Wesley W. Spink

Canine Intestinal and Liver Weight Changes Induced by E. colt Endotoxin

Summary 1. Systemic arterial blood pressure response of the dog to injection of Es-cherichia coli endotoxin is characterized by a sudden precipitous drop, a partial recovery and a subsequent slower decline over a period of hours. 2. Utilizing a device for quantitatively estimating changes in weight of organs in vivo, an increase in liver weight of from 80 to 350 g has been noted within one to 2 minutes following injection of E. coli endotoxin. 3. Simultaneous increase in weight of small intestine of lesser magnitude (28 to 170 g) was noted at the same time and is believed to be due to back pressure from the liver. Increase in liver and intestinal weight were believed to be quantitatively sufficient to account for the hypotension observed. 4. A difference in reaction of the liver and intestine was noted. Whereas the liver returns to normal weight within 5 to 25 minutes, the small intestine continues to increase in weight reaching a maximum of from 196 to 770 g approximately one hour following endotoxin injection. 5. The secondary hypotension due to endotoxin is believed to be at least partially the result of loss of blood in the small intestine due to vascular damage in this organ.

Evaluation of Plasma, Metaraminol, and Hydrocortisone in Experimental Endotoxin Shock

An experimental model of canine endotoxin shock was employed for evaluating therapeutic agents that are used in the management of peripheral vascular collapse. An important feature of the present study was that an agent or agents were not administered until hypotension and oligulria were present. Progressive endotoxin shock was not reversed by the infusion of large amounts of canine plasma. Large doses of hydrocortisone did not prevent a lethal outcome. Even though the blood pressure was stabilized near normotensive levels with the vasopressor drug, metaraminol, progressive shock occurred. The most significant finding was that lethal endotoxin shock was prevented in six of the 10 animals studied by the simultaneous use of hydrocortisone and metaraminol. Only one-eighth the amount of metaraminol was necessary to maintain normotensive levels of blood pressure if a large dose of hydrocortisone was administered before the infusion of the pressor drug.

In vitro Sensitivity of Brucella to Streptomycin : Development of Resistance during Streptomycin Treatment.

Summary 1. A method for the in vitro testing of sensitivity of brucella to streptomycin is described. 2. The streptomycin sensitivity of 40 cultures of brucella isolated from humans is given. 3. Studies are reported concerning a strain by Br. abortus which developed marked resistance to streptomycin during the treatment of a patient having subacute bacterial endocarditis.

Comparative in vitro Resistance of Staphylococci to Penicillin and to Sodium Sulfathiazole

Discussion and Conclusions When 68 strains of pathogenic staphylococcus were subjected to the in vitro action of sodium penicillin, 8 of the strains, or approximately 12%, were found to be quite resistant, requiring from 0.4 units per cc to 0.8 units of penicillin before growth was completely inhibited. The growth of the remaining 60 strains necessitated the following amounts of penicillin before growth was inhibited: 22 strains, or about 3276, required 0.2 units; 25 or approximately 3776, required 0.1 unit; while 12 or about 1870, failed to grow in the presence of 0.05 unit. About 28% of the strains were found to be highly resistant to the antistaphylococcic action of sodium sulfathiazole. There was no relationship between resistance to penicillin and to the sulfonamide. The evidence at hand would indicate that the mechanism whereby staphylococci become resistant to the sulfonamides is different and unrelated to the development of resistance to penicillin. 10-14 Since some strains of staphylococcus isolated from patients appear to be naturally resistant to penicillin, and yet, sensitive to sodium sulfathiazole, it would not be unreasonable to assume that a combination of therapy with penicillin and sulfathiazole might be advantageous in the management of some types of staphylococcic sepsis. Further clinical observations are necessary to substantiate this, but preliminary investigations appear to bear out this assumption.

THE CLINICAL PROBLEM OF ANTIMICROBIAL RESISTANT STAPHYLOCOCCI

A publication devoted to Microiocczis pyogerces and the responses of the invaded host is timely because of the serious problem that antibiotic-resistant staphylococci poses for the clinician. No attempt will be made to review the extensive literature on the subject, since such a summary has been made elsewhere. This report will be concerned primarily with the problem of staphylococcal sepsis as it has been encountered a t the University of Minnesota Hospitals and its affiliated clinics since 1937, thus permitting the development of the over-all picture of staphylococcal infections as it has been seen in one medical center.

Endotoxin Shock and the Coagulation Mechanism Modification of Shock with Epsilon-Aminocaproic Acid

Summary 1. Lethal shock was established with a standardized dose of E. coli endotoxin in adult mongrel dogs. In this species initiation of the peripheral vascular collapse involves liberation of histamine, which may be related to the activation of a proteolytic system by the endotoxin. 2. Pre-treatment of dogs with epsilon-aminocaproic acid (EACA), a potent inhibitor of plasminogen activator, protected the majority of animals against a lethal dose of endotoxin. Protection was also observed when EACA was given up to 30 minutes after injection of endotoxin. However, when EACA was administered beyond this time no protection occurred, and there was no evidence that the severity of the shock was modified. It is emphasized that these observations with EACA apply only to the dog. 3. The primary purpose of the present experiments was to determine if EACA protected dogs against lethal amounts of endotoxin. The results do not permit the conclusion that EACA modified the severity of shock by blocking plasminogen activation, and in this manner prevented liberation of histamine. There remains the possibility EACA blocked proteolytic activity that is independent of the plasminogen-plasmin system.

Comparative Action of Aureomycin, Chloromycetin, Neomycin, Q-19, and Polymyxin B Against Gram Negative Bacilli

Summary and Cnclusions Twenty strains each of E. Coli, Aerobacter aerogenes, Pseudomonas, and Proteus vulgaris were tested for sensitivity to neomycin, Q-19, aureomycin, chloromycetin, and Polycyxin B. Q-19 and polymyxin B were particularly effective against Pseudomonas. Neomycin and chloromycetin were most effective against Proteus. Only 5 of the 80 strains tested were not sensitive to 31.2 μg or less of neomycin. The degree of resistance possessed by variants exposed to Q-19 and neomycin is low. These variants display the “penicillin” rather than the “streptomycin” type of drug resistance. Q-19 and neomycin are bactericidal in a concentration equal to or only slightly higher than that in which they are bacteriostatic.

Antibacterial Effect of Whole Blood upon Strains of Staphylococci Sensitive and Resistant to Penicillin

Discussion and Conclusions Strains of staphylococcus adapted to grow in the presence of the sulfonamides are just as invasive as other strains which are inhibited in growth by the sulfonamides. Whole, human blood has no greater bactericidal action on the sulfonamide-resistant strains than on the sulfonamide-sensitive strains. Strains of staphylococcus adapt themselves to grow in the presence of penicillin at a slower rate and to a lesser degree than is apparent for the sulfonamides. And probably of considerable clinical importance is that an increas d resistance to penicillin is accompanied by the development of strains which are more susceptible to the bactericidal action of whole blbod, and possibly to the other defense mecbanisms of the host.

Hemodynamic Effects of Vasopressor Agent (Metaraminol)∗ on Hypotension in Dogs Produced by Endotoxin

Conclusions and summary The early shock produced in the dog by the injection of Gram-negative endotoxin is the result of venous pooling and greatly diminished venous return. Intravenous administration of metar-aminol (Aramine) prevented further pooling. Venous return was effectively increased and the mechanism through which the shock was initiated was therefore counteracted.

Penicillin Inhibitor from Staphylococci Which Have Developed Resistance to Penicillin in the Human Body

Summary Strains of staphylococci which have developed resistance to penicillin in the human body yield an inhibitor for penicillin. Penicillin inhibitor was not present in 4 strains which had been made highly resistant by exposure in vitro. Resistance developed in vivo was found, among the strains tested, to be a more permanent characteristic of staphylococci than that acquired in vitro.