Showing papers by "N. Franklin Adkinson published in 1985"

Inflammatory Mediators in Late Antigen-Induced Rhinitis

Abstract: To investigate the mechanisms responsible for the late-phase response in patients with allergies, we measured four biochemical mediators (histamine, tosyl-L-arginine methyl ester [TAME]—esterase, kinin, and prostaglandin D2) in nasal secretions after nasal challenge with pollen antigen in 12 patients with allergy. Nine patients had an immediate response and a recurrence of symptoms 3 to 11 hours after challenge. The clinical symptoms during recurrence were accompanied by a second increase in levels of histamine, TAME—esterase, and kinin over base-line values, although kinin levels were lower than during the immediate response. In contrast, although the levels of prostaglandin D2 were significantly increased during the immediate response, they did not increase above base line during the late response. Rechallenge with allergen 11 hours after the initial provocation, however, was associated with reappearance of all four biochemical mediators, including prostaglandin D2. We conclude that the late re...

Cross-Allergenicity and Immunogenicity of Aztreonam

Abstract: The immunochemistry of aztreonam, the prototype of the new monobactam class of beta-lactam antibiotics, was studied in a series of experimental and clinical investigations. Rabbit antibodies to aztreonam and naturally occurring human antibodies that recognize aztreonam were found to have negligible cross-reactivity with benzylpenicillin, cephalothin, and cefotaxime. Aztreonam likewise displayed negligible cross-reactivity (less than or equal to 0.001%) with antibodies to penicillin (including human IgE antibodies to major and minor penicillin determinants) and to cephalothin. These studies suggest that aztreonam may be well tolerated by penicillin-allergic individuals, and this possibly is now being evaluated in clinical trials. Seven (6.25%) of 112 healthy persons tested had preexisting IgG antibodies to aztreonam in low titer, presumably as a result of exposure to naturally occurring cross-reacting moieties. Only two of seven patients with preexisting IgG antibodies to aztreonam had a rise in titer following aztreonam treatment. No IgE antibody to aztreonam was detected in serum specimens obtained on day 10 during any of the 112 courses of therapy. These clinical observations suggest but do not prove that aztreonam has only weak potential to elicit a drug-specific immunologic response.

Inhalation anesthetics augment oxidant-induced pulmonary vasoconstriction: evidence for a membrane effect.

Abstract: Inhalational anesthetics "fluidize" biologic membranes. Since arachidonate metabolism also occurs in cell membranes, anesthetic agents may modify arachidonic acid mediator production. The authors used the isolated perfused rabbit lung preparation to examine the effects of inhalational anesthetics on the production of arachidonate mediators. The oxidant tert-butyl-hydroperoxide (t-bu-OOH) is known to cause pulmonary vasoconstriction by causing increased production of thromboxane A2 (TxA2). The authors administered three anesthetics (halothane, cyclopropane, and nitrous oxide) of widely different potencies, at different dosages, each to three different groups of preparations and challenged the lungs at each anesthetic dose with t-bu-OOH. They found a dose-related augmentation of the pulmonary vasopressor response to t-bu-OOH. Preparations given t-bu-OOH alone showed no change in response over time. Lungs perfused with indomethacin (5 micrograms . ml-1 in Krebs-Henseleit buffer), ventilated with cyclopropane (2 MAC), and challenged with t-bu-OOH showed almost complete inhibition of the response to t-bu-OOH. Indomethacin at this concentration is a specific inhibitor of cyclooxygenase. The authors also have demonstrated significantly increased perfusate levels of thromboxane B2 (TxB2), the inactive metabolite of TxA2, after oxidant challenge during exposure to 2% halothane compared with TxB2 levels before halothane exposure. The authors believe that the augmented pressor response and mediator production occur because of increased substrate (arachidonic acid) availability induced by anesthetic agent.