Hypoglycemia and Sudden Death During Treatment With Methadone for Opiate Detoxification.

CLINICAL FEATURES: We present a case of a middle-aged man admitted to an inpatient detoxification facility for withdrawal of intranasal heroin, alprazolam, and ethanol. The patient was placed on methadone and chlordiazepoxide tapers. Ondansetron and trazodone were prescribed as needed for symptom control. On the third hospital day, the patient was found unresponsive with blood glucose of 40 mg/dL. He had no history of glucose dysregulation. The patient was pronounced dead shortly thereafter. Methadone overdose was ruled the cause of death. THERAPEUTIC CHALLENGES: There have been studies linking methadone with glucose dysregulation. Hypoglycemia can induce changes in the electrical system in the heart, including lengthening QT interval, lengthening repolarization, and causing ST wave changes. In addition, there have been studies linking methadone treatment to QT interval prolongation and torsade de pointes. Ondansetron and trazodone have both been associated with cardiac conduction abnormalities. SOLUTION: We recommend initial blood glucose and cardiac monitoring in patients taking methadone 40 mg daily or higher.

Increasing Awareness on Health Care Access in Florida: A Community-Based Medical-Legal Practicum Project.

PROBLEM: Service learning and experiential coursework has become a requirement for medical students and law students. Advocacy for the underinsured and uninsured is of ethical importance to both the practice of law and medicine, however engaging professional students in meaningful advocacy work with community partners can be challenging. PURPOSE: The article describes a partnership between medical and law students in a community-based service learning project to promote health care access. KEY POINTS: Law and medical students at Florida International University partnered with community members and Florida Legal Services to collect patient narratives, disseminate information on Medicaid expansion to community members, and present patient stories to state lawmakers. CONCLUSIONS: The medical and law students learned about each other's professional roles and gained skills in interviewing, and legislative and policy advocacy through this service learning project by providing legislative testimony to key stakeholders and community education on Medicaid expansion.

Dynamics-Based Discovery of Allosteric Inhibitors: Selection of New Ligands for the C-terminal Domain of Hsp90.

The study of allosteric functional modulation in dynamic proteins is attracting increasing attention. In particular, the discovery of new allosteric sites may generate novel opportunities and strategies for drug development, overcoming the limits of classical active-site oriented drug design. In this paper, we report on the results of a novel, ab initio, fully computational approach for the discovery of allosteric inhibitors based on the physical characterization of signal propagation mechanisms in proteins and apply it to the important molecular chaperone Hsp90. We first characterize the allosteric "hot spots" involved in interdomain communication pathways from the nucleotide-binding site in the N-domain to the distal C-domain. On this basis, we develop dynamic pharmacophore models to screen drug libraries in the search for small molecules with the functional and conformational properties necessary to bind these "hot spot" allosteric sites. Experimental tests show that the selected moelcules bind the Hsp90 C-domain, exhibit antiproliferative activity in different tumor cell lines, while not affecting proliferation of normal human cells, destabilize Hsp90 client proteins, and disrupt association with several cochaperones known to bind the N- and M-domains of Hsp90. These results prove that the hits alter Hsp90 function by affecting its conformational dynamics and recognition properties through an allosteric mechanism. These findings provide us with new insights on the discovery and development of new allosteric inhibitors that are active on important cellular pathways through computational biology. Though based on the specific case of Hsp90, our approach is general and can readily be extended to other target proteins and pathways.