Raymond Kaempfer, PhD, Gila Arad, PhD, Revital Levy, BA and Dalia Hillman, BA
Background: Superantigens produced by Staphylococcus aureus and Streptococcus pyogenes are among the most lethal of toxins. Toxins in this family trigger an excessive cellular immune response leading to toxic shock.
Objectives: To design an antagonist that is effective in vivo against a broad spectrum of superantigen toxins.
Methods: Short peptide antagonists were selected for their ability to inhibit superantigen-induced expression of human genes for cytokines that mediate shock. The ability of these peptides to protect mice against lethal toxin challenge was examined.
Results: Antagonist peptide protected mice against lethal challenge with staphylococcal enterotoxin B and toxic shock syndrome toxin-1, superantigens that share only 6% overall amino acid homology. Moreover, it rescued mice undergoing toxic shock. Antagonist peptides show homology to a β-strand/hinge/a-helix domain that is structurally conserved among superantigens, yet remote from known binding sites for the major histocompatibility class II molecule and T cell receptor that function in toxic T cell hyperactivation.
Conclusions: The lethal effect of superantigens can be blocked with a peptide antagonist that inhibits their action at the top of the toxicity cascade, before activation of T cells occurs. Superantigenic toxin antagonists may serve not only as countermeasures to biologic warfare but may be useful in the treatment of staphylococcal and streptococcal toxic shock, as well as in some cases of septic shock.
Jacob T. Cohen, MD, Gil Ziv, MD, PhD, Joseph Bloom, MD, Daniel Zikk, MD, Yoram Rapoport, MD and Mordechai Z. Himmelfarb, MD
Background: The ear is the most frequent organ affected during an explosion. Recognition of possible damage to its auditory and vestibular components, and particularly the recovery time of the incurred damage, may help in planning the optimal treatment strategies for the otologic manifestations of blast injury and preventing deleterious consequences.
Objective: To report the results of the oto-vestibular initial evaluation and follow-up of 17 survivors of a suicidal terrorist attack on a municipal bus.
Methods: These 17 patients underwent periodic ear inspections and pure tone audiometry for 6 months. Balance studies, consisting of electronystagmography (ENG) and computerized dynamic posturography (CDP) were performed at the first time possible.
Results: Complaints of earache, aural fullness and tinnitus resolved, whereas dizziness persisted in most of the patients. By the end of the follow-up, 15 (55.6%) of the eardrum perforations had healed spontaneously. Hearing impairment was detected in 33 of the 34 tested ears. Recovery of hearing was complete in 6 ears and partial in another 11. ENG and CDP were performed in 13 patients: 5 had abnormal results on CDP while the ENG was normal in all the patients. The vertigo in seven patients resolved in only one patient who was free of symptoms 1 month after the explosion.
Conclusion: Exposure to a high powered explosion in a confined space may result in severe auditory and vestibular damage. Awareness of these possible ear injuries may prevent many of the deleterious consequences of such injuries.