Ralph R. Mellon

Action of P-Aminobenzenesulfonamide on Type III Pneumococcus Infections in Mice

Conclusions The oral administration of p-aminobenzenesulfonamide is capable of prolonging, and in some cases of saving, the lives of mice infected subcutaneously with approximately 10 minimal lethal doses of highly virulent Type 111 pneuniococci.†, ‡

Anticatalase Activity of Sulfanilamide and Related Compounds. III. Oxygen Tension and Bacteriostasis in Pneumococcal Cultures

Summary 1. Reduction of the percentage of oxygen in the superambient air of broth cultures of the Type I pneumococcus greatly reduced or prevented bacteriostasis by sulfanilamide. 2. When the oxygen concentration was reduced to 0.04% an actual stimulus of growth by sulfanilamide was found. 3. When the oxygen was further reduced by the presence of pyrogallate or hydrosulfite the inhibition by sulfanilamide reappeared. 4. Hydrogen peroxide was detected only in cultures in equilibrium with atmospheres containing 10% oxygen or more. These concentrations correspond to those permitting effective bacteriostasis and are comparable to those obtainable in the plasma. 5. The lack of inhibition at intermediate concentrations shows that oxygen plays a vital rôle in the action of sulfanilamide. The failure to form peroxide at these same concentrations is taken as evidence that oxygen exerts its influence through the agency of hydrogen peroxide. The stimulus and recurring inhibition at the lowest values is interpreted as evidence of the formation of a toxic reduction compound, possibly a sulfide. The latter type of inhibibition may play a rôle in any bacteriostatic effect against anaerobes.

Therapy of Experimental Staphylococcus Infections with Sulfonamide Compounds

Conclusions Generally speaking, our experience with these drugs in staphylococcic infections is in marked contrast to the decisively favorable results of sulfanilamide in hemolytic streptococcal infections. Disulfanilamide, by virtue of its apparent therapeutic effect over a limited time period has a certain promise, which, however, failed of clinical confirmation in the small number of cases observed. A more diversified experimental trial is merited. Both experimentally and clinically the results with “Di-Septal” in this preliminary study were essentially negative.

Anticatalase Activity of Sulfanilamide and Related Compounds. I. Effect of Ultraviolet Irradiation

Conclusions The ability of sulfanilamide and structurally related compounds to develop color on ultraviolet irradiation appears to be dependent on the presence or absence of substituents in the p-amino and sulfamido groups. A study of the anticatalase properties of sulfanilamide and related compounds indicates a possible correlation between therapeutic activity and the intrinsic anticatalase activity associated with the non-irradiated compound. Neither color production nor the high anticatalase activity developed as a consequence of irradiation appear to be related to therapeutic effectiveness.

Nuclear Phenomena Suggesting a Sexual Mechanism for the Tubercle Bacillus

Summary Stained preparations of a non-acid-fast phase of the tubercle bacillus show nuclear structures resembling chromosomes, and nuclear changes suggesting a sexual mechanism.

Anti-Catalase Activity of Sulfanilamide and Related Compounds. VI. Further Studies on Sulfonhydroxamides

Summary P-Caproylaminobenzenesulfonhydroxamide produces bacteriostasis of pneumococci in blood without the lag characteristic of sulfanilamide. The activity is only about one-eighth of the corresponding bacteriostatic power in broth. That the immediate nature of the effect is due to the hydroxamide group was demonstrated by the use of p-toluenesulfonhydroxamide in which the potentially active p-amino group is absent. The effect of the hydroxamide group is transient in nature. A second period of bacteriostatic activity manifested by p-caproylaminobenzenesulfonhydrox-amide is probably due to the free amino group formed by deacylation of the caproylamino group.

Anticatalase Activity of Sulfanilamide and Related Compounds. V. Bacteriostatic Activity of some Sulfonhydroxamides

Summary The acyl aminobenzenesulfonhydroxamides have strong anti-catalase activity and, when present in broth cultures of the pneumococcus, cause inhibition of growth associated with increased accumulation of hydrogen peroxide. When the caproyl compound is added to growing cultures, inhibition of growth is detectable almost immediately but reaches a maximum only after time for accumulation of peroxide has elapsed. Inhibition by sulfanilamide, on the other hand, is detectable somewhat later and approaches a maximum more slowly.

Anticatalase Activity of Sulfanilamide and Related Compounds. IV. Peroxide Accumulation and Growth Inhibition in Pneumococcus

Summary The effect of sulfanilamide, and other compounds capable of inhibiting catalase, upon growth and accumulation of hydrogen peroxide in broth cultures of the pneumococcus has been subjected to quantitative measurement. The concentration of peroxide per unit of growth was from 2 to 10 times greater in the presence of compounds which caused bacteriostasis than in control cultures.

A New Approach to the Therapeusis of Hemolytic Streptococcal Infections

Conclusion 1. In a series of 118 cases of general hemolytic strep tococcal infectims a mortality of but 12% has attended the administration of antisera prepared from 2 anomalous dissociants of a cellulitic strain of hemolytic streptococcus. 2. The objective of the treatment has been the ipt. Gvo transformation of the virulent types to dissociants whose virulence is diminished or absent. Clinical bacteriological evidence of this effect is submitted. 3. Associated with recovery of the patient is a return of the calcium-phosphorus product of the blood to normal. This product is usually lowered during the active stages of the disease.

Experiments on the Filtrability of the Rosenow Streptococcus of Anterior Poliomyelitis

This paper deals with the successful filtration through Berkefeld candles of 2 strains of the Rosenow anterior poliomyelitis streptococcus. These strains were designated 1630.30 and 1694 1 .50. 0.5 cc. of a 20-hour brain infusion broth culture of 1630.30 was inoculated intracerebrally into each of 3 rabbits. Two of these animals died in less than 24 hours, and the third in 36 hours. Autopsies showed typical cerebral meningitis. From cultures of the brain, meninges, and cerebral exudate, the original streptococcus was recovered in each case. Heart blood cultures were negative. The brains of these 3 animals were emulsified in broth and 0.5 cc. reinoculated intracerebrally into fresh rabbits. Death again resulted in approximately 18 hours, with recovery of the streptococcus. Animals inoculated with 0.5 cc. of the Berkefeld N filtrate of these emulsions suffered no ill effects. By intensive cultivation of these 3 brain emulsion filtrates using the Hauduroy transplant method on blood agar plates, we were able to recover from 2 of them an organism resembling both microscopically and culturally the 1630.30 streptococcus. In all cases it appeared on the 4th to 6th plate in the series. Identically this same procedure was carried out using the 1694 1 .50 strain Three rabbits were inoculated intracerebrally. All showed meningitis symptoms but only one died (48 hours). The streptococcus was recovered from brain cultures of this animal, but not from the heart blood. An organism believed to be 1694 1 .50 was also recovered from the brain filtrate in the same way as for the 1630.30 strain. Then each of the 4 strains was treated in the following manner: 20 cc. of a 24-hour hrain heart infusion hroth culture was injected intraperitoneally into a small half-gronn rahlit and 50 cc. into a large rabbit.