Faculty Bibliography

BACKGROUND: Agents of opportunity (AO) are potentially harmful biological, chemical, radiological, and pharmaceutical substances commonly used for health care delivery and research. AOs are present in all academic medical centers (AMC), creating vulnerability in the health care sector; AO attributes and dissemination methods likely predict risk; and AMCs are inadequately secured against a purposeful AO dissemination, with limited budgets and competing priorities. We explored health care workers' perceptions of AMC security and the impact of those perceptions on AO risk. METHODS: Qualitative methods (survey, interviews, and workshops) were used to collect opinions from staff working in a medical school and 4 AMC-affiliated hospitals concerning AOs and the risk to hospital infrastructure associated with their uncontrolled presence. Secondary to this goal, staff perception concerning security, or opinions about security behaviors of others, were extracted, analyzed, and grouped into themes. RESULTS: We provide a framework for depicting the interaction of staff behavior and access control engineering, including the tendency of staff to 'defeat' inconvenient access controls. In addition, 8 security themes emerged: staff security behavior is a significant source of AO risk; the wide range of opinions about 'open' front-door policies among AMC staff illustrates a disparity of perceptions about the need for security; interviewees expressed profound skepticism concerning the effectiveness of front-door access controls; an AO risk assessment requires reconsideration of the security levels historically assigned to areas such as the loading dock and central distribution sites, where many AOs are delivered and may remain unattended for substantial periods of time; researchers' view of AMC security is influenced by the ongoing debate within the scientific community about the wisdom of engaging in bioterrorism research; there was no agreement about which areas of the AMC should be subject to stronger access controls; security personnel play dual roles of security and customer service, creating the negative perception that neither role is done well; and budget was described as an important factor in explaining the state of security controls. CONCLUSIONS: We determined that AMCs seeking to reduce AO risk should assess their institutionally unique AO risks, understand staff security perceptions, and install access controls that are responsive to the staff's tendency to defeat them. The development of AO attribute fact sheets is desirable for AO risk assessment; new funding and administrative or legislative tools to improve AMC security are required; and security practices and methods that are convenient and effective should be engineered

OBJECTIVE: To develop and apply a novel modeling approach to support medical and public health disaster planning and response using a sarin release scenario in a metropolitan environment. METHODS: An agent-based disaster simulation model was developed incorporating the principles of dose response, surge response, and psychosocial characteristics superimposed on topographically accurate geographic information system architecture. The modeling scenarios involved passive and active releases of sarin in multiple transportation hubs in a metropolitan city. Parameters evaluated included emergency medical services, hospital surge capacity (including implementation of disaster plan), and behavioral and psychosocial characteristics of the victims. RESULTS: In passive sarin release scenarios of 5 to 15 L, mortality increased nonlinearly from 0.13% to 8.69%, reaching 55.4% with active dispersion, reflecting higher initial doses. Cumulative mortality rates from releases in 1 to 3 major transportation hubs similarly increased nonlinearly as a function of dose and systemic stress. The increase in mortality rate was most pronounced in the 80% to 100% emergency department occupancy range, analogous to the previously observed queuing phenomenon. Effective implementation of hospital disaster plans decreased mortality and injury severity. Decreasing ambulance response time and increasing available responding units reduced mortality among potentially salvageable patients. Adverse psychosocial characteristics (excess worry and low compliance) increased demands on health care resources. Transfer to alternative urban sites was possible. CONCLUSIONS: An agent-based modeling approach provides a mechanism to assess complex individual and systemwide effects in rare events.

We report a case of multisystem organ failure after large volume subcutaneous injection of castor oil for cosmetic enhancement. An unlicensed practitioner injected 500 mL of castor oil bilaterally to the hips and buttocks of a 28-year-old male to female transsexual. Immediate local pain and erythema were followed by abdominal and chest pain, emesis, headache, hematuria, jaundice, and tinnitus. She presented to an emergency department 12 hours postinjection. Persistently hemolyzed blood samples complicated preliminary laboratory analysis. She rapidly deteriorated despite treatment and developed fever, tachycardia, hemolysis, thrombocytopenia, hepatitis, respiratory distress, and anuric renal failure. An infectious diseases evaluation was negative. After intensive supportive care, including mechanical ventilation and hemodialysis, she was discharged 11 days later, requiring dialysis for an additional 1.5 months. Castor oil absorption was inferred from recovery of the Ricinus communis biomarker, ricinine, in the patient's urine (41 ng/mL). Clinicians should anticipate multiple complications after unapproved methods of cosmetic enhancement

Chiral substances possess a unique architecture such that, despite sharing identical molecular formulas, atom-to-atom linkages, and bonding distances, they cannot be superimposed. Thus, in the environment of living systems, where specific structure-activity relationships may be required for effect (e.g., enzymes, receptors, transporters, and DNA), the physiochemical and biochemical properties of racemic mixtures and individual stereoisomers can differ significantly. In drug development, enantiomeric selection to maximize clinical effects or mitigate drug toxicity has yielded both success and failure. Further complicating genetic polymorphisms in drug disposition, stereoselective metabolism of chiral compounds can additionally influence pharmacokinetics, pharmacodynamics, and toxicity. Optically pure pharmaceuticals may undergo racemization in vivo, negating single enantiomer benefits or inducing unexpected effects. Appropriate chiral antidotes must be selected for therapeutic benefit and to minimize adverse events. Enantiomers may possess different carcinogenicity and teratogenicity. Environmental toxicology provides several examples in which compound bioaccumulation, persistence, and toxicity show chiral dependence. In forensic toxicology, chiral analysis has been applied to illicit drug preparations and biological specimens, with the potential to assist in determination of cause of death and aid in the correct interpretation of substance abuse and 'doping' screens. Adrenergic agonists and antagonist, nonsteroidal anti-inflammatory agents, SSRIs, opioids, warfarin, valproate, thalidomide, retinoic acid, N-acetylcysteine, carnitine, penicillamine, leucovorin, glucarpidase, pesticides, polychlorinated biphenyls, phenylethylamines, and additional compounds will be discussed to illustrate important concepts in 'chiral toxicology.'

Ingestion of immature, environmentally stressed, or cultivar-specific Solanum species (particularly the potato) has been previously associated with gastrointestinal and neurological symptoms caused by solanaceous steroidal glycoalkaloids (SGAs). We report on two geographically, temporally disparate outbreaks of poisoning by susumber berries (Solanum torvum- Solanaceae) and on detection of alkaloids not present in non-toxic berries. Five family members in New York City participated in a traditional evening meal containing Jamaican susumber berries. All those consuming berries were symptomatic the following morning with varying degrees of gastrointestinal distress, dizziness, slurred speech, cranial nerve deficits, and ataxia. The most seriously afflicted patient developed hypertension, confusion, proximal upper extremity weakness, and hypercapnic respiratory failure requiring prolonged mechanical ventilation. A separate cohort of six patients in Toronto ate unripe Jamaican susumber berries. They presented 14h post-ingestion with varying degrees of diarrhea, weakness, facial paralysis, slurred speech, ataxia, early hypertension, and proximal weakness. Two patients had ventilatory decompensation; one required intubation. Poisonous berries appeared indistinguishable from non-toxic varieties. We isolated solasonine, larger amounts of solamargine, and other steroidal glycoalkaloids in the toxic berry strains. S. torvum poisoning can produce significant neurological and gastrointestinal effects which appear to be mediated by SGAs present in the berries

INTRODUCTION: Compared to other calcium channel blockers (CCBs), overdose with dihydropyridine CCBs are considered relatively benign due to their vascular selectivity. Although not a sustained-release preparation, amlodipine's prolonged duration of effect is concerning following overdose. In addition, angiotensin II receptor blocker blunting of vasoconstrictive and sympathetic compensatory responses could exacerbate calcium channel blocker toxicity. We describe severe toxicity associated with an overdose of amlodipine and valsartan. CASE REPORT: A 75-year-old woman presented to the ED 45 minutes after a witnessed suicidal ingestion of a 'handful' of amlodipine and valsartan tablets. Hypotension, which appeared two hours after ingestion, was refractory to crystalloids and colloids, calcium gluconate, epinephrine, norepinephrine, phenylephrine, and vasopressin infusions. High-dose insulin euglycemia (HIE) therapy, and treatment with glucagon and naloxone were successful in improving her hemodynamic status. In this combined overdose, right heart catheterization demonstrated both negative inotropic effects and decreased systemic vascular resistance. CONCLUSION: Co-ingestion of amlodipine with valsartan produced profound toxicity. Early institution of HIE therapy may be beneficial to reverse these effects

A 10-year-old boy (37.5 kg; body surface area 1.26m2) with osteosarcoma of the right humerus received a planned 4-hour infusion of high-dose methotrexate (16 g, 12.7 g/m(2)). His previous medical history was notable for an implanted central venous catheter placement complicated by Horner's syndrome. Renal and hepatic functions were normal at baseline. A postinfusion methotrexate concentration was uninterpretable, but the significance of this result was not initially appreciated by the treating clinicians. Over the next 48 hours, the child developed blurry vision, painful mucositis, stomatitis, and facial blistering. Reported vital signs were: BP, 121/82 mm Hg; pulse, 111/minute; respirations, 16/minute. A physical examination was consistent with the reported symptoms. The 48-hour postinfusion serum methotrexate concentration at the time of poison control center (PCC) consultation was 171 micromol/L