, and vital signs.RESULTS:The paradigm of gradual antipsychotic drug discontinuation combined with an initial full dose of olanzapine, 10 mg/day, had the most favorable efficacy and tolerability profile overall. By week 3, the majority of completing patients on all 4 switching paradigms were either improved or clinically unchanged (> 90%). No clinically significant differences between switching paradigms were seen in laboratory values or vital signs.CONCLUSION:In this study, switching clinically stable outpatients with a diagnosis of schizophrenia or schizoaffective disorder to olanzapine was most successful when a full therapeutic dose of olanzapine was immediately initiated while gradually discontinuing prior conventional antipsychotic drug or risperidone treatment. Overall, switching was achieved without increased vulnerability to relapse or to occurrence of clinically burdensome antipsychotic drug withdrawal symptoms in the majority of patients.

Recent evidence suggests that controlled reasoning processes play an important role in cue competition in human causal learning (see De Houwer, J., Beckers, T., & Vandorpe, S. (2005). Evidence for the role of higher-order reasoning processes in cue competition and other learning phenomena. Learning &Behavior, 33(2), 239–249, for a review). Until now, this evidence comes almost exclusively from studies with simple designs that involved only a limited number of cues. Little is known about the role of controlled reasoning processes when the design is more complex. It is important to examine this issue because the complexity of the design could determine the resources that are available for reasoning and thus the role that reasoning plays in cue competition. We directly compared cue competition in a simple and a complex design. The results showed that complexity of the design affected retrospective cue competition but not forward cue competition. More fine grained analyses with respect to retrospective cue competition showed that unovershadowing but not backward blocking differed significantly between complexity conditions.

The potential of RNAs and RNA–protein (RNP) complexes as drug targets is currently being explored in various investigations. For example, a hexa-arginine derivative of neomycin (NeoR) and a tri-arginine derivative of gentamicin (R3G) were recently shown to disrupt essential RNP interactions between the trans-activator protein (Tat) and the Tat-responsive RNA (trans-activating region) in the human immunodeficiency virus (HIV) and also inhibit HIV replication in cell culture. Based on certain structural similarities, we postulated that NeoR and R3G might also be effective in disrupting RNP interactions and thereby inhibiting bacterial RNase P, an essential RNP complex involved in tRNA maturation. Our results indicate that indeed both NeoR and R3G inhibit RNase P activity from evolutionarily divergent pathogenic bacteria and do so more effectively than they inhibit partially purified human RNase P activity.

Annals of the New York Academy of SciencesVolume 616, Issue 1 p. 563-565 Stable Transformed Human Cell Lines Exhibiting tat-Directed Expression of Tissue Plasminogen Activator S. K. MALCOLM, S. K. MALCOLM Departments of Molecular Biology and Virology Research Lilly Research Laboratories Indianapolis, Indiana 46285Search for more papers by this authorT. W. THAIS, T. W. THAIS Departments of Molecular Biology and Virology Research Lilly Research Laboratories Indianapolis, Indiana 46285Search for more papers by this authorP. A. HEFFERNAN, P. A. HEFFERNAN Departments of Molecular Biology and Virology Research Lilly Research Laboratories Indianapolis, Indiana 46285Search for more papers by this authorS. R. JASKUNAS, S. R. JASKUNAS Departments of Molecular Biology and Virology Research Lilly Research Laboratories Indianapolis, Indiana 46285Search for more papers by this authorJ. TANG, J. TANG Departments of Molecular Biology and Virology Research Lilly Research Laboratories Indianapolis, Indiana 46285Search for more papers by this authorJ. M. COLACINO, J. M. COLACINO Departments of Molecular Biology and Virology Research Lilly Research Laboratories Indianapolis, Indiana 46285Search for more papers by this authorB. R. WARREN, B. R. WARREN Departments of Molecular Biology and Virology Research Lilly Research Laboratories Indianapolis, Indiana 46285Search for more papers by this author S. K. MALCOLM, S. K. MALCOLM Departments of Molecular Biology and Virology Research Lilly Research Laboratories Indianapolis, Indiana 46285Search for more papers by this authorT. W. THAIS, T. W. THAIS Departments of Molecular Biology and Virology Research Lilly Research Laboratories Indianapolis, Indiana 46285Search for more papers by this authorP. A. HEFFERNAN, P. A. HEFFERNAN Departments of Molecular Biology and Virology Research Lilly Research Laboratories Indianapolis, Indiana 46285Search for more papers by this authorS. R. JASKUNAS, S. R. JASKUNAS Departments of Molecular Biology and Virology Research Lilly Research Laboratories Indianapolis, Indiana 46285Search for more papers by this authorJ. TANG, J. TANG Departments of Molecular Biology and Virology Research Lilly Research Laboratories Indianapolis, Indiana 46285Search for more papers by this authorJ. M. COLACINO, J. M. COLACINO Departments of Molecular Biology and Virology Research Lilly Research Laboratories Indianapolis, Indiana 46285Search for more papers by this authorB. R. WARREN, B. R. WARREN Departments of Molecular Biology and Virology Research Lilly Research Laboratories Indianapolis, Indiana 46285Search for more papers by this author First published: December 1990 https://doi.org/10.1111/j.1749-6632.1990.tb17894.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume616, Issue1AIDS: Anti-HIV Agents, Therapies, and VaccinesDecember 1990Pages 563-565 RelatedInformation