Summarv polymyxin B has antiendotoxin activity which is distinct from itsThe antiendotoxin effect of polymyxin B was investigated in experimentally induced septicemia in rabbits. The Pasteurella multocida organisms were sensitive to the antibacterial action of penicillin but not to polymyxin B. Animals pre-treated with polymyxin showed positive blood cultures and significantly reduced plasma endotoxin levels (Limulus test) with normal white blood cell and platelet counts when analyzed 6 hr after the injection of live organisms. Polymyxin therapy given after the animals had LntibLterial power. Heretofore, all ofthe studies that have been reported have employed either the purified lipopolysaccharide or dead gram-negative organisms. The purpose of this study was to investigate the effect of polymyxin B on endotoxin activity in a rabbit model of gram-negative septicemia. The endotoxin effects investigated were the changes in plasma endotoxin activity, and the white blood cell and platelet counts in animals who were treated with polymyxin B sulfate.established septicemia-endotoxemia reduced the plasma endotoxin levels and improved the survival, but had no effect on the leuko-MATERIALS AND METHODS penia and thrombocytopenia. The best survival data were obtained White rabbits of both sexes, California strain, weighing 1.0 kg in rabbits who were treated with both penicillin and polymyxin. were used. They were housed in an air-conditioned isolated animal The data suggest that polymyxin is effective in neutralizing the room and fed antimicrobial free rabbit chow and water ad libitum. endotoxic effects from live organisms and that the timing and The production of gram-negative septicemia in these rabbits was perhaps duration of the polymyxin treatment is of critical impor-by methods previously described (4). In essence, the animals were tance. In addition, a modified Limulus lysate method was devel-given 2 x 10"ive P. multocida organisms per kg body wt ip. The oped which showed that quantitative plasma endotoxin determi-animals regularly became clinically ill and had positive blood nation could be made more sensitive by prior heating of the plasma cultures and Limulus lysate tests 4-6 hr after the injection. Seto remove the natural inhibitors.quential blood samples were obtained from the heart and were used for blood cultures, endotoxin assay and leukocyte and platelet Speculation counts. Quantitative colony counts using heparinized whole blood were performed by pour plate technique on 5% blood agar plates his investigation and other reports have shown that ~o l~m~x i n (h4icro-~ech Diagnostics, Tucson, AZ). The plates were incubated B sulfate neutralized endotoxin effects in animals given purified at 370 and 24 hr later the small, mucoid gray, nonhemolytic endotoxin, dead endotoxin-containing organisms, and gram-nega-colonies were counted, tive septicemic animals (3,6,8,(12)(13)(14)(15). The antiendotoxin effect ~~~~~i~i~~d plasma was obtained by ofthe blood of the antibiotic appears to be separate from its antimicrobial ...

Young rabbits were given live encapsulated or heat-hilled Pasteurella multocida by the intraperitoneal route. Those animals given live organisms regularly developed clinical illness, positive blood cultures, positive limulus lysate tests on plasma, leukopenia, thrombocytopenia, and disseminated intravascular coagulation and died. Death occurred in 68% of these rabbits by 12 hr after infection and in 100% by 24 hr. Septicemic animals given heparin as an anticoagulant similarly developed clinical illness, leukopenia, and thrombocytopenia, but no laboratory evidence of disseminated intravascular coagulation. The mortality rate in these animals was 90% 12 hr after infection and 100% 24 hr after infection. None of the animals given heat-killed organisms developed leukopenia, thormbocytopenia, or disseminated intravascular coagulation, and none died. The data show that the survivial rate in septicemic rabbits was not improved with heparin, although fibrinogen consumption (disseminated intravascular coagulation) was abolished.

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Epsilon aminocaproic acid, an inhibitor of plasminogen and trypsinogen activators, can decrease the severity of experimental allergic encephalomyelitis (EAE) in rats. The drug was tried because of a number of observations suggesting that neutral proteases, such as plasmin, might be chemical mediators of demyelination. The highest concentrations of plasminogen activator are found in the walls of veins and venules, around which demyelination is common in many demyelinating diseases, including MS. Indeed, the earliest lesion in MS is often demyelination with little cellular infiltration. In vitro studies have shown that neutral proteases secreted by activated macrophages selectively lyse myelin basic protein.

Department of P e d i a t r i c s , Cleveland. Ohio. Several recent s t u d i e s i n a d u l t s have indicated t h a t CIE a s opposed t o r o u t i n e c u l t u r e of sputum can d i s t i n g u i s h p a t i e n t s with pneumococcal pneumonia vs. those simply colonized with t h e