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DOE Openness: Human Radiation Experiments: Roadmap to the Project Experiments List |
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Experiments List
Foreword Criteria for Listing Experiments Basic Categories of Human Radiation Experiments The Process of Identifying Experiments |
University of Chicago - Argonne Cancer Research HospitalUC-1. Chromium-51 and Iron-59 Used to Study Red Blood-Cell Production STUDIES WERE CARRIED OUT in the early 1950s at the Argonne Cancer Research Hospital to determine the rate of red cell production and destruction in healthy and anemic subjects. Two to 4 microcuries of iron59 (Fe59) were added to 20 milliliters of plasma and injected into the arms of the subjects. Several days after the administration of the Fe59, the procedure was repeated using chromium51 (Cr51)Blabeled plasma. The subjects were six healthy individuals and two anemic individuals. The combined use of Cr51 and Fe59 provided an indicator of red cell survival and total blood volume in humans. This work was carried out under a contract between the Office of the Surgeon General, the United States Army, and the Department of Medicine of the University of Chicago. The U.S. Atomic Energy Commission provided funding to the Argonne Cancer Research Hospital through the University of Chicago, its operating contractor. (Included in The DOE Roadmap of February 1995) References Weinstein, I.M., and E. Beutler. AThe Use of Cr51 and Fe59 in a Combined Procedure to Study Erythrocyte Production and Destruction in Normal Human Subjects and in Patients with Hemolytic or Aplastic Anemia.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 1, Parts 1B6, 1954 to 1956. Chicago: Argonne Cancer Research Hospital, pp. 70B75. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-2. Studies on the Clinical Application of Yttrium-90 IN 1953, AT THE ARGONNE Cancer Research Hospital, preliminary studies were carried out with yttrium90 (Y90) to determine whether Y90 might be used for intracavitary therapy. A patient in the terminal stage of carcinomatosis was injected intrapleurally with a solution containing about 1.35 millicuries of Y90. Samples of fluid were drawn from the pleural cavity at 3, 24, and 48 hours and at autopsy, which was 7 days after the administration of Y90. The study found that Y90 had a biological retention halftime of 30 to 36 hours. The U.S. Atomic Energy Commission provided funding to the Argonne Cancer Research Hospital through the University of Chicago, its operating contractor. (Included in The DOE Roadmap of February 1995) References LeRoy, G.V., R.W. Wissler, and D.W. Talmage. APreliminary Studies on the Clinical Application of Yttrium90 for Intrapleural Therapy.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 1, Parts 1B6, 1954 to 1956. Chicago: Argonne Cancer Research Hospital, pp. 1B4. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-3. Chromium-51 Used to Study Primaquine Sensitivity IN 1953, THE UNIVERSITY of Chicago and the Argonne Cancer Research Hospital conducted studies to determine the hemolytic defect that develops during primaquine administration. Primaquine is an antimalarial drug that induces an acute hemolytic anemia in some people, mainly members of heavily pigmented races. The subjects for this study were healthy, male inmates from the Illinois State Penitentiary at Statesville. None of the inmates had ever had malaria. All of the primaquinesensitive subjects were AfricanAmericans and the primaquinenonsensitive subjects included both AfricanAmerican and Caucasian subjects. There was also one subject who was a student at the University of Chicago, who was included in the study because he had been splenectomized 2 years prior to the initiation of this research. Blood labeled with 200 to 300 microcuries of chromium-51 as sodium chromate was injected into both the normal subjects and the group of primaquinesensitive subjects. Subsequently, primaquine was administered to subjects in both groups. Blood samples showed that the primaquinesensitive subjects developed a severe anemia, which was attributed to a unique susceptibility of their red blood cells. This study was carried out under a contract between the Department of Medicine at the University of Chicago and the Office of the Surgeon General for the United States Army. The radiochromium was obtained under an authorization from the Isotopes Division of the U.S. Atomic Energy Commission at Oak Ridge. The Argonne Cancer Research Hospital was operated by the University of Chicago, which was funded by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995) References Dern, R.J., I.M. Weinstein, D.W. Talmage, G.V. LeRoy, and A.S. Alving. AStudies on the Mechanism of Hemolysis in PrimaquineSensitive Negroes.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 1, Parts 1B6, 1954 to 1956. Chicago: Argonne Cancer Research Hospital, pp. 37B41. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-4. Chromium-51 Used to Measure Red Cell Survival Times in Subjects with Liver Diseases IN 1953, at the Argonne Cancer Research Hospital, chromium-51 as sodium chromate was used to measure the red cell survival time of patients with liver disease. The subjects in this study were 19 patients with various types of liver disease. Liver biopsies were taken from all cases, except from four patients with bleeding tendencies. The results indicated an abnormal red cell survival time in these patients. This study was supported in part by the Office of the Surgeon General, United States Army. The Argonne Cancer Research Hospital was operated by the University of Chicago, which was funded by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995) References Jones, P.N., I.M. Weinstein, R.H. Ettinger, and R.R. Capps. ADecreased Red Cell Survival Times Associated with Liver Diseases As Measured with Radioactive Sodium Chromate.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 1, Parts 1B6, 1954 to 1956. Chicago: Argonne Cancer Research Hospital, pp. 42B46. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-5. Radioactive Carbon in Studies of Cholesterol Metabolism in Humans Using Carbon-14 IN 1955, a study on the metabolism of cholesterol was reported by the Department of Medicine and the Argonne Cancer Research Hospital of the University of Chicago and the Los Alamos Scientific Laboratory. The objective of the study was to determine the rate at which cholesterol labeled with carbon14 (C14) appeared in the plasma and to determine how much of the C14 was incorporated. This study was conducted on patients admitted to the research wards of the Argonne Cancer Research Hospital. Thirtyfour subjects with various forms of cancer were studied. Both male and female subjects were included; their ages ranged from 23 to 71 years. Patients received 100 or 200 microcuries of C14labeled sodium acetate. The C14-labeled acetate was administered either orally or intravenously, and in some cases by both routes. Larger amounts were given to patients having the shortest life expectancies. Blood was drawn from 30 minutes to several weeks after administering the C14 acetate. Some patients were subjected to additional tests to determine the amount of C14 lost from the body by respiration or excretion. This study was funded by the U.S. Atomic Energy Commission, the Damon Runyon Memorial Fund, and the American Cancer Society. (Previously described in #23 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995) References Gould, R.G., G.V. LeRoy, G.T. Okita, J.J. Kabara, P. Keegan, and D.M. Bergenstal. AThe Use of C14Labeled Acetate to Study Cholesterol Metabolism in Man.@The Journal of Laboratory and Clinical Medicine. Vol. 46, No. 3, September 1955, pp. 372B384. " UC-6. Study of the Origin of Steroid Hormones Using Tritium and Carbon-14B Labeled Compounds IN 1955, a study was conducted at the Argonne Cancer Research Hospital, in collaboration with scientists at the Los Alamos Scientific Laboratory, to determine the relationship between dietary cholesterol and the synthesis of hormones in the body. Seven patients who were to have their adrenal glands surgically removed or who were scheduled to have a therapeutic abortion, were fed 50 microcuries of tritiumlabeled (H3) cholesterol 7 days prior to surgery. An additional amount of 10 microcuries of H3labeled cholesterol was administered orally each succeeding day before surgery. During the surgery the patient was given 100 microcuries of acetate labeled with carbon14 (C14) by intravenous injection. The aborted fetuses, the removed adrenal gland, and other biopsy tissue samples were analyzed for C14 and H3labeled cholesterol and steroidbased hormones. This study showed that dietary cholesterol was rapidly converted to steroid hormones and that C14 from the acetate source was also incorporated into hormones. The research was supported by the U.S. Atomic Energy Commission. (Previously described in #23 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995) References Langham, W.H., and J.B. Storer. Biomedical Research Group of the Health Division Annual Report 1954. Los Alamos, NM: Los Alamos Scientific Laboratory, LA1889, 1955, pp. 24B25. " UC-7. Chromium-51 Used to Study Red Blood Cells THIS RESEARCH was carried out at the Argonne Cancer Research Hospital in the mid 1950s. This study was the first to use the chromium51 (Cr51) labeling technique to study red cell survival in patients with abnormal hemoglobin syndrome. The subjects were 11 black patients with various blood disorders including 4 with sickle cell anemia, as well as 2 healthy subjects. One hundred milliliters of blood were drawn from each patient, labeled with 200 microcuries of Cr51, and reinjected. Samples of blood and feces were collected and analyzed to determine red cell survival times. The study showed that there was a decreased survival of erythrocytes (red blood cells) in patients with sickle cell anemia. The U.S. Atomic Energy Commission provided funding to the Argonne Cancer Research Hospital through the University of Chicago, its operating contractor. (Included in The DOE Roadmap of February 1995, and since revised) References Weinstein, I.M., C.L. Spurling, H. Klein, and T.F. Necheles. ARadioactive Sodium Chromate for the Study of Survival of Red Blood Cells III. The Abnormal Hemoglobin Syndromes.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 1, Parts 1B6, 1954 to 1956. Chicago: Argonne Cancer Research Hospital, pp. 47B53. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-8. Digitoxin Metabolism Studies with Carbon-14 Digitoxin IN THE MID-1950s, studies were conducted at the Argonne Cancer Research Hospital on the uptake and retention of digitoxin labeled with carbon14 (C14). Digitoxin is a drug used in the treatment of cardiac failure. This study sought to determine the rate of disappearance of unchanged digitoxin and to determine the conversion products arising from the parent drug. Eight subjects with congestive heart failure were given an intravenous injection of 0.5 to 1.5 milligrams of digitoxin containing 0.36 to 0.65 microcurie per milligram of C14. Digitalis medication had been withheld from 14 to 34 days prior to the injection and none was given after the injection. Subsequent to the injection, several 10 to 20 milliliter blood samples were drawn in a 96hour period. The same researchers conducted another study, using three terminal patients. The purpose of the second study was to determine the distribution of digitoxin in various tissues of the body and to determine the pathway by which the drug is removed from the body. The radioactive digitoxin was isolated from digitalis plants that had been grown in an atmosphere of C14. The specific activity of the C14 ranged from 0.48 to 0.65 microcurie per milligram digitoxin. For three terminal patients, multiple doses were intravenously administered to maintain an adequate concentration in the tissues. Tissue samples were taken after the patients died. These tissues were analyzed for digitoxin content. Further research was conducted where radioactive metabolites of digitoxin were studied following the administration of single intravenous doses of digitoxin labeled with C14 or with H3. This research determined the reactions that digitoxin undergoes in humans. The Argonne Cancer Research Hospital was operated by the University of Chicago, which was funded by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995 and since revised.) References Okita, G.T., P.J. Talso, J.H. Curry, F.D. Smith, and E.M.K. Geiling. AMetabolic Fate of Radioactive Digitoxin in Human Subjects.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 1, Parts 1B6, 1954 to 1956. Chicago: Argonne Cancer Research Hospital, pp. 62B68. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. Okita, G.T., P.J. Talso, J.H. Curry, F.D. Smith, and E.M.K. Geiling. ABlood Level Studies of C14Digitoxin in Human Subjects with Cardiac Failure.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 1, Parts 1B6, 1954 to 1956. Chicago: Argonne Cancer Research Hospital, pp. 69B73. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. Okita, G.T., and J.H. Curry. AMetabolism of Radioactive Digitoxin in Man.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 3, Part 101, 1961 and Parts 11 to 15, 1959 to 1961. Chicago: Argonne Cancer Research Hospital, p. 101. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-9. Carbon-14B Labeled Proteins in Multiple Myeloma THIS RESEARCH WAS CARRIED OUT at the Argonne Cancer Research Hospital in the early to mid-1950s. A total of 5.41 grams of carbon14 (C14)Blabeled glycine were given orally in divided doses over an 11hour period to a patient suffering from multiple myeloma, a malignant neoplasm that originates in the bone marrow and is characterized by abnormalities in formation of plasma protein. The myeloma cells produce abnormal proteins in the serum and urine. Blood samples were drawn and 24hour urine collections were analyzed to determine the rate of synthesis and the possible precursor relationships of myeloma globulins and BenceJones proteins. In a second experiment, the same researchers conducted further experiments with another patient who had different pathological proteins and graver clinical conditions. The subject of this experiment was a 70yearold male with multiple myeloma. The patient was given 20 grams of stable nitrogen15Blabeled glycine. The results showed the direct interaction of the Bence Jones proteins with the metabolic pool of nitrogen. In a third experiment, a 64yearold female patient was injected with C14labeled L-lysine to determine the rate of synthesis and excretion of the BenceJones protein. On the day of the experiment, a catheter was inserted and the patient was injected with 300 microcuries of Llysine labeled with C14. Urine and respiration were analyzed and two dialysis experiments were performed on the patient. In a fourth experiment, a 67yearold male patient at the Argonne Cancer Research Hospital, was injected with 450 microcuries of C14 glutamic acid. One reason for conducting this last experiment was to learn whether glutamic acid might be a better compound to use to study protein synthesis than L-lysine or glycine. This research was supported by grants from the National Cancer Institute, the National Institutes of Health, and the American Cancer Society. The Argonne Cancer Research Hospital was operated by the University of Chicago, which was funded by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995) References Hardy, S., and F.W. Putnam. AProteins in Multiple Myeloma IV. Interaction with Metabolic Nitrogen.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 1, Parts 1B6, 1954 to 1956. Chicago: Argonne Cancer Research Hospital, pp. 77B80. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. Putnam, F.W., and Hardy, S. AProteins in Multiple Myeloma III. Origin of BenceJones Protein.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 1, Parts 1B6, 1954 to 1956. Chicago: Argonne Cancer Research Hospital, pp. 74B76. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. Putnam, F.W., F. Meyer, and A. Miyake. AProteins in Multiple Myeloma V. Synthesis and Excretion of BenceJones Protein.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 1, Parts 1B6, 1954 to 1956. Chicago: Argonne Cancer Research Hospital, pp. 31B37. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. Putnam, F.W., and A. Miyake. AProteins in Multiple Myeloma. VIII. Biosynthesis of Abnormal Proteins.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 2, Part 100, 1956 and Parts 7B10, 1957 to 1958. Chicago: Argonne Cancer Research Hospital, p. 27. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. Putnam, F.W., A. Miyake, and F. Meyer. AThe Metabolism of DLGlutamic Acid1C14 in Man.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 2, Part 100, 1956 and Parts 7B10, 1957 to 1958. Chicago: Argonne Cancer Research Hospital, pp. 35B43. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-10. Carbon-14B Labeled Digitoxin Administered to Pregnant Women to Determine Fetal Distribution THIS STUDY WAS CONDUCTED at the Argonne Cancer Research Hospital in the mid1950s. The purpose of the study was to investigate the transfer of digitoxin across the placental barrier of pregnant women and to determine the relative concentration of the unchanged drug and its metabolic products in various fetal organs. The subjects were four pregnant women who were hospitalized at the Chicago LyingIn Hospital. Three of the women had abortions; the fourth delivered an anencephalic baby. Three to 5 hours before hysterotomy, three of the women were intravenously given from 0.25 to 0.5 milligram of digitoxin labeled with carbon14 (C14) at a concentration of 0.25 to 0.5 microcurie per milligram. The fourth woman was given 0.5 milligram of the radioactive drug 2 to 3 hours before the expected time of delivery. The Argonne Cancer Research Hospital was operated by the University of Chicago, which was funded by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995) References Okita, G.T., E.J. Plotz, and M.E. Davis. APlacental Transfer of Radioactive Digitoxin in Pregnant Women and its Fetal Distribution.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 1, Parts 1B6, 1954 to 1956. Chicago: Argonne Cancer Research Hospital, pp. 26B30. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-11. Human Tracer Studies Using Tritium- and Carbon-14BLabeled Cholesterol IN 1957, an experiment was conducted at the Argonne Cancer Research Hospital using radioactively labeled cholesterol. A 60yearold man with chronic arthritis was the subject of this study. The subject received an intravenous injection containing 33.8 microcuries of tritiumlabeled (H3) cholesterol and 4.3 microcuries of cholesterol labeled with carbon14 (C14). Blood samples were drawn at various times, starting about 4 hours after injection and continuing periodically for 10 days. Urine samples were also collected and analyzed for C14 and H3labeled cholesterol and steroid hormones. This experiment showed the advantages of using H3 and C14 as tracers for cholesterol metabolism studies in humans. It also showed the distribution of C14 and H3 in hormones synthesized from cholesterol. This study was funded by the Damon Runyon Memorial Fund and the U.S. Atomic Energy Commission. (Previously described in #23 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995) References Werbin, H., D.M. Bergenstal, R.G. Gould, and G.V. LeRoy. AEvaluation of Tritium Cholesterol as a Tracer in Man.@The Journal of Clinical Endocrinology and Metabolism. Vol. 17, No. 3, March 1957, pp. 337B345. " UC-12. Study of Hormone Conversion During Human Pregnancy Using Carbon-14 THIS STUDY WAS CONDUCTED by the Argonne Cancer Research Hospital in the mid to late 1950s. The purpose of the study was to determine whether acetate and cholesterol are precursors of estrone in pregnant women. The subject was a 36yearold white woman who underwent a thyroidectomy prior to pregnancy. An intramuscular injection of 35.09 microcuries of testosterone4C14 was administered during the 7th week of pregnancy and an abortion was performed 4 days after the injection. About 55 percent of the radioactivity derived from the labeled testosterone was eliminated from the body by way of the kidney. The results of this experiment demonstrated the conversion of testosterone to estrone during the course of human pregnancy. The U.S. Atomic Energy Commission provided funding to the Argonne Cancer Research Hospital through the University of Chicago, its operating contractor. (Included in The DOE Roadmap of February 1995) References Ejarque, P., E.J. Plotz, and M.E. Davis. AConversion of Testosterone4C14 into EsteroneC14 During Human Pregnancy.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 2, Part 100, 1956 and Parts 7B10, 1957 to 1958. Chicago: Argonne Cancer Research Hospital, pp. 61B65. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-13. Studies on Uric Acid Labeled with Carbon-14 IN THE LATE 1950s, studies were carried out at the Argonne Cancer Research Hospital to investigate the metabolism of uric acid in humans. Uric acid labeled with carbon14 (C14) was intravenously injected into five individuals: two healthy subjects, two gouty subjects, and one patient with arteriosclerotic heart disease. Urine samples were analyzed for C14 content. For three individuals, after the administration of the C14labeled uric acid, samples of expired air were collected and radioassayed for C14-dioxide. The expired air from all three patients showed that some of the injected uric acid had been degraded to carbon dioxide and ammonia. Saliva, gastric juice, and bile were also radioassayed to determine the amount of uric acid excreted into the intestine. To verify the role of the intestinal flora on uricolysis, the degradation of intravenously administered uric acid C14 was studied before and after a high degree of intestinal bacteriostasis had developed. The subject was a healthy 57yearold male who was kept on a diet during the study and for 10 days prior to the study. After intravenous administration of 33 milligrams of uric acid containing 35 microcuries of C14, urine and expiredair samples were collected for 10 days. On the 11th day, three types of antibiotics were orally administered and after establishing the desired bacteria level in the intestinal tract, 35 microcuries of C14labeled uric acid were intravenously injected. This research found that intestinal flora play a prominent role in the degradation of uric acid in humans. The Argonne Cancer Research Hospital was operated by the University of Chicago and supported by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995) References Sorensen, L.B. AThe Degradation of Uric Acid in Man.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 2, Part 100, 1956 and Parts 7B10, 1957 to 1958. Chicago: Argonne Cancer Research Hospital, pp. 1B20. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. Sorensen, L.B. AStudies on Purine Metabolism: Uric Acid Metabolism.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 3, Part 101, 1961 and Parts 11B15, 1959 to 1961. Chicago: Argonne Cancer Research Hospital, pp. 96B98. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-14. Carbon-14 Study of the Carbon Dioxide Pool in Humans THIS RESEARCH WAS CONDUCTED in the late 1950s at the Argonne Cancer Research Hospital. Since many materials labeled with carbon14 (C14) are oxidized to C14O2, this research sought to determine the metabolic pool of carbon dioxide in humans. A solution of sodium carbonate-hydrogen labeled with C14 was given intravenously at a constant rate for a period of 2 to 4 hours, while the one subject breathed continuously through a betaparticle chamber. The Argonne Cancer Research Hospital was operated by the University of Chicago, which was funded by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995) References Okita, G.T., P. Meir, and G.V. LeRoy. AThe Carbon Dioxide Pool in Man.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 3, Part 101, 1961 and Parts 11B15, 1959 to 1961. Chicago: Argonne Cancer Research Hospital, pp. 19B21. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-15. Metabolism, Retention, and Excretion of Molybdenum-99 IN THE LATE 1950s, the Argonne Cancer Research Hospital conducted studies on the absorption and excretion of molybdenum, using molybdenum99 (Mo99). The studies were carried out on healthy subjects to determine the role of molybdenum in the oxidation of hypoxanthine and xanthine (precursors of uric acid). The urinary excretion rate of molybdenum in normal subjects was determined. Molybdenum was readily absorbed from the gastrointestinal tract. Seventyfive percent of ingested Mo99 was recovered in the first 24hour urine sample. The Argonne Cancer Research Hospital was operated by the University of Chicago, which was funded by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995) References Sorenson L.B. ADetermination of Molybdenum in Biological Material.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 3, Part 101, 1961 and Parts 11B15, 1959 to 1961. Chicago: Argonne Cancer Research Hospital, p. 99. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-16. Metabolism of Strontium-85 and Calcium-47 IN 1960, at the Argonne Cancer Research Hospital, tracer amounts of strontium85 (Sr85) as strontium chloride, in amounts of 26 to 40 microcuries, were administered intravenously to seven adult subjects (six males and one female). Measurements were made of Sr85 in blood specimens, urine specimens, and the total body. The subjects included a woman with moderate osteoporosis, a 66yearold male with multiple myeloma, and two males in the 60year age group. The research found that strontium is retained with greater avidity where there is deossification of the skeleton (skeletal disease). One other patient with metastatic parathyroid carcinoma was intravenously administered 50 microcuries of Sr85, and total-body counting was performed over a 238day period. Studies on the metabolism of calcium were carried out using calcium47 (Ca47). Sixteen hospitalized patients were counted in the whole-body counting facility following a single 20microcurie injection of Ca47. The Argonne Cancer Research Hospital was operated by the University of Chicago, which was funded by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995) References Hasterlik, R.J. AMetabolic Studies of Alkaline Earth Metals: Metabolism of Strontium and Calcium in the Human.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 3, Part 101, 1961 and Parts 11B15, 1959 to 1961. Chicago: Argonne Cancer Research Hospital, pp. 11B13. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. Hasterlik, R.J., G.V. LeRoy, and C.M. Newton. AThe Argonne Cancer Research Hospital Total-Body Counter.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 5, Parts 21B25, Parts 102B104, 1964 to 1966. Chicago: Argonne Cancer Research Hospital, pp. 70B72. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-17. Development of Iodine131BLabeled Fluorescein as a Brain Tumor Imaging Agent THIS STUDY WAS CONDUCTED in 1960 at the Argonne Cancer Research Hospital. Fluorescein labeled with radioiodine (I131) was developed to diagnose tumors of the central nervous system. Information obtained included the rate of disappearance from the blood, the rate of excretion, distribution in tissues, and comparison of concentrations in brain tumors and in normal brain tissue. Patients suspected of having brain tumors were selected for studies on the localization and retention of I131fluorescein. The I131-fluorescein was administered by intravenous injection. Urine and stool samples were also collected from six patients over a 48hour period for I131 analysis. Two normal volunteers were also injected with 5.7 microcuries of I131fluorescein. A total of 102 patients were involved as subjects. This research was supported in part by a grant from the American Cancer Society. The Argonne Cancer Research Hospital was operated by the University of Chicago, which was funded by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995) References Tocus, E.C., G.T. Okita, J.P. Evans, and S. Mullan. AThe Localization of OctoiodofluoresceinI131.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 3, Part 101, 1961 and Parts 11B15, 1959 to 1961.Chicago: Argonne Cancer Research Hospital, pp. 104B113. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-18. Studies Using Carbon-14BLabeled Compounds in Patients with Gout STUDIES WERE CONDUCTED by the Argonne Cancer Research Hospital in the early 1960s on patients with gout, to determine the metabolism of uric acid in humans. This research was conducted to determine whether patients with various degrees and types of gout had an increased incorporation of glycine into uric acid. Gout is an inherited metabolic disorder characterized by chronic arthritis and usually by an elevated uricacid blood level. Twelve patients with gout were intravenously administered glycine labeled with carbon14 (C14) over a period of 60 minutes. The results of these experiments demonstrated that excessive incorporation of glycine into uric acid is usually confined to gouty subjects with abnormally high urinary outputs of uric acid. Three of the subjects who were overproducers of uric acid were studied in detail to determine the pathway whereby glycine is incorporated into uric acid more promptly than in normal humans. Two of the healthy subjects and one other patient with gout, who did not overproduce uric acid, were also part of this study. These individuals were administered azathioprine, a cytotoxic and immunosuppressive agent, for 7 to 10 days prior to the intravenous administration of 100 microcuries of glycine labeled with C14. This research found that when azathioprine was given to subjects who overproduce uric acid, their urinary uric acid fell to normal values. The Argonne Cancer Research Hospital was operated by the University of Chicago, which was funded by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995) References Sorensen L.B. AThe Pathogenesis of Gout.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 4, Parts 16B20, 1961 to 1963. Chicago: Argonne Cancer Research Hospital, pp. 23B40. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. Sorensen L.B. ASuppression of the Shunt Pathway in Primary Gout by Azathioprine.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 5, Parts 21B25, Parts 102B104, 1964 to 1966. Chicago: Argonne Cancer Research Hospital, pp. 56B61. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-19. Use of Molybdenum-99 for Liver Scanning Studies THE EARLY 1960S, the Argonne Cancer Research Hospital used molybdenum99 (Mo99) as a tracer agent to image the liver and to determine the disappearance from the blood of intravenously injected Mo99. Both normal subjects and patients with liver disease were administered between 40 and 100 microcuries of Mo99 by intravenous injection. Liver scans were performed at the Argonne Cancer Research Hospital=s whole-body counting facility. Subjects included normal volunteers and one patient with viral hepatitis. Approximately 100 liver scans were performed using Mo99 as a tracer. The Argonne Cancer Research Hospital was operated under contract by the University of Chicago, which was funded by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995) References Sorensen, L.B., and M. Archambault. AVisualization of the Liver by Scanning Using Mo99 (Molybdate) as Tracer.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 4, Parts 16B20, 1961 to 1963. Chicago: Argonne Cancer Research Hospital, pp. 57B68. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. Sorensen, L.B. and M. Archambault. AVisualization of the Liver by Scanning with Mo-99 (Molybdate) as Tracer.@The Journal of Laboratory and Clinical Medicine, Vol, 62, No. 2, JulyBDecember 1963, pp. 330B340. " UC-20. Metabolism of Lithocholic Acid Labeled with Carbon-14 THESE STUDIES WERE carried out by the Argonne Cancer Research Hospital in the early 1960s to determine the metabolism of lithocholic acid. Lithocholic acid, a steroid produced by the human body, is found in human bile and feces. A dose of 11 microcuries of lithocholic acid labeled with carbon14 (C14) was orally administered to four patients, 20 to 72 hours before they underwent elective gallbladder surgery for gallstones. Two other patients with functioning gallbladders were studied after oral administration of 50 microcuries of lithocholic acid labeled with C14. Bile was obtained during their gallbladder operations and analyzed for C14. The Argonne Cancer Research Hospital was operated under contract by the University of Chicago, which was funded by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995) References Norman, A., and R.H. Palmer. AMetabolites of Lithocholic Acid24C14 in Human Bile and Feces.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 5, Parts 21B25, Part 102B104, 1964 to 1966.Chicago: Argonne Cancer Research Hospital, pp. 65B81. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. Palmer, R.H. AThe Formation of Bile Acid Sulfates: A New Pathway of Bile Acid Metabolism in Humans.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 6, Parts 26B33.Chicago: Argonne Cancer Research Hospital, pp. 71B75. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-21. Preliminary Tracer Studies Using Technetium-99m and Iodine-131 STUDIES WERE CONDUCTED in 1961 at the Argonne Cancer Research Hospital on the use of technetium99m (Tc99m) as a tracer and imaging agent for nuclear medicine. The purpose of this research was to determine the biological retention halftime, and suitability as an imaging agent, of Tc99m. Scans of subjects were made with a Picker Magnascanner 30 minutes after intravenous injection of Tc99m. Overall, 86 patients were studied. Fifty-seven had normal thyroid function, 17 had overactive thyroids, 6 had underactive thyroids, and 6 had no thyroid function. One white female received an intravenous injection of 1 millicurie of Tc99m. Thyroid scans were conducted on a clinically normal white male, 30 minutes after intravenous injection of Tc99m, and the results were compared with scans conducted after iodine131 (I131) administration. The urinary and fecal excretion of Tc99m pertechnetate was studied in four patients. At least two normal subjects, including a healthy AfricanAmerican male, were administered 440 microcuries of Tc99m. Another male subject was administered 1 millicurie of Tc99m and dose calculations were made for the total body, stomach, and thyroid. With a biological retention halftime of 48 hours, Tc99m was found to be a suitable imaging agent. It provided good scans with unmodified equipment, while providing a radiation dose to the thyroid of only 100 millirads, or one-thousandth of the dose from 50 microcuries of I131. The Argonne Cancer Research Hospital was operated under contract by the University of Chicago, which was funded by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995, and since revised.) References Andros, George, P.V. Harper, K.A. Lathrop, and R.J. McCardle. APertechnetate-Tc99m Localization in Man with Applications to Thyroid Scanning and the Study of Thyroid Physiology.@The Journal of Clinical Endocrinology and Metabolism. Vol. 25, No. 8, August 1965, pp. 1,067B1,076. Harper P.V., G. Andros, and K. Lathrop. APreliminary Observations on the Use of 6Hour Tc99m as a Tracer in Biology and Medicine.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 4, Parts 16B20, 1961 to 1963. Chicago: Argonne Cancer Research Hospital, pp. 76B88. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. Harper P.V., and K. Lathrop. ATechnetium99m as a Scanning Agent.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 5, Parts 21B25, Part 102B104, 1964 to 1966.Chicago: Argonne Cancer Research Hospital, pp. 96B98. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. Harper P.V., and K. Lathrop. AThe Pharmacodynamics of Technetium Pertechnetate (Tc99m O4).@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 5, Parts 21B25, Parts 102B104, 1964 to 1966.Chicago: Argonne Cancer Research Hospital, pp. 97B98. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. Harper P.V., K.A. Lathrop, R.J. McCardle, and G. Andros. AThe Use of Tc99m as Pertechnetate for Thyroid Liver and Brain Scanning.@Semiannual Reports to the U.S. Atomic Energy Commission.Vol. 5, Parts 21B25, Parts 102B104, 1964 to 1966.Chicago: Argonne Cancer Research Hospital, pp. 119B133. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-22. Metabolism and Absorption of Skin Medications Labeled with Carbon-14 THIS RESEARCH WAS CONDUCTED by the Argonne Cancer Research Hospital in the mid-1960s. Eleven normal and nine psoriatic Caucasian volunteers served as subjects. Palmitic acid containing 1 microcurie of carboxyl carbon (C14) label dissolved in petroleum ether was dripped onto each of two demarcated areas of lesionfree skin on the back of each subject. After 2.5 hours, the skin was wiped with petroleum ethersoaked cotton and counted for C14 activity. The entire study was repeated in four additional normal volunteers following the application of an ointment comparable to the standard treatment for psoriasis. The study was also repeated in one other normal volunteer and in two patients with minor eczema. The Argonne Cancer Research Hospital was operated under contract by the University of Chicago, which was funded by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995) References Gara, A., E. Estrada, S. Rothman, and A.L. Lorincz. ADeficient Cholesterol Esterifying Ability of LesionFree Skin Surfaces in Psoriatic Individuals.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 5, Parts 21B25, Parts 102B104, 1964 to 1966. Chicago: Argonne Cancer Research Hospital, pp. 62B69. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. Lorincz, A.L. ASpecific Metabolic Processes in Skin.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 5, Parts 21B25, Parts 102B104, 1964 to 1966. Chicago: Argonne Cancer Research Hospital, p. 75. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-23. Studies on the Use of Iodine-131 Antifibrinogen THIS WAS A COLLABORATIVE study between the Argonne Cancer Research Hospital and the University of Rochester conducted in the mid1960s. Its purpose was to determine the diagnostic and therapeutic potential of antifibrinogen labeled with iodine131 (I131), which was thought to combine with circulating fibrinogen and to localize in tumors. In half of the tumors studied, localization allowed for clear visualization on scanning. The I131-labeled antifibrinogen was intravenously administered. This procedure was carried out in two patients. Although some tumors imaged, this study was not successful in treating cancer because of poor tumor localization of the I131 antifibrinogen. The Argonne Cancer Research Hospital was operated under contract by the University of Chicago, which was funded by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995) References Harper, P.V., and I. Spar. AI131Antifibrinogen.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 5, Parts 21B25, Parts 102B104, 1964 to 1966. Chicago: Argonne Cancer Research Hospital, pp. 98B100. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-24. Bone-Tissue Radiography Using an External Source of Iodine-125 A METHOD WAS DEVELOPED at the Argonne Cancer Research Hospital in Chicago to measure bone mineral content in animals or humans, using an external iodine125 (I125) source. Bone mineral was determined by transmitting a small beam of photon radiation from an I125 source through a single human finger bone, capturing an image of the finger on radiographic film. Mineral content was determined by analyzing the image density. This technique was tested on a group of postmenopausal women (with ovaries removed) who were estrogen deficient to determine the beneficial effects of estrogen therapy on bone mineralization. Another group of postmenopausal women with ovaries and no hormone therapy was also studied, again using finger bone radiography. A group of premenopausal women served as controls. One hundred patients participated in this study. The study showed that hormone therapy had a beneficial effect on bone mineral content in women. The Argonne Cancer Research Hospital was operated by the University of Chicago and supported by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995) References Lanzl, L.H., and N.M. Strandjord. AMeasurement of Bone Mineral Content Using a Radioactive Device.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 5, Parts 21B25, Parts 102B104, 1964 to 1966. Chicago: Argonne Cancer Research Hospital, pp. 141B142. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-25. Retention of Iron-59 in the Lungs THIS STUDY WAS CONDUCTED at the Argonne Cancer Research Hospital in 1967. This study compared the amount of blood lost from the body to that retained from the lungs in a menopausal woman with pulmonary hemosiderosis, a disease characterized by expectoration of blood from the lungs or bronchial tubes. This was the first study in which linear profile scanning of iron59 (Fe59) was used for this purpose. When the patient was in remission from the disease, 10 microcuries of Fe59 were injected intravenously. Analysis was done on plasma iron clearance, serial body surface counting rates, erythrocyte incorporation, and linear profile scanning of Fe59. The Argonne Cancer Research Hospital was operated under contract by the University of Chicago, which was funded by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995) References DeGowin, R.L., L.B. Sorensen, D.B. Charleston, A. Gottschalk, and J.H. Greenwald. ARetention of Radioiron in the Lungs of a Woman with Idiopathic Pulmonary Hemosiderosis.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 6, Parts 26B33, 1966 to 1970. Chicago: Argonne Cancer Research Hospital, pp. 28B37. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " THIS RESEARCH WAS CONDUCTED by the Argonne Cancer Research Hospital in the late 1960s to determine whether induced hyperthyroidism increased the sensitivity of tumors to therapeutic xrays. The subjects of this experiment were patients with advanced cancer who could tolerate an elevated metabolic rate caused by oral doses of triiodothyronine. Xrays were also administered in daily fractionated doses. In two patients with bronchogenic carcinomas, after induction of the hyperthyroid condition, the metastases on one side were treated and the other side was treated only after the basal metabolic rate had been allowed to return to normal. At autopsy, 3 months after the treatment, the side treated with the drug and the xrays showed only fibrosis while the tumor was still present in the side treated by xrays alone. Another patient with lung metastasis due to melanoma was subjected to the combined treatment with no response. In two patients with adenocarcinoma brain metastases and unknown primary lesions, the combined therapy was effective on the brain lesions but not on the primary lesions. The U.S. Atomic Energy Commission provided funding to the Argonne Cancer Research Hospital through the University of Chicago, its operating contractor. (Included in The DOE Roadmap of February 1995, and since revised). References Griem M.L., and J.A. Stein. AThe Effect of Ltriiodothyronine on Radiation Sensitivity.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 3, Part 101, 1961 and Parts 11B15, 1959 to 1961.Chicago: Argonne Cancer Research Hospital, pp. 52B54. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-27. Metabolism and Retention Studies Using Selenium-75 THESE STUDIES WERE carried out in the late 1960s at the Argonne Cancer Research Hospital to determine the organ uptake of selenium75 (Se75). Four subjects were intravenously injected with Se75. The first was a male with a varicose ulcer who was administered 100 microcuries. The second was a male with mild diabetes who was administered 200 microcuries on one occasion and was subsequently administered 220 microcuries. Subjects were followed by whole-body counting for up to 30 months. The biological halftime was found to be about 80 days. The results of this study found that after a single injection of Se75, onehalf of the Se75 was eliminated from the body after 80 days. The Argonne Cancer Research Hospital was operated under contract by the University of Chicago, which was funded by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995) References Lathrop, K.A., P.V. Harper, and F.D. Malkinson. AHuman Total-Body Retention and Excretory Routes of Se75 from Selenomethionine.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 6, Parts 26B33, 1966 to 1970. Chicago: Argonne Cancer Research Hospital, pp. 49B57. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-28. Comparison of Gallium-68, Technetium-99m, and Indium113m for Diagnosis of Tumors IN THE LATE 1960s, the Argonne Cancer Research Hospital conducted studies to determine the combination of radionuclide preparation and imaging system with the best lesiondetection capabilities per unit radiation dose. Preparations of gallium68 (Ga68), technetium99m (Tc99m), and indium113m (In113m) were used to detect lesions in the brain, kidney, liver, and lung. Biological halftimes in humans were compared with those in mice by measuring radioactivity in the excreta. The Argonne Cancer Research Hospital was operated under contract by the University of Chicago, which was funded by the U.S. Atomic Energy Commission.(Included in The DOE Roadmap of February 1995) References Lathrop, K.A., T.D. Cohen, R.N. Beck, and P.V. Harper. AComparison of Gallium68, Technetium99m, and Indium113m Used with the Gamma Camera and the 3Inch and 5Inch Scanners for Visualization of Lesions in the Brain, Kidney, Liver, and Lung.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 6, Parts 26B33, 1966 to 1970. Chicago: Argonne Cancer Research Hospital, pp. 1B13. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-29. Study of X-Ray Treatment of Gastric Ulcers FROM 1937 TO 1954, researchers at the University of Chicago Department of Medicine conducted studies of the treatment of gastric (stomach) ulcers using radiation from xrays. The purpose of the study was to evaluate the therapeutic benefits of xrays in treating gastric ulcers. The subjects were 116 patients with gastric ulcers; they ranged in age up to 70 years. All received xray therapy in addition to other therapy. The goal of the xray therapy was to reduce acid gastric secretions and to facilitate ulcer healing. The estimated total dose to stomach tissues ranged from 1,100 to 2,930 rads. The researchers claimed that moderate irradiation of the stomach reduced acid secretion and served as a safe and valuable adjunct to conventional treatment of benign gastric ulcers. However, this form of therapy was discontinued as the risks were perceived to outweigh the benefits, and as nonradiation remedies for treating gastric ulcers were developed. Similar studies were conducted from 1936 to 1947 involving about 800 patients in an effort to reduce stomach acid secretions and allow healing of gastric ulcers. This work was supported by the U.S. Atomic Energy Commission. References Levin, E., A. Hamann, and W.L. Palmer. AThe Effect of Radiation Therapy on the Nocturnal Gastric Secretion in Patients with Duodenal Ulcer.@Gastroenterology. Vol. 8, No. 5, May 1947, pp. 565B574. Levin, E., J.B. Kirsner, and W.L. Palmer. AGastric Ulcers in the Aged.@Geriatrics. Vol. 4, No. 1, JanuaryBFebruary 1949, pp. 362B373. Levin, E., W.L. Palmer, and J.B. Kirsner. AObservations on the Diagnosis, Treatment, and Course of Gastric Ulcer.@Journal of the American Medical Association. Vol. 156, No. 15, December 1954, pp. 1,383B1,389. Ricketts, W., J.B. Kirsner, E.M. Humphreys, and W.L. Palmer. AEffect of Roentgen Irradiation on the Gastric Mucosa.@Gastroenterology. Vol. 11, No. 6, December 1948, pp. 818B832. Ricketts, W., W.L. Palmer, J.B. Kirsner, and A. Hamann. ARadiation Therapy in Peptic Ulcer: An Analysis of Results.@Gastroenterology. Vol. 11, No. 6, December 1948, pp. 789B806. " UC-30. Experimental Neurosurgery Using Palladium-109 and Silver-111 Implants in Parkinson=s Disease Patients IN THE 1950s, it was common for neurosurgeons to try to control the abnormal movements and rigidity of Parkinson=s disease by creating cerebral lesions. The surgical methods then in use all had some type of disadvantage. Researchers at the Division of Neurological Surgery, Department of Radiology and at the Argonne Cancer Research Hospital collaboratively investigated the use of beta-ray source implants as an alternative method for creating similar lesions. Eight patients with Parkinson=s disease were treated using palladium-109 (Pd109) to induce the desired lesions. A Pd109 needle was inserted through the skull under local anesthetic, using intensified fluoroscopic mapping to monitor the insertion and placement of the needle. Most patients had alleviation of rigidity or tremor or both upon placement of the needle. In others, the improvement progressed while the needle remained in place for up to 90 minutes. If the Parkinson=s disease symptoms returned, the procedure was repeated and another lesion was made. The radiation dose to the patient=s skin during the fluoroscopic monitoring was estimated to be equivalent to a fluoroscopic examination of the gastrointestinal tract. The researchers also investigated the use of silver-111 as an alternative, implanted bilaterally in two Parkinson=s disease patients. This study showed that the radiation implants produced satisfactory relief of symptoms in the patients treated. This work was supported by the Simms Foundation. The Argonne Cancer Research Hospital was operated by the University of Chicago, under contract with the U.S. Atomic Energy Commission. References Mullan, S., R.D. Moseley, Jr., and P.V. Harper, Jr. AThe Creation of Deep Cerebral Lesions By Small Beta-Ray Sources Implanted Under Guidance of Fluoroscopic Image Intensifiers (As Used in the Treatment of Parkinson=s Disease).@American Journal of Roentgenology, Radiation Therapy, and Nuclear Medicine. Vol. 82, No. 4, October 1959, pp. 613B617. Mullan, S., R.D. Moseley, Jr., and P.V. Harper, Jr. AThe Creation of Deep Cerebral Lesions By Small Beta-Ray Sources Implanted Under Guidance of Fluoroscopic Image Intensifiers (As Used in the Treatment of Parkinson=s Disease).@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 3, Part 101, 1961. Chicago: Argonne Cancer Research Hospital, pp. 33B38. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " BY THE EARLY 1950s, it was thought that inactivation of the pituitary gland might be effective for the long-term control of metastatic neoplasms of certain hormonally influenced tissues such as those in the breast and prostate. Some studies had shown that surgical removal of the pituitary gland had no significant effect on the tumors, and that residual pituitary tissue identified in these cases at autopsy was thought to have accounted for this lack of effect. Further research conducted at Argonne Cancer Research Hospital sought to determine whether total destruction of the pituitary gland could be accomplished by irradiation using yttrium-90 (Y90) pellets implanted into the gland. In 1954, following completion of preliminary animal experiments, pituitary gland irradiation was initiated in a series of patients with advanced metastatic cancers of hormonally influenced tissues with some hope of achieving a palliative effect. Initially, four pellets of Y90 containing 0.63 to 0.88 millicurie per Y90 pellet were inserted into the bony sella of the skull in each of six patients. One of these patients later had two additional pellets implanted. On the basis of autopsy findings, it was determined that the radiation dose from four pellets was inadequate for total destruction of the pituitary, and that proper placement of the pellets in the pituitary was technically more difficult than had been anticipated. The protocol was modified and three additional patients were each implanted with six Y90 pellets. Subsequently, another eight patients were implanted with seven or eight pellets each that had an average total activity of 6 millicuries. In five of the later cases, the implantation procedure was performed under local rather than general anaesthesia because of the patients=poor preoperative condition. At least one patient experienced some palliative benefit following the treatment with Y90 pellets. This study showed that irradiation of the pituitary gland using Y90 pellets was less risky to the patient than surgical excision. This research was supported by the U.S. Atomic Energy Commission. References Harper, P.V., R.D. Moseley, Jr., W.S. Ironside, W.A. Kelly, W. Fenge, and W. De Vos. AExperiences with Yttrium-90 Hypophysectomy.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 2, Part 9, 1958. Chicago: Argonne Cancer Research Hospital, pp. 1B20. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. Rasmussen, T.B., P.V. Harper, E. Yuhl, and D.M. Bergenstal. AThe Destruction of the Pituitary Gland in Metastatic Cancer with Yttrium-90 Pellets.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 1, Part 3, 1955. Chicago: Argonne Cancer Research Hospital, pp. 1B16. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-32. Treatment of Pancreatic Cancer Using Implanted Iodine-131 IN THE EARLY 1950s, an established cancer treatment was adapted for use at the Argonne Cancer Research Hospital in patients with carcinoma of the pancreas. This procedure was used to treat carcinoma of the pancreas in seven patients. The subjects ranged in age from 42 to 66 years. In this procedure, fine polyethylene tubing filled with mercury was threaded through and around patients=abdominal tumors. The placement of the tubing was checked by x-ray imaging before closing the abdomen. Further x-ray images of the implant with stable mercury in the tubing were made, and from these, the volume of tissue to be irradiated was calculated. Subsequently, the contents of a centrifuge tube containing an isotope solution of iodine-131 (I131) were drawn by suction into the tubing. Vulnerable organs were surgically moved a small distance away from the tubing. The amounts of I131 placed in the tubing ranged from 28 to 176 millicuries, and the calculated total radiation dose to the tumors ranged from 5,000 to 9,200 rads. This method of treatment provided palliative (relief, not cure) benefit for four patients and appeared to extend the survival of one patient. The results indicated radiation could be delivered to intra-abdominal tumors in greater amounts than could be tolerated using external-beam radiation therapy, with less irradiation of normal tissues. The Argonne Cancer Research Hospital was operated by the University of Chicago, under contract with the U.S. Atomic Energy Commission. References Harper, P.V., and K.A. Lathrop. AIsotope Therapy for Intra-Abdominal Tumors.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 1, Part 2, 1954. Chicago: Argonne Cancer Research Hospital, pp. 54B61. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-33. Chicago Studies of the Metabolism of a Tuberculosis Drug Using Carbon-14 IN 1952, the University of Chicago conducted studies on the distribution and excretion of isoniazid, a new and clinically accepted antituberculosis drug, using isoniazid chloride labeled with carbon-14 (C14). The study subjects were three patients being treated for tuberculosis at the University of Chicago Clinics, one male and two females, ages 23, 28, and 40 years, respectively. The subjects were administered one or two intramuscular injections of 200 to 430 microcuries of C14-labeled isoniazid chloride to determine its distribution and excretion from the body over time. Samples obtained from the subjects for C14-isoniazid analysis included surgically removed tissues, whole blood, plasma, urine, saliva, gastric juice, spinal fluid, pleural fluid, and feces. This study showed that peak levels of isoniazid in blood and plasma were reached within 1 hour after injection, that measurable quantities were found in blood and plasma 3 to 7 days after a single injection, and that the drug diffused freely throughout the body, with highest concentrations in the lung and skin tissues. This study contributed to the understanding of the metabolism of isoniazid, which became an important factor in the effective treatment of tuberculosis. It was supported by a grant from Motorola Inc., and by the Abbott Memorial Research Fund of the University of Chicago, the U.S. Public Health Service, and the U.S. Atomic Energy Commission. References Barclay, W.R., R.H. Ebert, G.V. LeRoy, R.W. Manthei, and L.J. Roth. ADistribution and Excretion of Radioactive Isoniazid in Tuberculosis Patients.@Journal of the American Medical Association. Vol. 51, No. 16, April 18, 1953, pp. 1,384B1,388. " UC-34. Cholesterol Studies Using Carbon14 and Tritium DURING THE MID-1950s, researchers in the Department of Medicine, University of Chicago and the Argonne Cancer Research Hospital, in collaboration with Los Alamos Scientific Laboratory conducted studies on cholesterol synthesis using carbon-14 (C14)Blabeled acetate and tritium (H3)-labeled cholesterol tracers. The purpose of this study was to develop a double isotope labeling technique for investigating the metabolism of sterols and steroid hormones in man. Specifically, this work studied the conversion of acetate to cholesterol. Four female hospital patients ranging in age from 36 to 60 years participated as subjects. Each subject was intravenously administered 100 to 200 microcuries of C14-labeled acetate and orally administered 18.2 to 70.2 microcuries of H3-labeled cholesterol. Carbon-14 activity was measured in exhaled breath as C14O2 and H3 activity was measured in cholesterol that had been isolated from blood samples. Tissue biopsies were obtained from selected organs and tissues for C14 and H3 analysis; these included the left ovary, tumor tissue (if present), right 12th rib, right adrenal, peritoneal fat, muscle, and skin. These studies verified the feasibility of the double tracer technique for investigating cholesterol metabolism in humans and showed cholesterol synthesis in the adrenals and ovaries. This work was supported by the Damon Runyon Memorial Fund, the American Cancer Society, the Chicago Lying-In Hospital, and the U.S. Atomic Energy Commission. References LeRoy, G.V., R.G. Gould, D.M. Bergenstal, H. Werbin, and J.J. Kabara. AStudies on Extrahepatic Cholesterol Synthesis and Equilibrium in Man Using a Double Labeling Technique.@The Journal of Laboratory and Clinical Medicine. Vol. 49, JanuaryBJune 1957, pp. 858B868. " UC-35. Study of Glutamic Acid Metabolism Using Carbon-14 Tracer DURING THE MID-1950s, researchers at the Argonne Cancer Research Hospital conducted studies on the metabolism of D-glutamic acid (an amino acid occurring in proteins) using carbon-14 (C14) as a tracer. D-glutamic acid metabolism had not been fully explored in humans, although this acid was thought to be present in human and animal tumors, and thus was of interest in understanding tumor development. A 67-year-old male terminal cancer patient served as the study subject. Approximately 450 microcuries of C14 DL-glutamic acid were given intravenously over a 15-minute interval to the fasting patient. Nineteen blood samples were obtained within the following 24 hours by intravenous catheter, and urine samples were collected by urethral catheter. Time curves were determined for the C14 activity of expiratory CO2 and for blood and urine components. This study showed that L-glutamic acid was metabolized rapidly, but was excreted apparently unchanged in the urine. It also was not incorporated in significant amounts into the Bence-Jones protein, thought to originate in tumor cells of multiple myeloma. Autopsy samples of tumor tissue obtained 2.5 months after administration of the labeled amino acid were devoid of detectable C14 activity. A diagnosis of multiple myeloma was confirmed at autopsy. This research was aided in part from grants from the National Cancer Institute, the National Institutes of Health, and the American Cancer Society. The Argonne Cancer Research Hospital was operated by the University of Chicago under a contract from the U.S. Atomic Energy Commission. References Putnam, F.W., A. Miyake, and F. Meyer. AThe Metabolism of DL-Glutamic Acid-1-C14 in Man.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 2, Part 10, 1958. Chicago: Argonne Cancer Research Hospital, pp. 35B43. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. Putnam, F.W., A. Miyake, and F. Meyer. AThe Metabolism of DL-Glutamic Acid-1-C14 in Man.@Journal of Biological Chemistry. Vol. 231, 1958, p. 657. " UC-36. Study of the Metabolism of Progesterone Using Carbon-14 IN THE MID-1950s, researchers in the Department of Obstetrics and Gynecology at the University of Chicago, and the Chicago Lying-In Hospital studied the metabolism of progesterone and its related compounds during the human reproductive cycle, and during pregnancy. The study groups were composed of 6 nonpregnant females, 5 subjects following interruption of pregnancy, and 11 pregnant subjects scheduled for therapeutic abortions. All subjects received a single intramuscular injection of progesterone labeled with carbon-14 (C14). Each injection contained about 25 to 30 microcuries of C14. Five subjects received a second intramuscular injection of progesterone-C14, 5 to 9 days after termination of pregnancy. Progesterone-C14 was also administered by intravenous injection to one subject during week 11 of pregnancy. Samples of plasma, urine, feces, expired air, and maternal and fetal tissue, obtained during surgical interruption of pregnancy, were collected for analysis. Proges-terone-21-C14 (28.3 to 28.8 microcuries) was administered by intravenous injection to another subject during week 11 of pregnancy. Seventeen (")-hydroxyproges-terone-4-C14-caproate (25.9 to 28.8 microcuries) was administered by intramuscular injection to four other pregnant subjects, followed by collection of urine specimens from each subject for a period of 7, 12, 14, and 15 days, respectively. Clearance, deposition, and excretion patterns were evaluated for the three compounds and their metabolites. No relationship was found between the amount of radioactivity excreted and either the stage of pregnancy or the patient=s clinical condition. There was no difference in the average urinary output of radioactivity before and after termination of early pregnancy or for the group of nonpregnant women. The work was supported by the May Cave Willet Research Fund, the Douglas Smith Foundation for Medical Research Fund, the Joseph Bolivar DeLee Memorial Fund, the University of Chicago, and the Argonne Cancer Research Hospital Fund. The Argonne Cancer Research Hospital was operated by the University of Chicago, under contract with the U.S. Atomic Energy Commission. References Davis, M.E., E.J. Plotz, C.I. Lupu, and P.M. Ejarque. AThe Metabolism of Progesterone and its Related Compounds in Human Pregnancy.@Fertility and Sterility. Vol. 11, No. 1, 1960, pp. 18B48. " UC-37. Influence of a Brain Extract on Cholesterol Metabolism Using Carbon-14 as a Tracer IN THE MID-1950s, it was discovered that an extract of mammalian brain had hypocholester-emic properties (inducing abnormally small amounts of cholesterol in the blood) in humans. Research was conducted at the Argonne Cancer Research Hospital in collaboration with the Department of Medicine, University of Chicago, in the late 1950s to determine the mechanisms by which the brain extract had effects in humans. Study subjects were three patients with coronary disease who were hospitalized in the metabolism ward. Two of these patients had an excess amount of cholesterol in their blood. All had normal basal metabolic rates and fasting blood glucose levels. After 4 to 5 days of a low-fat, low-cholesterol hospital diet, 2 milliliters of a solution of carbon-14 (C14)Blabeled sodium acetate containing 100 microcuries C14 per milliliter were injected intravenously into each subject. Blood was drawn twice in a 24-hour period and thereafter at 2- to 3-day intervals for cholesterol analysis. Two weeks after the initial injection, and 10 days after for one subject, 30 to 40 grams per day of the brain extract were administered orally to each subject for the rest of their hospitalization. After 2 weeks on this material, two of the subjects were again injected with 200 microcuries of C14-labeled sodium acetate. The research established that the brain extract acts by partially binding the intestinal cholesterol and its end products to enhance their excretion. This study was supported by grants from the American Heart Association and the U.S. Public Health Service. The Argonne Cancer Research Hospital was operated by the University of Chicago, under contract with the U.S. Atomic Energy Commission. References Jones, R.J., O.K. Reiss, and M.F. Golden. Influence of a Brain Extract Upon Cholesterol Metabolism. Chicago: Argonne Cancer Research Hospital, pp. 212B220. The University of Chicago, Office of Legal Counsel, Reprints of the Argonne Cancer Research Hospital, Vol. III, 1961. " UC-38. Experimental Cancer Therapy Using Permanent Chromium-51 Implants IN 1959, RESEARCHERS in the Departments of Radiology and Surgery at the University of Chicago and the Argonne Cancer Research Hospital, began a collaborative investigation of the use of implanted chromium-51 (Cr51) gamma ray sources for interstitial (within tumor tissue) radiation therapy for cancer. The implants consisted of Cr51 wire in aluminum tubes, which were implanted within regions of tissue containing cancer cells. The first cancer patient was treated in 1959 for metastatic squamous cell cancer of the anus. The next patient was not treated until approximately 1964 and, over a 2-year period, the researchers performed a total of 30 additional implants to treat 24 patients who had a variety of advanced cancers. Most of these patients had received previous external radiation and radium therapy, with or without surgery. Between 3 and 60 Cr51 seeds, each ranging in activity from 2 to 5 millicuries, were implanted through the skin into the tumor tissue in each patient. Five patients had multiple implants, up to a maximum of three in one patient. Favorable responses were obtained in nine patients, including the first treated, who experienced no symptoms or cancer recurrence during the 7.5 years of follow-up. Seven others had good responses. Of the five remaining patients, four had questionable or unfavorable results and for one patient, follow-up was too short for adequate evaluation. Tissue destruction and hemorrhages occurred in three patients, all of whom had received radiation therapy prior to the implantation. Permanent Cr51 implants were generally well tolerated by the other previously irradiated patients. This work was supported in part by a Cancer Development Award from the National Institutes of Health. The Argonne Cancer Research Hospital was operated by the University of Chicago, under contract with the U.S. Atomic Energy Commission. References Griem, M.L., P. Lazarovits, and P.V. Harper. AExperience with Permanent Interstitial Implants Using Chromium-51 Sources.@American Journal of Roentgenology, Radiotherapy, and Nuclear Medicine. Vol. 120, No. 3, 1968, pp. 657B661. Griem, M.L., P. Lazarovits, and P.V. Harper. APreliminary Experience with Permanent Interstitial Implants Using Chromium-51 Sources.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 6, Part 29, 1968. Chicago: Argonne Cancer Research Hospital, pp. 30B37. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-39. Treatment of Selected Tumors Using an Electron Beam THIS RESEARCH at the Argonne Cancer Research Hospital involved development of a new technique for treating cancer using a high-energy electron pencil beam. An electron beam produced by a linear accelerator was directed into a scanning device positioned over the patients=tumor. Ninety-seven patients were treated between June 1959 and September 1962: 51 had malignancies of the head and neck, 8 had intrathoracic tumors, 5 had mycosis fungoides (a chronic, malignant disease of the lymphatic system), 1 had carcinoma of the thorax, 4 had urinary bladder carcinoma, 3 had benign lesions, and 25 had a variety of other cancerous lesions. Many of the procedures were performed for the alleviation of pain. The Argonne Cancer Research Hospital was operated by the University of Chicago, under contract with the U.S. Atomic Energy Commission. References Carpender, J.W.J., L.S. Skaggs, L.H. Lanzl, and M.L. Griem. ARadiation Therapy with High-Energy Electrons Using Pencil Beam Scanning.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 4, Part 20, 1963. Chicago: Argonne Cancer Research Hospital, pp. 47B56. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-40. Human Ingestion of Real and Simulated Fallout IN THE EARLY 1960s, the Argonne Cancer Research Hospital conducted studies on the human absorption and retention of radioactive materials (real or simulated fallout) taken into the body by ingestion. The purpose of these studies was to gain information that would be beneficial in civil defense planning. A total of 102 healthy, volunteer university students and hospital staff members participated as subjects. During the study, 10 study subjects ingested 0.2 to 0.7 microcurie of real fallout from the Nevada test site. Simulated fallout particles or radioactive solutions that contained 0.4 to 2.5 micro-curies of strontium-85 (Sr85) were also ingested by 45 subjects, 4.0 to 13.5 microcuries of barium-133 were ingested by 15 subjects, and 0.5 to 14.0 microcuries of cesium-134 were ingested by 32 subjects. Whole-body counting was performed to determine the amount of activity remaining in the subjects at various intervals after ingestion. There were no reports of any gastrointestinal symptoms after the test materials were ingested. These studies provided a basis for estimating the systemic uptake and internal radiation dose that could result from ingesting typical fallout soon after detonation of a nuclear weapon. This work was supported by the Office of Civil Defense and the U.S. Atomic Energy Commission. (This experiment was referenced in the Markey report.) References LeRoy, G.V., J.H. Rust, and R.J. Hasterlik. The Consequences of Ingestion by Man of Real and Simulated Fallout. Chicago: Argonne Cancer Research Hospital, ACRH-102. LeRoy, G.V., J.H. Rust, and R.J. Hasterlik. AThe Consequences of Ingestion by Man of Real and Simulated Fallout.@Health Physics. Vol. 12, 1966, pp. 449B473. " UC-41. Use of an Experimental Strontium90/Yttrium-90 Needle for Radiation Cordotomy Pain Relief IN THE EARLY 1960s, researchers at the Department of Neurological Surgery and Roentgenology, University of Chicago Hospital and Clinics collaborated with the Argonne Cancer Research Hospital to explore an alternative approach to high-risk surgical cordotomy. Surgical cordotomy (division of the sensory nerve tracts of the spinal column) has been performed since the early 1900s to alleviate severe pain. Sixty cordotomies, using strontium-90/yttrium-90 (Sr90/Y90) needles were performed by this method to relieve pain in a total of 42 patients (including both men and women) ranging in age from 3 to 71 years; of these, 37 had advanced malignant diseases of various types and 5 had benign conditions. Guided by xray pictures, a needle containing Sr90 and its decay product Y90 was inserted into the space between the first and second cervical vertebrae through the skin to divide the sensory nerve tracts of the spinal cord (cordotomy). The needle was held in place for 15 to 20 minutes in most cases, and up to 40 minutes in a few cases to deliver between 2,000 and 16,000 rads to the sensory tracts in the spinal cord. The procedure resulted in some pain relief among 34 of the 42 patients and eliminated the mortality risk and the long convalescent period associated with the surgical approach. This work was supported by the Douglas S. Smith and Simms Foundations, and the U.S. Public Health Service. The Argonne Cancer Research Hospital was operated by the University of Chicago, under contract with the U.S. Atomic Energy Commission. References Mullan, S., P.V. Harper, J. Hekmatpanah, H. Torres, and G. Dobbin. APercutaneous Interruption of Spinal Pain Tracts by Means of a Strontium-90 Needle.@Journal of Neurosurgery. Vol. 20, 1963, pp. 931B939. Mullan, S., P.V. Harper, E. Tane, G. Vailati, and K.A. Lathrop. AA Nuclear Needle for Use in Neurosurgery.@Journal of Neurosurgery. Vol. 20, 1963, pp. 940B947. Mullan, S., P.V. Harper, J. Hekmatpanah, H. Torres, and G. Dobbin. APercutaneous Cordotomy for Pain.@Semiannual Reports to the U.S. Atomic Energy Commission. Vol. 4, Part 20, 1963. Chicago: Argonne Cancer Research Hospital, pp. 37B46. The University of Chicago, Office of Legal Counsel, Semiannual Reports of the Argonne Cancer Research Hospital. " UC-42. Pharmacokinetics of Selenium75 |