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The object of this investigation was to evaluate the use of aureomycin in obstetric patients. Since the advent of the sulfonamide drugs and penicillin investigators have continued to search for new antibiotics which would be effective and less toxic. One of the products of this search, aureomycin, was discovered by Duggar in 1948.1 Extensive bacteriologic and clinical studies have established the effectiveness of this agent in a wide variety of infections. Its mode of action, as determined in vitro, is predominately bacteriostatic, but it also possesses bactericidal properties at high concentration. Because of the promising results reported with aureomycin, including its use in obstetric complications,2 a study of this drug and its effect on the bacteriologic flora and infections during pregnancy and the puerperium was believed warranted. MATERIAL AND METHODS Aureomycin was prescribed according to various dosage schedules as noted under the individual descriptions. The in vitro studies

Primary atypical nonbacterial pneumonia has been reported with increasing frequency during the past fifteen years.1 This disease has since received particular attention. The intensive studies on disease of the respiratory tract conducted during World War II served to differentiate "primary atypical pneumonia" from similar pulmonary infections of established bacterial, viral or rickettsial causes.2 Clinically, diseases caused by the viruses of influenza, psittacosis, ornithosis and the rickettsiae of Q fever resemble atypical pneumonia.2 No causative agent has been isolated from patients suffering from this disease, although pooled sputum from patients has been shown to be capable of inciting the disease in human volunteers, even after it was passed through Corning sintered glass or Seitz filters.3 At present, there is no specific laboratory procedure available for confirming the clinical diagnosis. It has been noted that cold hemagglutinins and agglutinins for Streptococcus MG often develop in the serum of

Aureomycin is an antibiotic derived from a strain of Streptomyces aureofaciens).1 It has been found to protect mice and guinea pigs infected with the rickettsia of Q fever, Rocky Mountain spotted fever, murine typhus and rickettsial pox.2 The drug is readily absorbed after oral administration. Although quantitative assay in the body fluids has not been satisfactory, low levels (0.3 to 2.5 micrograms per millimeter) have been detected in the blood serum and levels up to 320 micrograms per milliliter3 in the urine. Pharmacologic studies in animals have shown that the toxicity of the drug is low except after intravenous administration where hemoglobinuria and anemia have been noted.4 In human beings, therapeutic doses up to 60.0 milligrams per kilogram of body weight per day given orally have not been associated with any toxic manifestations except for occasional nausea and vomiting.5 The latter has been transient and

An analysis of some of the physiological factors active in Maitland tissue cultures has been presented in the hope that it may be of some value in clarifying the principles underlying tissue cultures in general. It has been found that the empirically determined necessity of using relatively small amounts of tissue in such cultures is dependent upon the fact that excessive tissue leads to a rapid change of reaction toward the acid side. Whereas tissue may remain viable in an environment as alkaline as pH 9 and over, viability is rapidly destroyed when the reaction approaches pH 6. Evidence is presented to indicate that the changes in electrode potentials which take place in Maitland cultures are not, as has been suggested, the determining factors upon which virus multiplication depends, although they may, of course, be incidentally important. It has been shown that there are fundamental differences between those conditions in Maitland cultures which favor the multiplication of a typical virus and those upon which the growth of the Rickettsiae of typhus fever depends. The virus which we have studied (equine encephalitis virus, western type) multiplies during the period of active tissue metabolism. The maximum virus titrations are obtained at about the time at which metabolism has come to a standstill. Thereafter the virus not only ceases to increase but rapidly deteriorates. The period of viability of the tissue cells themselves is shortened by several days in the presence of virus multiplication. There is some evidence that a temporary acceleration of oxygen uptake takes place during the time of active virus multiplication. Technical difficulties in controlling such experiments prevent certainty in regard to this point. In contrast with the conditions determining the growth of a virus agent in the Maitland cultures the multiplication of Rickettsiae does not begin to any determinable extent until after active cell metabolism has either become stabilized or has ceased. The Rickettsiae continue to grow at a time when the cells are no longer viable. It appears likely that these organisms find the most favorable conditions for growth in cells which are no longer metabolically active but in which some delicately heat-susceptible elements have not yet been disturbed. As a consequence of these observations, frozen and preserved embryonic tissues have been successfully used for Rickettsia cultivation. A report on these experiments will be made in a separate communication.

The presence of riboflavin, pantothenic acid, and biotin could not be demonstrated in significant amounts in moderately concentrated solutions of purified tobacco-mosaic virus.

Local tetanus limited to one leg was studied in cats after intramuscular injection of tetanus toxin. 1. The electric and mechanical response of the affected muscle after a single stimulus to the intact sensory-motor nerve is greater in amplitude and duration than the response of the corresponding muscle of the unaffected leg (Fig. 1). 2. This augmented response of the muscle is associated with an augmented response arising from the ipsilateral portion of the spinal cord, while the contralateral part of the cord is unaffected, as demonstrated by electrographic records from the motor nerves (Figs. 2 to 5). 3. The augmented muscular response is abolished when the reflex arc is broken, but the augmented response in the spinal cord is independent of changes in the muscle, the neuromuscular junction, the afferent and efferent peripheral nerves, and the dorsal root ganglia. 4. The augmented spinal response develops in the absence of the peripheral signs of local tetanus. Hence the pathogenesis of the altered state in the spinal cord is independent of the peripheral effects of the toxin. 5. In local tetanus, therefore, the toxin injected intramuscularly acts selectively upon the segments of the spinal cord which supply the innervation of the injected area. 6. The augmented spinal response may be prevented by section of the nerve trunks supplying the area of injection prior to the injection of the toxin. 7. It is concluded that in local tetanus the toxin is carried to the spinal cord by way of peripheral nerves.

The potent folic acid antagonists, aminopterin (4-amino folic acid) and amethopterin (4-amino-N10-methyl folic acid) are being extensively employed for the amelioration of certain types of leukemia and other neoplastic diseases.1 These antimetabolites induce a folic acid deficiency, manifested in patients by gastrointestinal cramps, diarrhea, hemorrhage, ulceration of the palate and oral mucous membranes, leukopenia, which may progress to an aplastic anemia, and alopecia. The appearance of these toxic manifestations may be delayed, and the cumulative toxic dose of drug may be exceeded before signs of toxicity become evident. For this reason, the dosage employed of these aminosubstituted derivatives of folic acid is often less than that necessary for therapeutic efficacy. These toxic manifestations have not been reversible clinically when folic acid, liver extract or vitamin B12 has been administered. Experimental observations have demonstrated that under certain specific conditions folic acid can completely prevent but not reverse

The nonepidemic occurrence of typhus among residents of New York City was first reported by Brill in 1898.1 A singular selection of persons who had been born in Eastern Europe was described. Later investigations conducted by Maxcy in the Southeastern United States of what was believed to be Brill's disease revealed that endemic typhus in this country was caused by a murine strain of Rickettsia transmitted by the rat flea and was not the louse-borne epidemic type.2 In 1933 and 1934, Zinsser, through careful epidemiologic analysis of data assembled in New York and laboratory studies on cases observed in Boston, postulated that Brill's disease was probably a recrudescence of epidemic louse-borne typhus and not the endemic flea-borne type observed in Southeastern United States.3 The strains isolated by Zinsser from 3 patients behaved like the European type and supported the belief that Brill's disease represented the classic European

Aureomycin is an antibiotic derived from a strain of Streptomyces aureofaciens. It is supplied as a yellow crystalline hydrochloride salt which is soluble in distilled water but somewhat less soluble in isotonic sodium chloride solutions. These solutions are acid (pH 4.5). The activity of the antibiotic deteriorates rapidly in alkaline solution at room temperature.IN VITRO STUDIESAureomycin has been shown to possess antibacterial activity against numerous gram-positive and gram-negative bacteria. Beta hemolytic streptococcic strains, groups A. D, F and G, and three strains of Streptococcus faecalis were susceptible to the effects of 0.3 to 1.25 micrograms of aureomycin per milliliter; Diplococcus pneumoniae types I, II and III were susceptible to 0.1 to 0.3 microgram, staphylococci to 0.6 microgram per milliliter, strains of Bacillus coli aerogenes to 5.0 micrograms per milliliter; Klebsiella pneumoniae to 1.0 to 5.0 micrograms per milliliter, Hemophilus influenzae to 2.0 micrograms per milliliter, and Brucella

In May 1947, Benedict and Langlykke1 reported that sterile culture filtrates of Bacillus polymyxa in dilutions of 1:1,000 inhibited the growth of Brucella bronchiseptica in culture. Shortly after this report, Stansly, Shepherd and White2 independently described the isolation of an antibiotic substance from B. polymyxa which they named "polymyxin." This antibiotic was shown by them to be effective only against gram-negative organisms in vitro, and to possess a high degree of therapeutic activity against experimental infections produced in mice by the inoculation of Klebsiella pneumoniae or Pasteurella multocida. It was also effective against experimental fowl typhoid infections in chicks. Subsequently, Stansly and Schlosser3 established the identity of polymyxin as a new antibiotic and developed a method for its bio-assay. Not long after the two original reports on this antibiotic appeared, Ainsworth, Brown and Brownlee4 announced that they had isolated an antibiotic, active against gram-negative organisms, from

The sulfhydryl content of serum proteins has been quantitatively determined through an adaptation of an amperometric titration. Among normal adults, the values noted, expressed as milligrams of cysteine, were uniform, reproducible and averaged 6.5±0.2 mg per 100 ml serum or 5.5±0.3 mg per gram serum nitrogen. The albumin component of serum contained 80% of the total sulfhydryl. The addition of desoxyribonucleic acid, creatine or formaldehyde did not change the sulfhydryl content of the serum. The addition of an SH reagent such as para-chloro-mercuri-benzoate abolished all reactant groups measured with this method.Sera obtained from patients with various diseases showed a significant reduction in the sulfhydryl available for this titration. This quantitative reduction in sulfhydryl was still evident when corrected for differences in the albumin and globulin components and thus represented a qualitative change in the serum proteins. At the present time, the alteration in the sulfhydryl content of serum or its components is not characteristic enough to permit specific differentiation among the neoplastic, metabolic, or infectious diseases. The possible application of serial serum sulfhydryl determinations in animals and patients may be of value as an objective indicator of response and for study of the mechanism of action of chemotherapeutic and other agents.

Through the use of a medium containing tyrothricin in a concentration inhibitory to Gram positive cocci, isolation of H. influenzaefrom the nasopharynx may be facilitated. This medium is being tested in epidemiological surveys now in progress.

Until recently the problem of the proper antibiotics to use in the treatment of infectious diseases was comparatively simple. The physician who was faced with an infectious disease in which antibiotic systemic therapy was indicated administered either penicillin or streptomycin or both, and that was that. During the past year this relatively happy state of affairs has been rudely interrupted by the appearance of aureomycin and chloramphenicol (chloromycetin®), two antibiotics which possess wide and effective ranges of action. The result is that careful attention must now be given to the choice of the antibiotic to be used in the treatment of any individual patient, and in certain instances of disease the problem becomes one of choosing the most effective combination of the several antibiotics.It will be our purpose in this report to attempt to assess current information concerning the choice of antibiotics, to propose adequate dosage schedules and to

Generalized North American blastomycosis is generally a fatal disease. Iodine or x-ray therapy may cause a temporary recession of the lesion. In 1945 Elson1 reported that certain of the diamidines exerted a fungistatic effect on Blastomyces dermatitidis in vitro. This observation had been noted and discussed by one of us2 in a review on the pharmacology, mode of action, and therapeutic possibilities of the aromatic diamidines. When the patient suffering from systemic blastomycosis, whose case history will subsequently be described, was admitted to the Veterans Administration Hospital at Ft. Howard, Md., it was deemed advisable to treat him with two of the diamidines. REPORT OF A CASE A 33-yr.-old Indian was admitted to another hospital on July 15, 1950. He complained of difficulty in swallowing for about one year. Dysphagia had been so severe during the previous five months that he had lost about 40 lb. (18.1 kg.)

Crystalline penicillin G has been proposed as the remedy of choice with sulfadiazine as alternate in the treatment of actinomycosis.1 The two agents have also been used in combination. Streptomycin,2 bacitracin,3 and aureomycin4 have also been reported to be efficacious. The observation that "stilbamidine" (4,4′-stilbenedicarboxyamidine) was a useful therapeutic agent for infections caused by Blastomyces dermatitidis5 prompted its use in a patient with actinomycosis resistant to prolonged administration of penicillin and sulfadiazine.REPORT OF A CASEA 51-year-old white man was admitted to the Veterans Administration Hospital on Jan. 4, 1951, with a mass in the left submental region that had appeared after extraction of a tooth in November, 1950. The tumor had become progressively larger. Pain in the right side of the chest and a cough had been treated by the patient's physician with aureomycin for two days. The patient lost 9 lb. (4.1