1
Western Society for Clinical Research The incidence of significant circulating anti- toxin one month after two injections in twenty- one patients and the incidence of Schick nega- tivity three months after three injections in all patients will be reported. ANTIBIOTIC ANTAGONISM: THE INTERFERENCE OF CHLORAMPHENICOL, AUREOMYCIN AND TER- RAMYCIN WITH THE ACTION OF PENICILLIN IN EXPERIMENTAL INFECTIONS AND IN VITRO. E. Jawete, * J. B. Gunnison and R. S. Speck, Division of Bacteriology, University of Cali- fornia, School of Medicine, San Francisco, Calif. Antagonistic effects between the three “newer” antibiotics and penicillin have been demon- strated in oitro and in experimental infections of mice with both gram positive (hemolytic strep- tococcus) and gram negative (Klebsiella pneu- moniae) organisms. The antagonism between penicillin and either chloramphenicol, aureo- mycin or terramycin extends over considerable ranges of concentrations of each drug, including concentrations commonly achieved in human body fluids with therapeutic doses. The phe- nomenon is limited by the degree of anti- microbial activity of each drug: Concentrations below the bacteriostatic level for a given micro- organism as well as concentrations possessing marked bactericidal activity are without inter- fering effect. Antibiotic antagonism is observed in experi- mental infections when the drugs are given at the same or different sites, in single or multiple doses. However, antagonism occurs only if chloramphenicol, aureomycin or terramycin are administered simultaneously with or prior to penicillin, not if penicillin is given first. Certain drugs which are synergistic with penicillin, e.g., streptomycin or bacitracin, can overcome anti- biotic antagonism. The experimental evidence indicates that the phenomenon is not one of mutual antagonism between the drugs concerned but rather an interference of chloramphenicol, aureomycin or terramycin with the early bactericidal and therapeutic effects of penicillin. The antagonistic drugs do not appear to interact physically or chemically so as to inactivate each other, but probably the “interfering” drugs modify the characteristics of the bacterial population so as to make it less susceptible to penicillin action. WHAT Is THE METABOLIC ANOMALY IN PERIODIC PARALYSIS? Frank H. 7yler,* Department of Medicine, University of Utah, College of Medicine, Salt Lake City, Utah. Since the ol,servation was made that hypo- kaliemia is associated with the attacks of weak- ness in certain patients having periodic paralysis, it has been widely assumed that the fundamental metabolic anomaly is one of potassium me- tabolism. We have observed a family in which thirty-three patients with clinically typical periodic paralysis are known and in whom the attacks have not been associated with hy- pokaliemia. The trait shows dominant in- heritance. Microscopically, the muscle fibers show vacuolization. In spite of the production of serum levels of 3.0 mEq. of potassium per L. by the simultane- ous administration of insulin and glucose no change in muscular strength was observed. In addition, the failure of these patients to improve on oral potassium suggests that this periodic paralysis is different in its fundamental mecha- nism from other examples of the disorder. However, the poor correlation between the level of serum potassium and degree of paralysis in other cases reported in the literature as well as certain other findings raises the possibility that serum potassium depletion is not the primary mechanism in those cases as well. HISTOLOGIC STUDIES OF THE NORMAL AND DIS- EASED KIDNEY UTILIZING A NEW TECHNIC FOR DEMONSTRATION OF ACID MUCOPOLYSAC- CHARIDES AND OTHER ELEMENTS OF CONNEC- TIVE TISSUE. James F. Rinehart * and Suleiman Abul-Haj, Department of Pathology, Uni- versity of California School of Medicine, San Francisco, Calif. In disease, abnormalities of the mucopolysac- charide ground substance appear to be im- portantly involved particularly in rheumatic diseases and arteriosclerosis. In 1947 Hale described a method for histologic demonstration of the mucopolysaccharides based upon the affinity of the materials for colloidal iron. The method lacked selectivity and histologic clarity. We have modified the method in such a manner that the acid mucopolysaccharide can be clearly demonstrated and with appropriate counterstaining the other important element of the connective tissue including collagen, reticu- lum and basement membranes can be differen- tiated in a single preparation. The technic has proved particularly useful in the study of the kidney. This report is concerned with the de- AMERICAN JOURNAL OF MEDICINE

What is the metabolic anomaly in periodic paralysis?

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Page 1: What is the metabolic anomaly in periodic paralysis?

Western Society for Clinical Research

The incidence of significant circulating anti- toxin one month after two injections in twenty- one patients and the incidence of Schick nega- tivity three months after three injections in all patients will be reported. ANTIBIOTIC ANTAGONISM: THE INTERFERENCE OF

CHLORAMPHENICOL, AUREOMYCIN AND TER- RAMYCIN WITH THE ACTION OF PENICILLIN IN EXPERIMENTAL INFECTIONS AND IN VITRO. E. Jawete, * J. B. Gunnison and R. S. Speck, Division of Bacteriology, University of Cali- fornia, School of Medicine, San Francisco, Calif. Antagonistic effects between the three “newer”

antibiotics and penicillin have been demon- strated in oitro and in experimental infections of mice with both gram positive (hemolytic strep- tococcus) and gram negative (Klebsiella pneu- moniae) organisms. The antagonism between penicillin and either chloramphenicol, aureo- mycin or terramycin extends over considerable ranges of concentrations of each drug, including concentrations commonly achieved in human body fluids with therapeutic doses. The phe- nomenon is limited by the degree of anti- microbial activity of each drug: Concentrations below the bacteriostatic level for a given micro- organism as well as concentrations possessing marked bactericidal activity are without inter- fering effect.

Antibiotic antagonism is observed in experi- mental infections when the drugs are given at the same or different sites, in single or multiple doses. However, antagonism occurs only if chloramphenicol, aureomycin or terramycin are administered simultaneously with or prior to penicillin, not if penicillin is given first. Certain drugs which are synergistic with penicillin, e.g., streptomycin or bacitracin, can overcome anti- biotic antagonism.

The experimental evidence indicates that the phenomenon is not one of mutual antagonism between the drugs concerned but rather an interference of chloramphenicol, aureomycin or terramycin with the early bactericidal and therapeutic effects of penicillin. The antagonistic drugs do not appear to interact physically or chemically so as to inactivate each other, but probably the “interfering” drugs modify the characteristics of the bacterial population so as to make it less susceptible to penicillin action. WHAT Is THE METABOLIC ANOMALY IN PERIODIC

PARALYSIS? Frank H. 7yler,* Department of

Medicine, University of Utah, College of Medicine, Salt Lake City, Utah. Since the ol,servation was made that hypo-

kaliemia is associated with the attacks of weak- ness in certain patients having periodic paralysis, it has been widely assumed that the fundamental metabolic anomaly is one of potassium me- tabolism. We have observed a family in which thirty-three patients with clinically typical periodic paralysis are known and in whom the attacks have not been associated with hy- pokaliemia. The trait shows dominant in- heritance. Microscopically, the muscle fibers show vacuolization.

In spite of the production of serum levels of 3.0 mEq. of potassium per L. by the simultane- ous administration of insulin and glucose no change in muscular strength was observed. In addition, the failure of these patients to improve on oral potassium suggests that this periodic paralysis is different in its fundamental mecha- nism from other examples of the disorder. However, the poor correlation between the level of serum potassium and degree of paralysis in other cases reported in the literature as well as certain other findings raises the possibility that serum potassium depletion is not the primary mechanism in those cases as well. HISTOLOGIC STUDIES OF THE NORMAL AND DIS-

EASED KIDNEY UTILIZING A NEW TECHNIC FOR DEMONSTRATION OF ACID MUCOPOLYSAC- CHARIDES AND OTHER ELEMENTS OF CONNEC- TIVE TISSUE. James F. Rinehart * and Suleiman

Abul-Haj, Department of Pathology, Uni- versity of California School of Medicine, San Francisco, Calif. In disease, abnormalities of the mucopolysac-

charide ground substance appear to be im- portantly involved particularly in rheumatic diseases and arteriosclerosis. In 1947 Hale described a method for histologic demonstration of the mucopolysaccharides based upon the affinity of the materials for colloidal iron. The method lacked selectivity and histologic clarity. We have modified the method in such a manner that the acid mucopolysaccharide can be clearly demonstrated and with appropriate counterstaining the other important element of the connective tissue including collagen, reticu- lum and basement membranes can be differen- tiated in a single preparation. The technic has proved particularly useful in the study of the kidney. This report is concerned with the de-

AMERICAN JOURNAL OF MEDICINE