Elizabeth Randall

A Modification of the Technic for Determination of the Antistreptolysin Titer.

Summary 1. A modified technic for the determination of the antistreptolysin titer of serum has been described which involves the use of a concentrated lysin reduced to the active form at the time of use.

THE ABSORPTION AND EXCRETION OF PENICILLIN FOLLOWING CONTINUOUS INTRAVENOUS AND SUBCUTANEOUS ADMINISTRATION

Penicillin, a product of the growth of a fungus, penicillium notatum, has become established as a therapeutic agent of value in the management of various infections, particularly those caused by the pyogenic cocci (1). Because penicillin is unstable in the presence of acid, it may not be given by mouth and absorption from the duodenum is imperfect. It has, therefore, been administered parenterally in nearly all of the recorded clinical studies. Three routes have usually been used: (1) intermittent intravenous; (2) intermittent intramuscular; and (3) continuous intravenous. Adequate clinical results have been obtained with each but in only one instance have studies been made of the fate of the injected material. It has been shown (2) that the injection of a single large dose of penicillin, intravenously, was followed by a very rapid rise and fall of the blood level of this substance, so that at the end of 2 hours, the amount remaining was not detectible by the method used. During this interval, about 60 per cent of the injected penicillin appeared in the urine. Absorption was somewhat slower and the blood levels were lower but better maintained following intramuscular administration. Absorption from the subcutaneous tissues was irregular, and the levels reached in the blood were low. The use of the continuous intravenous drip for the administration of penicillin has been advocated (3). This author has suggested a daily dose of 50,000 units, but has not studied the concentrations of the drug in the blood or urine. It is the purpose of this report to describe the results of determinations of blood and urine concentrations of penicillin obtained during the study of patients under treatment with this agent, all of whom received penicillin by continuous intravenous or subcutaneous drip. METHODSAND MATERIALS

Immunization of human beings with group A hemolytic streptococci

Abstract 1.1. Heat-killed group a hemolytic streptococci were administered subcutaneously to human beings. 2.2. Type specific and other antibacterial antibodies developed only in those subjects who received a very large amount of vaccine over a nine-week period. 3.3. Toxic reactions were severe following the injection of small amounts of vaccine in certain persons. Others accepted much larger amounts without difficulty. 4.4. Increased reactivity to the injection of hemolytic streptococci developed in some subjects. This is believed to represent artificially induced sensitivity of an immunologic type to the streptococcus or its products. The authors are grateful to Warden Clinton Duffy, Dr. Leo Stanley and those prisoners of San Quentin prison whose voluntary cooperation made this work possible.

Renal tubular excretory capacity for penicillin in health and in subacute bacterial endocarditis

I T has been amply shown that penicillin is largely excreted by the kidneys without appreciable destruction in the body’ and that this process occurs rapidly’ thus playing an important part in limiting the usefulness of that drug in the treatment of infection. The belief that penicillin leaves the kidneys not only through glomerular filtration but also by tubular excretion has been substantiated by the work of Rantz and Kirby2 on penicillin clearances. These investigators showed that the amount of blood cleared of penicillin by the kidneys per minute compared with that cleared of diodrast, another substance excreted by the renal tubules.3 In addition the clearance values of penicillin are far higher than those of such drugs as inulin which is known to be excreted solely by glomerular filtration. Rammelkamp and Bradley,4 who showed that elimination of penicillin is retarded when penicillin and diodrast are given simultaneously, suggested that there existed between these two drugs a competition for the same mechanism of tubular excretion. This has also been shown to be true of paraaminohippuric acid. 5 It was of practical importance, therefore, to know the maximal tubular excretory capacity (TM,) of the kidneys for penicillin since doses of the drug surpassing TM, would be expected to produce relatively more rapid rises in the blood levels of penicillin than amounts under this level. It is already known that with renal damage penicillin excretion is hindered along with other renal functions and that high and sustained blood levels may follow relatively small doses. 6 In diseases in which renal damage occurs and which are susceptible to treatment with penicillin renal failure might then paradoxically exert a favorable influence on the direct outcome of the illness. One disease to which these events are applicable is subacute bacterial endocaiditis which in most cases has been found highly amenable to penicillin and in which a high percentage of cases has more or less renal damage.’ It is of interest then to know of how much importance the renal damage in subacute bacterial endocarditis is in producing higher than usual blood levels of penicillin. Loewe, Rosenblatt and Alture-Werber8 found that in a case of a patient with resistant endocarditis receiving large doses of penicillin by continuous intravenous drip the serum levels of penicillin began to rise above the expected levels when a dose of 625,000 units per hour was reached. It was suggested that at this. dosage the TM of penicillin had been attained. It has been shown that with lower continuous intravenous dosages the rise in serum penicillin concentration is directly proportional to the increase in dose.2 With these points in mind, serum levels, urinary excretion and serum clearances of penicillin in normal individuals and in patients with subacute bacterial endocarditis have been studied. * From the Department of Medicine, Stanford University School of Medicine, San Francisco, Calif.

Stable, Reduced, Desiccated Streptolysin " O ".

Discussion and Summary A method is described for the preparation of a very stable, desiccated, reduced streptolysin “O”. The material, when reconstituted with distilled water, is suitable for use in the determination of the antistreptolysin “O” titer of human serum. The availability of this material greatly simplifies this procedure since it is always immediately ready for use without the addition of the reducing agent. In addition, it may be shipped and stored conveniently since refrigeration is not required. Its production on a large scale or commercial basis would not prove difficult if a sufficient need for this material should arise.

Sulfonamide and penicillin resistance of group A hemolytic streptococci.

Summary Strains of certain types of Group A hemolytic streptococci were discovered to be naturally resistant to moderate amounts of sulfadiazine. It is suggested that such organisms originated the epidemics of streptococcal disease among troops receiving sulfonamide prophylaxis, later becoming more resistant by mutation. No strains significantly resistant to penicillin were discovered.