Toxins as weapons of mass destruction. A comparison and contrast with biological-warfare and chemical-warfare agents.

Toxins are toxic chemical compounds synthesized in nature by living organisms. Classifiable by molecular weight, source, preferred targets in the body, and mechanism of action, they include the most potent poisons on the planet, although considerations of production, weaponization, delivery, environmental stability, and host factors place practical limits on their use as WMD. The two most important toxin threats on the battlefield or in bioterrorism are probably botulinum toxin (a series of seven serotypes, of which botulinum toxin A is the most toxic for humans) and SEB, an incapacitating toxin. Ricin and the trichothecene mycotoxins, including T-2 mycotoxin, are of lesser concern but are still potential threats. Botulinum toxin is a neurotoxin, ricin and trichothecene mycotoxins are membrane-damaging proteins, and SEB is a superantigen capable of massive nonspecific activation of the immune system. The clinical intoxications resulting from exposure to and absorption (usually by inhalation) of these agents reflect their underlying pathophysiology. Because of the hybrid nature of toxins, they have sometimes been considered CW agents and sometimes BW agents. The current trend seems to be to emphasize their similarities to living organisms and their differences from CW agents, but examination of all three groups relative to a number of factors reveals both similarities and differences between toxins and each of the other two categories of non-nuclear unconventional WMD. The perspective that groups toxins with BW agents is logical and very useful for research and development and for administrative and treaty applications, but for medical education and casualty assessment, there are real advantages in clinician use of assessment techniques that emphasize the physicochemical behavior of these nonliving, nonreplicating, intransmissible chemical poisons.

A field-expedient algorithmic approach to the clinical management of chemical and biological casualties.

Warriors on the modern battlefield face considerable danger from possible attack with chemical and biological weapons. Aggravating this danger is the fact that medical resources at the lowest echelons of care, already likely to be strained to capacity during modern conventional combat, are at present inadequate to handle large numbers of chemical or biological casualties. Complicating this problem further is the austere nature of diagnostic modalities available at lower echelons. With this in mind, and given the urgency required to adequately manage chemical and biological casualties, it is likely that such casualties will initially require significant empiric care in the absence of a definitive diagnosis. Such care under field conditions, often rendered by relatively inexperienced medical personnel, might best be provided using an algorithmic approach. We have developed such an algorithm.

Hypothesis for synergistic toxicity of organophosphorus poisoning-induced cholinergic crisis and anaphylactoid reactions.

The neurotoxicity of organophosphorus (OP) compounds involves the inhibition of acetylcholinesterase (AChE), causing accumulation of acetylcholine (ACh) at synapses. However, cholinergic crisis may not be the sole mechanism of OP toxicity. Adverse drug reactions caused by synergistic toxicity between drugs with distinct pharmacological mechanisms are a common problem. Likewise, the multiple pharmacological activities of a single molecule might also contribute to either toxicity or efficacy. For example, certain OP compounds (e.g. soman) exhibit anti-AChE activity and also act as secretagogues by inducing mast cell degranulation with associated autacoid release and anaphylactoid reactions. Anaphylactoid shock can produce a lethal syndrome with symptoms of respiratory failure and circulatory collapse similar to the physiological sequelae observed for OP poisoning. Moreover, the major classes of drugs used as antidotes for OP intoxication can affect anaphylaxis. Acetylcholine can act as an agonist of autacoid release, and autacoids such as histamine can augment soman-induced bronchial spasm. In concert with the demonstrably critical role of cholinergic crisis in OP toxicity, the precepts of neuroimmunology indicate that secondary adverse reactions encompassing anaphylactoid reactions may complicate OP toxicity.

The role of immunoglobulin binding factors in the pathogenesis and therapy of AIDS.

The human immunodeficiency virus (HIV) gp120 and gp41 envelope proteins and Staphylococcus aureus protein A (SPA) all have Fc receptor (FcR)-like immunoglobulin binding factor (IBF) activity for the Fc constant fragments of human immunoglobulin G (IgG). Viral IBF may contribute to the pathology of HIV by jamming the network of FcR signals that control FcR-dependent immunity. Conversely, the bacterial IBF SPA has anti-retroviral activity that may involve antagonism of the immunopathological action of viral IBF, strongly suggesting IBF may act as a double-edged sword that might be turned against viral invaders.