4.06 Southern Society for Clinical Research

beta globulin. He obtained a partial remission during the first treatment period but relapsed after three months. Urethane was then given continuously, 1,275 gm. in fourteen months. He relapsed under treatment and urethane was dis- continued. The excretion of Bence Jones protein in the urine then declined from an average of 17 to 19 gm. per day to 0.25 to 0.4 gm., serum protein with the mobility of the abnormal com- ponent fell from 2.35 gm. to 1.0 gm. per 100 CC. and the hemoglobin which had fallen below 6.0 gm. per 100 cc. was again maintained at normal levels.

In one of the four patients with a virtually normal serum protein pattern a definitely ab- normal peak developed during an exacerbation of his disease after being followed for seventeen months. In another patient heavy Bence Jones proteinuria was reduced 75 per cent without altering the serum protein pattern.

As plasma cell growth is inhibited by urethane in multiple myeloma, abnormal serum protein components, even those generally found not to represent Bence Jones proteinemia, are reduced or may virtually disappear. This change parallels the reduction or disappearance of Bence Jones proteinuria. During prolonged continuous ad- ministration of urethane myeloma cells may become dependent on the chemical. CEREBRAL METABOLISM IN HYPERTHYROID-

ISM AND MYXEDEMA. Peritz Scheinberg, M.D. (introduced by Eugene A. Stead, Jr., M.D.). Durham, N.C. (From the Duke University School of Medicine.) Cerebral blood flow and metabolism were

measured by means of the nitrous oxide technic in nine subjects with hyperthyroidism and in eight subjects with myxedema. Three patients with myxedema were restudied after clinical improvement on thyroid therapy.

The subjects with hyperthyroidism showed no significant variation from normal in any of the measured cerebral metabolic functions. This is of interest in view of the 35 per cent increase in splanchnic oxygen consumption known to occur in a similar series of hyperthyroid patients.

The patients with myxedema showed reduc- tions in cerebral blood flow (38 per cent) and oxygen consumption (27 per cent) commensu- rate with the fall in cardiac output and total oxygen consumption which occurs in these pa- tients. Cerebral glucose consumption decreased in proportion to the cerebral oxygen consump- tion. Cerebral vascular resistance was increased almost 100 per cent. All cerebral metabolic

functions returned toward normal along with clinical improvement in the three patients re- studied after thyroid therapy.

These data indicate that in hyperthyroidism the brain does not share in the general increase which occurs in body metabolism and that the clinical signs of mental dysfunction so commonly observed in myxedema may be accounted for by the decreased cerebral metabolism in this disease. PATHOCENESIS OF JARISCH-HERXHEIMER RE-

ACTION IN RABBIT SYPHILIS: PRODUCTION BY THE INJECTION OF SYPHILITIC SERUM. Walter H. Sheldon, M.D., Albert Heyman,

M.D. and (by invitation) Lilian D. Evans,

M.D. Atlanta, Ga. (From the Departments

of Pathology and Medicine, (Clinic for

Genitoinfectious Diseases), Emory Uni-

versity School of Medicine, and Grady

Memorial Hospital.) Previous studies have shown that transient

acute inflammatory changes occur in human syphilitic lesions during the Herxheimer reac- tion. Similar histologic changes occur in syphi- litic lesions of rabbits following treatment. Injec- tions of living or dead spirochetes failed to produce these changes.

Herxheimer-like reactions occur in Spirillum minus. infections in which immobilizing and lysing antibodies are present. This infection pro- duces skin lesions in rabbits. When serum from similarly infected rabbits was given, the recipi- ent animals showed histologic changes in the lesions resembling the changes occurring in the Herxheimer reaction of syphilis.

Twelve rabbits were inoculated intravenously and in multiple skin sites with Treponema pal- lidum, Nichols strain. After lesions appeared each of the six animals was given 70 cc. of serum intravenously from untreated syphilitic rabbits. The remaining animals received equal amounts of normal rabbit serum. Individual syphilomas were excised from each animal before and after injection. On histologic examination transient acute inflammatory changes were found in the syphilomas of five animals receiving syphilitic serum. No changes were observed in the six controls.

Our findings suggest a relationship of serum antibodies in syphilitic and Spirillum minus in- fections to the mechanism of the Herxheimer reaction. Further studies on this problem are in progress.

STUDIES ON AN HOMOI.OGOUS BRAIN TISSUE

ANTIGEN IN DOGS. Lezcis Thomas, -M.D.>

AMERICAN JOURNAL OF MEDICINE

Southern Society for Clinical Research 407 (and by invitation) Philip Y. Paterson, M.D. and Elizabeth Smithwick, M.D. New Or- leans, La. (From the Division of Infec-

tious Disease, Department of Medicine, Tulane University School of Medicine.) Allergic encephalomyelitis has been produced

in dogs by immunization with homologous brain extracts mixed with adjuvants. The histo- pathology of the disease resembles that described by others in monkeys but a longer time is re- quired for the development of lesions and the incidence is lower. An antibody has been demon- strated in the serum of immunized dogs which reacts with an antigenic component of normal dog brain and peripheral nerve in complement fixation tests. The relationship between this antigen-antibody system and the experimental disease is not known; all dogs showing demye- lination have had antibody but others without lesions have also had antibody.

The antigen is demonstrable in aqueous and lipid-solvent extracts of brain. It is present in brain and nerve tissue from other species but not in other organs. It is not demonstrable in new- born dog brain tissue. It is resistant to boiling and to treatment with 10 per cent formalin. It is a component of the acetone-soluble, unsaponi- fiable fraction of white matter lipids and is separable from cholesterol. Specific immunologic activity may be demonstrated with less than 1 microgram of the partially purified material. Further studies bearing on the nature of this material will be presented. EFFECTS OF POSTURE AND OF COMPRESSION

(OF THE NECK ON GLOMERULAR FILTRA- :TION. William Viar, M.D. and Thomas Lombardo, M.D. (introduced by T. R. Harri- son, M.D.). Dallas, Tex. (From the De-

partment of Medicine, Southwestern

Medical College.) The rise in sodium excretion produced by the

recumbent position or by compression of the neck in the sitting position is not attended by significant change in glomerular filtration. Alter- ations in tubular activity must therefore be held responsible. RELATIONSHIP UF DURATION OF PHASES w

CARDIAC CYCI.E LENGTH AS DETERMINED IN HUMANS BY THE ELECTROKYMOGRAPH. kathryn Willis, M.D. (introduced by Tin&y R. Harrison, M.D.). Dallas, Tex. (From the Department of Internal Medicine,

Southwestern Medical College.) There is a paucity of data in the literature

SEPTEMBER, 1950

of the duration of phases of the cardiac cycle in human subjects. Therefore, it seems worth while to present the duration of these phases and relation to cycle length as determined in ,normal subjects by the electrokymograph. The average values are, namely, isometric contraction 0.039 second, rapid ejection 0.104 second, total sys- tole 0.26 second, protodiastole (time from relaxa- tion of ventricle to closure of semilunar valve) 0.039 second, as measured from tracings of ascending aorta in thirty-two normal subjects. Diastolic phases measured from left ventricular border tracings are the following: isometric relaxation 0.104 second, rapid filling 0.135 sec- ond and diastasis 0.16 second. Ranges OF these values are to be presented as well as comparison to total cardiac cycle length. TREATMENT OF INFECTIONS DUE TO PSEUDO-

MONAS ~~ERUCINOSA (BACILLUS PYOCY- ANEUS) WITH POLYMYXIN-REPORT OF A CASE OF MENINGITIS. Ellard M. Tow, M.D. and E. R. Hayes, M.D.) (introduced by James A. Greene, M.D.). Minneafiolis, Minn. (From the Department of Medicine, Baylor University College of Medicine,

Houston, Texas and Students’ Health Service, University of Minnesota.) Polymyxin is a polypeptide antibiotic which

acts as a bactericidal agent against Aerobacter aerogenes, Sal. typhosa, K. pneumoniae, H. in- fluenzae, and Pseudomonas aeruginosa but not against Proteus vulgaris. It is composed of five fractions having similar chemical and biologic properties but varying somewhat in toxic mani- festations. Because of evidences of nephrotoxicity and neurotoxicity occurring in some patients, as well as the overlapping antibacterial spectrum of other antibiotic agents, its general use has been limited. Infections due to Pseudomonas aeruginosa, however, frequently do not respond to other available antimicrobial agents. Clinical experience thus far has revealed a consistently favorable response in patients with Pseudomonas infections treated with polymyxin. Conse- quently, it is believed that because of the high mortality rate associated with systemic infections due to this organism, polymyxin represents the most successful means of treatment available at the present time.

A case of meningitis due to Pseudomonas aeruginosa occurring in a sixteen year old girl following spinal anesthesia, failing to respond to sulfonamide, penicillin and streptomycin therapy but responding to the intramuscular and intra- thecal administration of polymyxin, is discussed.