Successful treatment of a potentially fatal eastern brown snake (Pseudonaja textilis) envenomation in a dog with tiger-brown snake antivenom with serial quantification of venom antigen and antivenom concentrations in serum and urine.

CASE REPORT: A successfully treated case of eastern brown snake (Pseudonaja textilis) envenomation in a Jack Russel Terrier dog is described with measurement of venom and antivenom concentration pre- and post-treatment. Early presentation, prompt administration of tiger-brown snake antivenom, hospitalisation and critical care monitoring lead to low morbidity and rapid recovery from a potentially fatal envenomation. Retrospective measurement of urine and serum venom and antivenom provided insight into the potential severity of the case and rapid efficacy of antivenom. CLINICAL SIGNIFICANCE: Potentially fatal brown snakebite cases may initially present with only mild clinical signs despite having high concentrations of venom and potential for fatal outcome. Prompt treatment with antivenom is essential to prevent the development of progressive and fatal coagulopathy and paralysis.

Flavaglines target primitive leukemia cells and enhance anti-leukemia drug activity.

Identification of agents that target human leukemia stem cells is an important consideration for the development of new therapies. The present study demonstrates that rocaglamide and silvestrol, closely related natural products from the flavagline class of compounds, are able to preferentially kill functionally defined leukemia stem cells, while sparing normal stem and progenitor cells. In addition to efficacy as single agents, flavaglines sensitize leukemia cells to several anticancer compounds, including front-line chemotherapeutic drugs used to treat leukemia patients. Mechanistic studies indicate that flavaglines strongly inhibit protein synthesis, leading to the reduction of short-lived antiapoptotic proteins. Notably though, treatment with flavaglines, alone or in combination with other drugs, yields a much stronger cytotoxic activity toward leukemia cells than the translational inhibitor temsirolimus. These results indicate that the underlying cell death mechanism of flavaglines is more complex than simply inhibiting general protein translation. Global gene expression profiling and cell biological assays identified Myc inhibition and the disruption of mitochondrial integrity to be features of flavaglines, which we propose contribute to their efficacy in targeting leukemia cells. Taken together, these findings indicate that rocaglamide and silvestrol are distinct from clinically available translational inhibitors and represent promising candidates for the treatment of leukemia.

Managing medical malpractice risk via system science.

The complexity of health care is increasing at an alarming rate. Medical malpractice risks, which are inherent elements of this complexity, threaten the survival of both physicians and hospitals. Technological advances, social concerns, legal ramifications, economic values, and political pressures all amplify risk for health care professionals. Federal government warnings to control health care costs compound the dilemma. System science provides a framework for identifying, analyzing, and ranking all types of risk so that they can be balanced against the more easily recognized benefits of health care. Rather than limiting the concept of risk management to the traditional concern for financial loss, this paper stresses a much broader scope of risk assessment and control. All medical activities that can lead to injury or death of any person, or damage to or loss of property, material, or reputation must be systematically managed regarding risk. A strong theoretical foundation is combined with the successful application of system science to managing risk at the Saint Joseph Medical Center in Burbank, California.