Michael S. Bronze

Microbiological, Biological, and Chemical Weapons of Warfare and Terrorism

&NA; Microbiological, biological, and chemical toxins have been employed in warfare and in terrorist attacks. In this era, it is imperative that health care providers are familiar with illnesses caused by these agents. Botulinum toxin produces a descending flaccid paralysis. Staphylococcal enterotoxin B produces a syndrome of fever, nausea, and diarrhea and may produce a pulmonary syndrome if aerosolized. Clostridium perfringens ∈‐toxin could possibly be aerosolized to produce acute pulmonary edema. Ricin intoxication can manifest as gastrointestinal hemorrhage after ingestion, severe muscle necrosis after intramuscular injection, and acute pulmonary disease after inhalation. Nerve agents inhibit acetylcholinesterase and thus produce symptoms of increased cholinergic activity. Ammonia, chlorine, vinyl chloride, phosgene, sulfur dioxide, and nitrogen dioxide, tear gas, and zinc chloride primarily injure the upper respiratory tract and the lungs. Sulfur mustard (and nitrogen mustard) are vesicant and alkylating agents. Cyanide poisoning ranges from suddenonset headache and drowsiness to severe hypoxemia, cardiovascular collapse, and death. Health care providers should be familiar with the medical consequences of toxin exposure, and understand the pathophysiology and management of resulting illness.

Listeria monocytogenes : epidemiology, human disease, and mechanisms of brain invasion

Listeria monocytogenes is a facultative intracellular bacterium that has predilection for causing central nervous systemic infections in humans and domesticated animals. This pathogen can be found worldwide in the food supply and most L. monocytogenes infections are acquired through ingestion of contaminated food. The main clinical syndromes caused by L. monocytogenes include febrile gastroenteritis, perinatal infection, and systemic infections marked by central nervous system infections with or without bacteremia. Experimental infection of mice has been used for over 50 years as a model system to study the pathogenesis of this organism including the mechanisms by which it invades the brain. Data from this model indicate that a specific subset of monocytes, distinguished in part by high expression of the Ly-6C antigen, become parasitized in the bone marrow and have a key role in transporting intracellular bacteria across the blood-brain barriers and into the central nervous system. This Minireview will summarize recent epidemiologic and clinical information regarding L. monocytogenes as a human pathogen and will discuss current in vitro and in vivo data relevant to the role of parasitized monocytes and the pathogenetic mechanisms that underlie its formidable ability to invade the central nervous system.

Osteoporosis in inflammatory bowel disease.

Osteoporosis commonly afflicts patients with inflammatory bowel disease, and many factors link the 2 states together. A literature review was conducted about the pathophysiology of osteoporosis in relation to inflammatory bowel disease. Screening guidelines for osteoporosis in general as well as those directed at patients with inflammatory bowel disease are reviewed, as are currently available treatment options. The purpose of this article is to increase physician awareness about osteopenia and osteoporosis occurring in patients with inflammatory bowel disease and to provide basic, clinically relevant information about the pathophysiology and guidelines to help them treat these patients in a cost-effective manner.

Bacterial pathogens as biological weapons and agents of bioterrorism.

&NA; Bacterial pathogens have been identified as agents that have been, or could be, used as weapons of biological warfare and/or biological terrorism. These agents are relatively easily obtained, prepared, and dispersed, either as weapons of mass destruction or for more limited terrorist attacks. Although phylogenetically diverse, these agents all have the potential for aerosol dissemination. Physicians in the United States and most of the developed world have never encountered most of these agents and the diseases they produce. Public health programs must be prepared, and individual primary care providers must be able to recognize, diagnose, treat, and prevent infection with these agents.

Competency-Based Education and Training in Internal Medicine

Recent efforts to improve medical education include adopting a new framework based on 6 broad competencies defined by the Accreditation Council for Graduate Medical Education. In this article, the Alliance for Academic Internal Medicine Education Redesign Task Force II examines the advantages and challenges of a competency-based educational framework for medical residents. Efforts to refine specific competencies by developing detailed milestones are described, and examples of training program initiatives using a competency-based approach are presented. Meeting the challenges of a competency-based framework and supporting these educational innovations require a robust faculty development program. Challenges to competency-based education include teaching and evaluating the competencies related to practice-based learning and improvement and systems-based practice, as well as implementing a flexible time frame to achieve competencies. However, the Alliance for Academic Internal Medicine Education Redesign Task Force II does not favor reducing internal medicine training to less than 36 months as part of competency-based education. Rather, the 36-month time frame should allow for remediation to address deficiencies in achieving competencies and for diverse enrichment experiences in such areas as quality of care and practice improvement for residents who have demonstrated skills in all required competencies.

Clinical use of anti-TNF therapy and increased risk of infections

Biologics such as antitumor necrosis factor (anti-TNF) drugs have emerged as important agents in the treatment of many chronic inflammatory diseases, especially in cases refractory to conventional treatment modalities. However, opportunistic infections have become a major safety concern in patients on anti-TNF therapy, and physicians who utilize these agents must understand the increased risks of infection. A literature review of the published data on the risk of bacterial, viral, fungal, and parasitic infections associated with anti-TNF therapy was performed and the clinical presentation, diagnostic tests, management, and prevention of opportunistic infections in patients receiving anti-TNF therapy were reviewed. Awareness of the therapeutic potential and associated adverse events is necessary for maximizing therapeutic benefits while minimizing adverse effects from anti-TNF treatments. Patients should be adequately vaccinated when possible and closely monitored for early signs of infection. When serious infections occur, withdrawal of anti-TNF therapy may be necessary until the infection has been identified and properly treated.

Osteonecrosis Complicating Highly Active Antiretroviral Therapy in Patients Infected with Human Immunodeficiency Virus

Few patients with osteonecrosis that complicates human immunodeficiency virus (HIV) infection have been reported. We describe 5 patients whose symptoms of osteonecrosis developed with viral suppression and improvement in CD4 lymphocyte counts as a result of antiretroviral therapy. In addition, we review previously reported cases. The mean patient age was 35 years, and HIV was the sole risk factor in only 33%. Eighteen patients (55%) were receiving antiretroviral treatment when osteonecrosis was diagnosed. For 16 patients whose CD4 lymphocyte counts were reported, the mean CD4 count was 350 cells/mm(3). In 10 of these patients, the occurrence or worsening of symptoms of osteonecrosis appeared to be related to successful antiretroviral therapy. We conclude that osteonecrosis is an emerging manifestation of HIV infection and that it may be either a consequence of immunologic and virologic improvement resulting from antiretroviral therapy or a complication caused by the drugs themselves.

The Reemergence of Serious Group A Streptococcal Infections and Acute Rheumatic Fever

Acute rheumatic fever and life-threatening group A streptococcal infections have reemerged during the past 15 years to once again become a serious health threat in the developed countries of the world. Reports of outbreaks of acute rheumatic fever in many parts of this country and others have shattered the complacency that the health-care community had acquired related to this devastating sequela of streptococcal pharyngitis. Invasive streptococcal infections, often associated with loss of limbs of life despite optimal antibiotic therapy, have underscored the potential virulence of these organisms. A new clinical entity, streptococcal toxic shock syndrome, has emerged as a consequence of the new invasive strains of group A streptococci. In this article, the authors summarize the recent changes in the epidemiology of group A streptococcal infections and rheumatic fever and review the potential reasons for the increased virulence of these organisms. In addition, they discuss prospects for a streptococcal M protein vaccine designed to control these infections and their sequelae.

Lipoteichoic acid and M protein: dual adhesins of group A streptococci

The roles of lipoteichoic acid (LTA) and M protein in the adherence of group A streptococci to human cells were investigated. Both M+ and M- streptococci bound to pharyngeal and buccal epithelial cells in similar numbers. Streptococcal attachment was inhibited by LTA, but not by the pepsin-extracted, amino-terminal half of M protein (pep M), suggesting that M protein does not mediate attachment to these cells. However, a purified, recombinant, intact M protein did block attachment of streptococci to buccal cells. Using synthetic peptides, the inhibitory domain was localized to a region of intact M protein that is within or near the bacterial cell wall. Evidence is presented to suggest that on the surface of streptococci this region of the M protein is probably not accessible for interactions with host cell receptors and that M protein does not mediate attachment to buccal or pharyngeal cells. In contrast, approximately 10-times more M+ streptococci bound to Hep-2 cells than did M- streptococci and pep M protein blocked binding of streptococci to Hep-2 cells. The data suggest that at least two streptococcal adhesins, LTA and M protein, are involved in the adherence of streptococci to certain cells and that the relative contributions of these adhesins to the attachment process depends on the type of host cells used to study adherence.

Viral Agents as Biological Weapons and Agents of Bioterrorism

Multiple viral agents have been classified by the CDC as potential weapons of mass destruction or agents for biologic terrorism. Agents such as smallpox, viral hemorrhagic fever viruses, agents of viral encephalitis, and others are of concern because they are highly infectious and relatively easy to produce. Although dispersion might be difficult, the risk is magnified by the fact that large populations are susceptible to these agents and only limited treatment and vaccination strategies exist. Although the risk of large-scale bioterrorism using viral agents is small, public health programs and health care providers must be prepared for this potentially devastating impact on public health.