Implementing a randomized clinical trial on a pediatric psychiatric inpatient unit at a children's hospital: the case of clonidine for post-traumatic stress.

Randomized clinical trials (RCTs) of psychotropic medications are uncommon among child and adolescent populations, and even rarer on pediatric, psychiatric inpatient units. We mention some of these studies, and then discuss the advantages and challenges of conducting a RCT among youngsters on an inpatient psychiatric unit in a pediatric hospital, using as an example our ongoing study of clonidine for intrusive symptoms of post-traumatic stress. Our purpose is to alert potential investigators to the obstacles they may encounter while implementing a RCT, while also pointing the way to potential resources. Advantages of inpatient units for RCTs include easy access to patients, with the potential for careful monitoring of both patients' clinical status and of medication administration. Challenges include the need for the psychiatric researcher to form liaison with other important areas within the hospital, such as the Institutional Review Board, the Pharmacy, and sometimes a General Clinical Research Center and a Clinical Research Program. The functions of these departments are discussed, and additional support for clinicians in hospital settings without these departments is described. Other issues include training clinical nurses to conduct research while making adequate provisions for their time to do so. Attitudes on a clinical psychiatric inpatient unit toward research also merit consideration. Furthermore, as with any study in a hospital setting, recruitment presents its own set of challenges. Finally, one must be cognizant of how clinical information flows between clinicians and researchers.

3-Amino-2-hydroxyamides and related compounds as inhibitors of methionine aminopeptidase-2.

Substituted 3-amino-2-hydroxyamides and related hydroxyamides and acylhydrazines were identified as inhibitors of human methionine aminopeptidase-2 (MetAP2). Examination of substituents through parallel synthesis and iterative structure-based design allowed the identification of potent inhibitors with good selectivity against MetAP1. Diacylhydrazine 3t (A-357300) was identified as an analogue displaying inhibition of methionine processing and cellular proliferation in human microvascular endothelial cells (HMVEC).

Novel inhibitors of bacterial protein synthesis: structure-activity relationships for 1,8-naphthyridine derivatives incorporating position 3 and 4 variants.

Structure-activity relationships for a recently discovered novel ribosome inhibitor (NRI) class of antibacterials were investigated. Preliminary efforts to optimize protein synthesis inhibitory activity of the series through modification of positions 3 and 4 of the naphthyridone lead template resulted in the identification of several biochemically potent analogues. A lack of corresponding whole cell antibacterial activity is thought to be a consequence of poor cellular penetration as evidenced by the enhancement of activity observed for a lead analogue tested in the presence of a cell permeabilizing agent.