Recombinant alpha 1-antitrypsin Pittsburgh attenuates experimental gram-negative septicemia.

Alpha 1-antitrypsin-Pittsburgh (AT-P), a naturally occurring lethal mutation (358Met----Arg), has been genetically engineered (rAT-P). The protein has been shown to be a potent active site-directed inhibitor of thrombin and the contact enzymes Factor XIIf, Factor XIa, and kallikrein. Because activation of the contact system is known to occur in gram-negative septicemia, the authors have hypothesized that the administration of rAT-P might modulate the course of this syndrome. Yorkshire piglets anesthetized with pentobarbital and infused with viable Pseudomonas aeruginosa (2 X 10(8) CFU) were untreated (Group I) or treated with rAT-P (Group II) and studied in a 6-hour protocol. Coagulation studies revealed that rAT-P significantly inhibited the rapid decrease in the functional concentrations of Antithrombin III, Factor XI, and fibrinogen. In addition, rAT-P markedly reduced the serum levels of fibrinogen degradation products. Survival in Group II was significantly increased during 2-5 hours but not at 6 hours when the functional levels of rAT-P in plasma were the lowest. These results indicate that this recombinant inhibitor, even at low concentrations, affords protection in experimental gram-negative septicemia.

Oral vs repository corticosteroid therapy in acute asthma.

Acutely ill asthmatic patients treated in the usual fashion in an emergency room setting and discharged within six hours were studied to determine whether therapy with a single injection of a repository corticosteroid (methylprednisolone sodium acetate) could be as effective as a tapering course of oral corticosteroids in decreasing asthma symptomatology and relapse within seven days. Seventeen patients (18 episodes of asthma) formed the study population. Eight episodes occurred in patients who received depot methylprednisolone (group 1) and ten episodes in patients who received oral corticosteroid treatment (group 2). All patients in both groups improved following emergency room treatment. Relapse occurred in two of ten patients in group 2 and none in group 1. Symptoms attributable to asthma recurred in significantly more patients in group 2 than in group 1 (9 vs 0, p less than .01). Side effects from therapy with corticosteroids were rare. This study indicates that intramuscular repository corticosteroids are at least as effective as oral corticosteroids in the management of the acute asthmatic outpatient, with a distinct advantage with regard to patient compliance.