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Effect of antibiotics on intestinal absorption of vitamin B12 in disorders of the gastrointestinal tract
Western Society for Clinical Research negative results in the pregnant group exceeds those in the non-pregnant group by 10 per cent, a statistically significant difference. In order to rule out possible primary syphilis at the time of the initial negative TPI result, second samples were submitted approximately three months later. Results varied in only one case in which an initially doubtful TPI test subsequently became positive. Standard serologic tests for syphilis were performed on the same serum sample in 169 of the pregnant women who gave negative TPI results. Ninety-seven still gave positive reactions in one or more of the tests, and sixty-six had reverted to negative results. Anticomplementary reactions were obtained only in six specimens. The standard serologic tests for syphilis on serum from 295 pregnant women in whom the TPI gave negative results indicated a low degree of specificity for the serologic tests for syphilis. DIAGNOSISOF POLIOMMLITISBY TIWJE CULTURE. William M. M. Kirby” and Charles A. Evans. Dept.
Medicine and Microbiology, Univ. Washington School of Medicine, Seattle, Wash. Utilizing trypsinizcd monkey kidney cells, stool specimens from more than sixty patients admitted to King County Hospital since July 1954, have been tested for the presence of poliomyelitis virus. Virus has been recovered from more than 80 per cent of the paralytic cases and from approximately 30 per cent of the non-paralytic cases. Of special interest are (1) the occurrence of an unusually large number of type III (Leon) infections and (2) the recovery from at least six patients of viruses which are not neutralized by any of the three types of poliomyelitis antisera. IN VITRO SUSCEPTIBILITY OF PROTEUS TO ANTIBIOTIC AGENTS. William L. Hewitt, * Charles B. Stone and Sidney Finegold. Los, Angeles, Calif.
The pattern of antibiotic sensitivity of approximately 100 strains of proteus isolated from clinical sources has been studied employing a serial dilution technic. Accepting the fact that the sensitivity of proteus to any agent is not of a high order, two large groups have been delineated, (1) a penicillin-sensitive, broad spectrum antibiotic-resistant group (6 per cent of the strains in this group were sensitive to chloramphenicol but resistant to tetracycline) and (2) a penicillin-resistant, broad spectrum antibiotic-sensitive group. The relation of species classification to antibiotic sensitivity AUGUST,
1955
classification will be discussed. On a weight basis chloramphenicol was more effective than tetracycline. Fifty three per cent of the strains were sensitive to 12.5 pg. per ml. or less of the former agent and 19 per cent of the latter. Tetracycline was as effective or more so than oxytetracycline in all instances. Only 4 per cent of the strains were sensitive to neomycin or to streptomycin. Because of the relative resistance of these bacteria to single agents, in vitro studies with combinations of antibiotics were undertaken. If one-fourth or less of the effective concentration of each single antibiotic would prevent growth when combined, a significant additive effect was assumed to occur. Among the penicillin-sensitive strains significant additive effects were observed with combinations of penicillin-neomycin (90 per cent of strains) and with chloramphenicol-neomycin (77 per cent) in spite of the relative resistance to neomycin alone. In many instances the increased antibacterial effect was quite striking. Among the penicillin resistant strains significant effects were observed with tetracycline-neomycin (83 per cent) and with chloramphenicol-neomycin (60 per cent). PROTEOLYTIC ENZYME INHIBITION. Frederic C. Mall. * Univ. Washington School Medicine,
Seattle,
Wash.
The proteolytic enzyme extracted from white blood cells is inhibited by serum. The variations in this serum inhibitor have been studied in Macacus rhesus monkeys. During control periods the serum inhibitor level is constant and of low magnitude. Upon stressing the animal by a sterile abscess, the inhibitor level promptly rises during the period of inflammation. A similar rise occurs following the administration of hydrocortisone followed by a slow fall to within normal limits. In adrenal insufficiency produced by sudden cessation of cortisone therapy, the sterile abscess is not followed by rapid rise of the serum inhibitor as under normal circumstances. These observations suggest that the level of white cell proteolytic enzyme inhibitor level in serum is controlled in part through adrenal hormones and that it responds quickly to stress in the normal animal. This inhibitor response may explain in part the anti-inflammatory action of cortisone. EFFECT OF ANTIBIOTICSON INTESTINALABSORPTION OF VITAMIN B12 IN DISORDERS OF THE GASTROINTESTINALTRACT. James A. Halsted, *
298
Western
Society for Clinical Research
Marian E. Swendseid, Marvin Gasster and Peter M. Lewis. Los Angeles, Calif.
By subtracting the fecal radioactivity, determined with a scintillation counter, from the amount present in a test dose of cobaltso-labeled vitamin Blz administered orally, intestinal absorption of this vitamin can be determined with reasonable quantitative accuracy. The effect of various agents on absorption, such as intrinsic factor preparations or antibiotics, can be measured. Using a test dose of 0.5 kg. of Coso-Bi2 the average amount absorbed in eleven normal individuals was 68 per cent. In ten patients with various diseases of the small intestine 24 per cent was absorbed. In eight patients with pernicious anemia and in twelve patients who had had total gastrectomies there was essentially no absorption. Concomitant administration of intrinsic factor with the test dose had no effect in normal patients nor patients with small intestine disease, but in the pernicious anemia and total gastrectomy subjects absorption became normal in each instance. The effect of aureomycin@ or achromycin@ on the absorption of vitamin Bi2 was determined in six patients with pernicious anemia, in four patients who had had total gastrectomies and in ten patients with small intestine disease. Two tests were performed in each patient during the administration of two grams of the antibiotic daily. There was no effect on absorption in any of the patients with pernicious anemia, nor in any of the total gastrectomy group. Three of the patients with small intestine disease had megaloblastic anemia associated with intestinal anastomoses and stasis of intestinal contents. In these patients a very significant increase in absorption of Coeo-Bis occurred. Of the other seven patients two had non-tropical sprue, four had regional enteritis and one had steatorrhea due to pancreatic insufficiency. Although absorption of Bi2 was impaired in each of these seven, antibiotic administration did not result in increased absorption. The relationship of antibiotics to vitamin Blz utilization and to hematopoiesis will be discussed in the light of these findings. SERUM TRANSAMINASELEVELS IN MYOCARDIAL INFARCTION. Clarence M. Agress,* Albert A. Kattus and John S. La Due. Cardiovascular and Cardiology Lab., Gen. Medical Research
Service, V. A. Center; the Dept. of Medicine, Univ. California Medical Center, Los Angeles, Calif., and the Sloan Kettering Inst. Dept. Medicine, Memorial Center, New York, N. Y. Clinical studies by one of the authors (La Due) have shown that the serum level of transaminase rises significantly following acute myocardial infarction. This work indicated that a study of this kind in dogs, where varied amounts of infarction could be produced and more accurately followed, would prove valuable. The coronary arteries of thirteen closed-chest dogs were embolized with plastic microspheres. Twelve-lead electrocardiograms were used to follow the course of the infections and color photographs were taken of the hearts at autopsy. Serum samples were taken every four hours for the first twenty-four to thirty-six hours and some dogs were followed for seventy-two hours. The results showed that in all cases the serum transaminase level rose sharply after myocardial infarction, reaching a peak between twelve to eighteen hours after embolization. There was a relatively linear correlation between the peak serum transaminase level and the amount of myocardial infarction as estimated at autopsy. A clinical study is being carried out at the Veterans Administration Center, Los Angeles; thus far 197 determinations have been made in sixty-four patients. Eleven were controls in which the highest level was twenty-four transaminase units. A miscellaneous group, including congestive heart failure, cerebrovascular accidents, old infarcts in five patients and pericarditis in four patients were in the normal range. Peak values of thirteen patients with acute myocardial infarction ranged from 40 to 580 transaminase units. In coronary insufficiency patients, as differentiated from myocardial infarction patients, serum transaminase levels were useful in fourteen of seventeen cases. IKFLUENCEOF BLOOD TRANSFUSIONS UPON THE CIRCULATING PLATELETS IN ARTERIAL AND VENOUS BLOOD OF MAN. H. R. Bierman,* Keith H. Kelly, and Fauno L. Cordes. Hosp. Tumors and Allied Diseases, Div. Research, City of Hope Medical Center, Duarte, Calif. It has been shown by Harrington et al. that the blood or plasma of patients with idiopathic thrombocytopenic purpura (ITP) infused into volunteers will cause a thrombocytopenia in the venous blood. Prompt fall in the venous platelet level within fifteen to thirty minutes after the AMERICAN
JOURNAL
OF
MEDICINE
Medicine and Microbiology, Univ. Washington School of Medicine, Seattle, Wash. Utilizing trypsinizcd monkey kidney cells, stool specimens from more than sixty patients admitted to King County Hospital since July 1954, have been tested for the presence of poliomyelitis virus. Virus has been recovered from more than 80 per cent of the paralytic cases and from approximately 30 per cent of the non-paralytic cases. Of special interest are (1) the occurrence of an unusually large number of type III (Leon) infections and (2) the recovery from at least six patients of viruses which are not neutralized by any of the three types of poliomyelitis antisera. IN VITRO SUSCEPTIBILITY OF PROTEUS TO ANTIBIOTIC AGENTS. William L. Hewitt, * Charles B. Stone and Sidney Finegold. Los, Angeles, Calif.
The pattern of antibiotic sensitivity of approximately 100 strains of proteus isolated from clinical sources has been studied employing a serial dilution technic. Accepting the fact that the sensitivity of proteus to any agent is not of a high order, two large groups have been delineated, (1) a penicillin-sensitive, broad spectrum antibiotic-resistant group (6 per cent of the strains in this group were sensitive to chloramphenicol but resistant to tetracycline) and (2) a penicillin-resistant, broad spectrum antibiotic-sensitive group. The relation of species classification to antibiotic sensitivity AUGUST,
1955
classification will be discussed. On a weight basis chloramphenicol was more effective than tetracycline. Fifty three per cent of the strains were sensitive to 12.5 pg. per ml. or less of the former agent and 19 per cent of the latter. Tetracycline was as effective or more so than oxytetracycline in all instances. Only 4 per cent of the strains were sensitive to neomycin or to streptomycin. Because of the relative resistance of these bacteria to single agents, in vitro studies with combinations of antibiotics were undertaken. If one-fourth or less of the effective concentration of each single antibiotic would prevent growth when combined, a significant additive effect was assumed to occur. Among the penicillin-sensitive strains significant additive effects were observed with combinations of penicillin-neomycin (90 per cent of strains) and with chloramphenicol-neomycin (77 per cent) in spite of the relative resistance to neomycin alone. In many instances the increased antibacterial effect was quite striking. Among the penicillin resistant strains significant effects were observed with tetracycline-neomycin (83 per cent) and with chloramphenicol-neomycin (60 per cent). PROTEOLYTIC ENZYME INHIBITION. Frederic C. Mall. * Univ. Washington School Medicine,
Seattle,
Wash.
The proteolytic enzyme extracted from white blood cells is inhibited by serum. The variations in this serum inhibitor have been studied in Macacus rhesus monkeys. During control periods the serum inhibitor level is constant and of low magnitude. Upon stressing the animal by a sterile abscess, the inhibitor level promptly rises during the period of inflammation. A similar rise occurs following the administration of hydrocortisone followed by a slow fall to within normal limits. In adrenal insufficiency produced by sudden cessation of cortisone therapy, the sterile abscess is not followed by rapid rise of the serum inhibitor as under normal circumstances. These observations suggest that the level of white cell proteolytic enzyme inhibitor level in serum is controlled in part through adrenal hormones and that it responds quickly to stress in the normal animal. This inhibitor response may explain in part the anti-inflammatory action of cortisone. EFFECT OF ANTIBIOTICSON INTESTINALABSORPTION OF VITAMIN B12 IN DISORDERS OF THE GASTROINTESTINALTRACT. James A. Halsted, *
298
Western
Society for Clinical Research
Marian E. Swendseid, Marvin Gasster and Peter M. Lewis. Los Angeles, Calif.
By subtracting the fecal radioactivity, determined with a scintillation counter, from the amount present in a test dose of cobaltso-labeled vitamin Blz administered orally, intestinal absorption of this vitamin can be determined with reasonable quantitative accuracy. The effect of various agents on absorption, such as intrinsic factor preparations or antibiotics, can be measured. Using a test dose of 0.5 kg. of Coso-Bi2 the average amount absorbed in eleven normal individuals was 68 per cent. In ten patients with various diseases of the small intestine 24 per cent was absorbed. In eight patients with pernicious anemia and in twelve patients who had had total gastrectomies there was essentially no absorption. Concomitant administration of intrinsic factor with the test dose had no effect in normal patients nor patients with small intestine disease, but in the pernicious anemia and total gastrectomy subjects absorption became normal in each instance. The effect of aureomycin@ or achromycin@ on the absorption of vitamin Bi2 was determined in six patients with pernicious anemia, in four patients who had had total gastrectomies and in ten patients with small intestine disease. Two tests were performed in each patient during the administration of two grams of the antibiotic daily. There was no effect on absorption in any of the patients with pernicious anemia, nor in any of the total gastrectomy group. Three of the patients with small intestine disease had megaloblastic anemia associated with intestinal anastomoses and stasis of intestinal contents. In these patients a very significant increase in absorption of Coeo-Bis occurred. Of the other seven patients two had non-tropical sprue, four had regional enteritis and one had steatorrhea due to pancreatic insufficiency. Although absorption of Bi2 was impaired in each of these seven, antibiotic administration did not result in increased absorption. The relationship of antibiotics to vitamin Blz utilization and to hematopoiesis will be discussed in the light of these findings. SERUM TRANSAMINASELEVELS IN MYOCARDIAL INFARCTION. Clarence M. Agress,* Albert A. Kattus and John S. La Due. Cardiovascular and Cardiology Lab., Gen. Medical Research
Service, V. A. Center; the Dept. of Medicine, Univ. California Medical Center, Los Angeles, Calif., and the Sloan Kettering Inst. Dept. Medicine, Memorial Center, New York, N. Y. Clinical studies by one of the authors (La Due) have shown that the serum level of transaminase rises significantly following acute myocardial infarction. This work indicated that a study of this kind in dogs, where varied amounts of infarction could be produced and more accurately followed, would prove valuable. The coronary arteries of thirteen closed-chest dogs were embolized with plastic microspheres. Twelve-lead electrocardiograms were used to follow the course of the infections and color photographs were taken of the hearts at autopsy. Serum samples were taken every four hours for the first twenty-four to thirty-six hours and some dogs were followed for seventy-two hours. The results showed that in all cases the serum transaminase level rose sharply after myocardial infarction, reaching a peak between twelve to eighteen hours after embolization. There was a relatively linear correlation between the peak serum transaminase level and the amount of myocardial infarction as estimated at autopsy. A clinical study is being carried out at the Veterans Administration Center, Los Angeles; thus far 197 determinations have been made in sixty-four patients. Eleven were controls in which the highest level was twenty-four transaminase units. A miscellaneous group, including congestive heart failure, cerebrovascular accidents, old infarcts in five patients and pericarditis in four patients were in the normal range. Peak values of thirteen patients with acute myocardial infarction ranged from 40 to 580 transaminase units. In coronary insufficiency patients, as differentiated from myocardial infarction patients, serum transaminase levels were useful in fourteen of seventeen cases. IKFLUENCEOF BLOOD TRANSFUSIONS UPON THE CIRCULATING PLATELETS IN ARTERIAL AND VENOUS BLOOD OF MAN. H. R. Bierman,* Keith H. Kelly, and Fauno L. Cordes. Hosp. Tumors and Allied Diseases, Div. Research, City of Hope Medical Center, Duarte, Calif. It has been shown by Harrington et al. that the blood or plasma of patients with idiopathic thrombocytopenic purpura (ITP) infused into volunteers will cause a thrombocytopenia in the venous blood. Prompt fall in the venous platelet level within fifteen to thirty minutes after the AMERICAN
JOURNAL
OF
MEDICINE