Listing of Experiment Titles

University of Chicago - Argonne Cancer Research Hospital

UC-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 (Tc^99m) 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 Tc^99m.

Scans of subjects were made with a Picker Magnascanner 30 minutes after intravenous injection of Tc^99m. 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 Tc^99m. Thyroid scans were conducted on a clinically normal white male, 30 minutes after intravenous injection of Tc^99m, and the results were compared with scans conducted after iodine­131 (I¹³¹) administration. The urinary and fecal excretion of Tc^99m pertechnetate was studied in four patients. At least two normal subjects, including a healthy African­American male, were administered 440 microcuries of Tc^99m. Another male subject was administered 1 millicurie of Tc^99m and dose calculations were made for the total body, stomach, and thyroid.

With a biological retention half­time of 48 hours, Tc^99m 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-Tc^99m 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 Tc^99m 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 (Tc^99m 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 Tc^99m 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.  "

UC-26. Studies on the Radiation Sensitivity of Tumors in Normal Tissues After Chemically Induced Hyperthyroidism

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 (Tc^99m), and indium­113m (In^113m) 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.  "

UC-31. The Use of Yttrium-90 Pellets to Destroy the Pituitary Gland in Patients with Hormonally Influenced Cancers

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 Selenium­75BL-Selenomethionine

DURING THE EARLY 1970s, investigators at six institutions conducted collaborative studies on the pharmacokinetics of selenium-75 (Se⁷⁵)BL-selenomethionine as a new radiopharmaceutical for imaging the pancreas in nuclear medicine diagnostic exams. The studies were conducted at Argonne Cancer Research Hospital; Veterans Administration Hospital, Hines, Illinois; Roswell Park Memorial Institute, Buffalo, New York; Danbury Hospital, Danbury, Connecticut; Sloan-Kettering Institute for Cancer Research, New York; and the National Center for Radiological Health and Radioisotope Laboratory, University of Cincinnati.

A total of 40 subjects, comprising 30 patients with various diseases, including unspecified types of cancer, and 10 normal comparison subjects, participated in the study at one of the above-mentioned institutions.

Each subject received a single intravenous injection of approximately 250 microcuries of Se⁷⁵. At varying intervals after Se⁷⁵ administration, measurements of activity were made on samples of blood, urine, and feces collected from five subjects. Retained activity in the body was measured by whole-body counting of 24 subjects at four institutions over a period ranging from 3 up to 923 days. Selenium-75 concentrations were later measured in tissues obtained at autopsy from a total of 23 subjects at four of the institutions. Other radioactivity measurements were obtained from hair, nails, and skin.

The biological data obtained in these studies were combined for analysis to determine the radiation absorbed dose to the total body and to individual organs from Se⁷⁵-L-selenomethionine. The information was needed in assessing the usefulness of Se⁷⁵-L-selenomethionine as a tumor imaging agent. This work was supported in part by the U.S. Atomic Energy Commission.

References

Lathrop, K.A., R.E. Johnston, M. Blau, and E.O. Rothschild. ARadiation Dose to Humans from Se⁷⁵-L-Selenomethionine.@Journal of Nuclear Medicine. Suppl. No. 6, 1972, pp. 10B17.

ASummary of Current Radiation Dose Estimates to Humans from Se⁷⁵-L-Selenomethionine.@MIRD/Dose Estimate Report No. 1. January 1973.  "

UC-43. Experimental Use of Gallium-67 as a Scanning Agent in the Staging of Hodgkin=s Disease

IN 1971, physicians in the Section of Nuclear Medicine, Departments of Radiology, Medicine, and Surgery at the University of Chicago Hospitals and Clinics, Pritzker School of Medicine, and the Argonne Cancer Research Hospital collaborated to review the clinical diagnoses of 20 patients with suspected Hodgkin=s disease.

All 20 patients were evaluated using gallium-67 (Ga⁶⁷) as a scanning agent, followed by surgical exploration and tissue biopsies to confirm the diagnosis. Under the Ga⁶⁷ scanning protocol, 1.5 to 3.0 millicuries of Ga⁶⁷-citrate (less than 2 milliliters) were administered intravenously to each patient. The scan was performed 72 hours after the administration of Ga⁶⁷. The scan results were compared with the extent of the disease as determined by pathological examination of tissue samples obtained during surgery, and by chest radiographs.

The researchers concluded that Ga⁶⁷ was a useful supplement in Hodgkin=s disease staging, particularly because of its non-invasive methodology. This work was supported by the U.S. Public Health Service, the Junior Auxiliary of the University of Chicago Cancer Research Foundation, and the Goldblatt Brothers Employees=Nathan Goldblatt Cancer Research Fund. The Argonne Cancer Research Hospital was operated by the University of Chicago, under contract with the U.S. Atomic Energy Commission.

References

Turner, D.A., S.M. Pinsky, A. Gottschalk, P.B. Hoffer, J.E. Ultmann, and P.V. Harper. AThe Use of Ga⁶⁷ Scanning in the Staging of Hodgkin=s Disease.@Radiology. Vol. 104, No. 97, 1972. (Radiology reference)  "

University of Rochester

UR-1. Polonium-210 Metabolism and Excretion Study

DURING THE EARLY 1940s, the University of Rochester in New York conducted studies on the retention, excretion, and gastrointestinal tract absorption of polonium­210 (Po²¹⁰) in humans, using patients at Strong Memorial Hospital in Rochester, as subjects. The purpose of the study was to determine occupational exposure limits for use in radiation protection programs.

Five patients with advanced lymphoma or leukemia participated. Four of the patients were administered an intravenous injection of 8 to 23 microcuries of Po²¹⁰ and one patient was orally administered 18.5 microcuries of Po²¹⁰ in tap water. Urine samples were subsequently collected and analyzed for Po²¹⁰.

All subjects died of preexisting ailments shortly after the administrations. Tissues were obtained at autopsy and examined for Po²¹⁰ concentration. This research was supported by the Manhattan Engineer District. (This experiment was referenced in the Markey report and included in The DOE Roadmap of February 1995.)

References

Fink, R.M. ABiological Studies with Polonium, Radium, and Plutonium.@National Nuclear Energy Series. Div. 6, Vol. 3. New York: McGraw­Hill, 1950.

Stannard, J.N. Radioactivity and Health: A History. Office of Scientific and Technical Information. 1988, pp. 213B214.  "

UR-2. Uranium Injections

FROM AUGUST 1946 TO JANUARY 1947 , the University of Rochester conducted toxicity studies on uranium, using hospital patients as subjects. The purpose of the studies was to determine the dose level at which renal injury is first detectable, measure the rate at which uranium is eliminated from the body once it enters the bloodstream, and observe the effect of measures intended to alter the excretion rate.

Subjects included four males and two females, all with good kidney function, ranging in age from 24 to 61 years. All had medical conditions, such as undernutrition, alcoholism, or heart disease.

Highly enriched uranium (uranium­234 and uranium­235) was administered intravenously as uranyl nitrate in amounts ranging from 6.4 to 70.9 micrograms per kilogram of body weight. At levels approaching 50 micrograms per kilogram, the preparation was diluted with natural uranyl acetate to limit the potential radiotoxicity associated with systemic enriched uranium. Five subjects received a single injection and experienced no kidney damage. The sixth subject experienced slight kidney tissue toxicity at the 70.9 micrograms-per-kilogram level, suggesting that the human tolerance level had been reached. This patient was administered ammonium chloride to induce an acidosis condition (a decrease in alkali relative to acid in bodily fluids), then received a second injection of uranyl nitrate at a dose of 56.6 micrograms per kilogram.

These studies showed that the tolerance level for uranium in the human circulation was about 70 micrograms per kilogram of body weight, that uranium excretion occurred mainly through urine, that 70 to 85 percent was eliminated in the first 24 hours, and that acidosis decreased the rate of uranium excretion. This research was supported by the Manhattan Engineer District. (This experiment was referenced in the Markey report and included in The DOE Roadmap of February 1995.)

References

Bassett, S.H., A. Frankel, N. Cedars, H. Van Alstine, C. Waterhouse, and K. Cusson. The Excretion of Hexavalent Uranium Following Intravenous Administration. II. Studies on Human Subjects. Rochester: The University of Rochester, UR­37, June 1948.  "

UR-3. Ingestion of Milk Containing Iodine­131

THIS STUDY WAS CONDUCTED in 1963 by a graduate student at the University of Rochester to investigate the body=s metabolism of radioiodine found in dairy products. The research sought to determine whether iodine found in milk was transferred to the thyroid in the same quantities as the inorganic iodide commonly used in medical studies. As much as 40 percent of the iodine found in milk was found to be protein bound. The study focused on the range of uptake percentages in children of various ages.

Subjects for the experiment were chosen with an emphasis on the younger age groups, since the majority of known research had been conducted on adults. The subjects ranged in age from 6 years to 50 years; seven were less than 21 years old. The milk used for this study was obtained from Cornell University=s Department of Veterinary Medicine, where a cow had been fed iodine­131 (I¹³¹) so as to produce 5 to 10 nanocuries per liter in its milk.

All subjects were put on an iodine-restricted diet prior to the study and then were fed the I¹³¹ milk for a minimum of 14 days. One of the children in this study subsequently developed a benign nodular hyperplasia of the thyroid, which was later surgically removed. The research was performed under a contract with the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

Cuddihy, R.G. AHazard to Man from I¹³¹ in the Environment.@Health Physics. Vol. 12, 1966, pp. 1,021B1,025.

Correspondence. T.S. Ely to W. LeFurgy and D.R. Fisher. February 14, 1995.  "

UR-4. The Fate of Radon Ingested by Humans

In 1964, the Department of Radiation Biology at the University of Rochester conducted a study on the fate of radon ingested by humans. Two male subjects, ages 36 and 56, participated.

On two occasions, each subject drank approximately 1 microcurie of radon­222 (Rn²²²) in equilibrium with its decay products in 100 milliliters of water. On 3 separate days, the ingestions of radon were followed by a normal breakfast; the fourth followed a larger breakfast high in fat. The subject=s respired air, blood, and urine were obtained and sampled for Rn²²² activity.

This study provided rates at which the body loses radon and the impact of stomach contents on the rate of loss. The research was supported by the U.S. Atomic Energy Commission. (Previously described in #29 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Hursh, J.B., D.A. Morken, T.P. Davis, and A. Lovaas. AThe Fate of Radon Ingested by Man.@Health Physics. Vol. 11, 1965, pp. 465B476.  "

 ‡  ‡  ‡

UR-5. Excretion Studies Using Thorotrast Containing Thorium-232 and Decay Products

BETWEEN 1930 AND 1945, researchers at the University of Rochester, New York and the National Naval Medical Center, Bethesda, Maryland, conducted studies on the human excretion of thorium, and its daughter isotopes of radium, using Thorotrast, a contrast medium containing thorium-232 (Th²³²) and its radioactive decay products.

Five hospital patients (men and women) were administered 40 to 75 milliliters of Thorotrast by injection, equivalent in total alpha-particle activity to about 2.1 microcuries of radium-226. The activity of Th²³² and its decay products: radium-228; thorium-228; and radium-224 was measured in body tissues, urine, and feces samples for up to 19 years post-injection.

These studies indicated that thorium is retained in the body with a biological retention half-time of about 400 years. This work facilitated the estimates of radiation absorbed dose to various organs (liver, spleen, bone marrow, and lung) from Thorotrast. This work was supported in part by the U.S. Atomic Energy Commission.

References

Hursh, J.B., L.T. Steadman, W.B. Looney, and M. Colodzin. AThe Excretion of Thorium and Thorium Daughters After Thorotrast Administration.@Acta Radiologica. Vol. 47, JanuaryBJune 1957, pp. 481B498.  "

UR-6. Radon-222 Inhalation Studies

IN APPROXIMATELY 1956, radon inhalation studies were performed by researchers at the Department of Radiation Biology of the University of Rochester School of Medicine and Dentistry, New York. The purpose of these studies was to determine the radiation doses to various parts of the human respiratory system from inhaled radon and its decay products.

Radon-222 (Rn²²²), obtained from a 50-microcurie radium chloride source, was introduced into an exposure chamber by water displacement. Two subjects breathed (by mouth only) air from the chamber containing about 0.025 microcurie of Rn²²². The air was typical of either normal room air (with normal dust loadings) or air filtered to remove normal dust. The radon daughter activity in the air exhaled by the subjects was compared to the radon daughter activity of the air in the chamber. Radon daughter product retention from normal dusty air was compared with retention from filtered air.

The average retention of the daughter products in air containing normal atmospheric dust was 25 percent, while the average retention in filtered air breathed by the subjects was 75 percent.

The radiation doses to the lungs of the subjects were calculated using the data obtained. The average radiation dose to lungs, as a whole, was estimated to be 4.9 millirads per week of 168 hours for normally dusty air. Data were insufficient to estimate the dose due to radon and its decay products in very clean (dust-free) air.

The investigators concluded that radiation exposure to the lungs from breathing an atmosphere containing radon is usually due to radon daughters rather than radon itself. This work was supported by the U.S. Atomic Energy Commission.

References

Shapiro, J. ARadiation Dosage from Breathing Radon and its Daughter Products.@A.M.A. Archives of Industrial Health. Vol. 14, No. 2, August 1956, pp. 169B177.  "

UR-7. Study of the Retention and Distribution of Thorium-232 Decay Products

BETWEEN 1960 AND 1964, a study was conducted at the University of Rochester, New York to determine the retention and biological distribution of thorium-232 (Th²³²) and its decay products. Thorium-232 is the principal component of Thorotrast, a colloidal thorium oxide contrast agent used in diagnostic radiology. The purpose of this study was to learn more about the long-term retention and dosimetry of thorium decay products in patients who received thorotrast.

For this study, a group of four elderly volunteer subjects was chosen. Each of the subjects received an intravenous injection of 24 milliliters of Thorotrast. The amount of Th²³² and daughter product activity administered was not stated. Each subject was then periodically monitored in a whole-body counter up to 4 years post-injection to determine the amounts of the Th²³² decay products actinium-228 and thallium-208 remaining in their bodies.

Breath measurements for exhaled thoron (radon-220) were also made on two of the four subjects during the study period. These measurements provided estimates of the body contents of other Th²³² decay products, including radium-228, thorium-228, and radium-224. Breath measurements showed that 9 percent of the thoron formed as a decay product in the body escaped in expired air. The lung dose to study participants was estimated to have been between 15 and 45 rems per year. This work was supported by the U.S. Atomic Energy Commission.

References

Hursh, J. B. ABody Content of Thorium-232 Daughters after Thorotrast Injection.@Annual Report, University of Rochester, Atomic Energy Project, Brief Description of Most of the Research Programs Completed During 1964. Rochester, NY: University of Rochester, Atomic Energy Project, UR-668, September 1, 1965, pp. 82B84.

Hursh, J.B. ALoss of Thorium Daughter by Thorium Dioxide Patients.@Annals of the New York Academy of Sciences, Vol. 145, 1967, pp. 634B641.  "

UR-8. Study of the Metabolism of Natural Uranium in the Human Skeleton

BETWEEN 1960 AND 1964, scientists at the University of Rochester, New York conducted experiments on the metabolism of uranium in the human skeleton. Subjects for this study included 10 patients at the University=s hospital metabolism ward. They included three patients with bone disease (osteoporosis or osteomalacia), one with Paget=s disease of bone, one with hyperparathyroidism plus a parathyroid adenoma, and one with hypoparathyroidism. About 1.5 to 2.0 milligrams natural (not enriched) uranium were administered intravenously as the soluble uranyl ion (UO₂⁺⁺) to subjects following breakfast. Some of the subjects received multiple uranium injections over time. Measurements were later made to determine the rates of urinary uranium excretion by the subjects. Serum calcium was also measured to determine the effect of uranium on blood calcium levels.

These studies suggested that measurements of the uptake and release of uranium by bone, when compared to calcium uptake and release, could be a useful indicator of metabolic bone disease in man. This work was supported by the U.S. Atomic Energy Commission.

References

Terepka, A.R., T.Y. Toribara, and W.F. Neuman. ASkeletal Retention of Uranium in Man.@Proceedings of the 46th Meeting of the Endocrine Society, June 18, 1964, San Francisco. In Proceedings, 1965.

Terepka, A.R. Dynamic Aspects of Skeletal Metabolism in Man. Rochester, NY: University of Rochester, Final Report of Contract AT (30-1)-1981, TID-22324,1965.

Terepka, A.R. ADynamic Aspects of Skeletal Metabolism.@In Annual Report, University of Rochester, Atomic Energy Project, Brief Description of Most of the Research Programs Completed During 1964. Rochester, NY: University of Rochester, Atomic Energy Project, UR-668, September 1, 1965, pp. 92B94.  "

UR-9. Use of Antibodies Labeled with Iodine-131 in the Diagnosis and Localization of Brain Tumors

IN 1962, the National Institute for Neurological Diseases and Blindness (NINDB) in Bethesda, Maryland, the Neurological Institute of Columbia University, New York, and the Strong Memorial Hospital (SMH) in Rochester, New York, under the direction of the Department of Radiation Biology at the University of Rochester, conducted a study of antibodies labeled with iodine-131 (I¹³¹) for diagnosing and locating brain tumors.

A total of 28 patients were intravenously injected with I¹³¹ antibody. All patients had known extensive malignant disease or known or strongly suspected brain tumors. Most patients received 400 to 500 microcuries of I¹³¹ attached to antibody in a volume of 5 to15 milliliters of solution. Antibody content (rabbit gamma globulin) ranged from 0.15 to 0.8 milligram of protein per dose.

The investigators at NINDB found that, for sarcomas (18 patients), there was a good probability of a fairly specific uptake of I¹³¹-labeled antibody compared with I¹³¹-labeled human albumin. Analysis of blood samples from the five patients studied at SMH showed a biological half-time in blood of 4.3 days. External scanning and biopsy studies did not indicate localization of radioactivity in tumors outside the brain great enough to be of diagnostic or therapeutic significance. Scintillation scanning of the head of patients with brain tumors indicated that preparations of this type may be useful for diagnosis and delineation of these lesions. This work was performed under contract with the U.S. Atomic Energy Commission.

References

Spar, I.L., W.F. Bale, R.L. Goodland, and M.J. Izzo. APreparation and Human Studies with I¹³¹-Labeled Antibody Reacting With Fibrin.@AEC Research and Development Report. Rochester, NY: University of Rochester, Atomic Energy Project, August 9, 1962, UR-614. University of Rochester, Office of Scientific and Technical InformationCUnclassified Vault.  "

UR-10. Skeletal Metabolism of Calcium-45 and Sodium-22

IN 1964, researchers at the University of Rochester, New York conducted a study on the kinetics of short-term blood disappearance and skeletal metabolism of calcium-45 (Ca⁴⁵) and sodium-22 (Na²²). The purpose of this study was to develop new approaches for studying the metabolism of calcium and sodium in the human skeleton.

Thirteen patients, some with bone disease, were admitted to the University=s medical center metabolism ward for participation in this study. The amounts of Ca⁴⁵ and Na²² administered to each subject were not stated. Measurements were made at frequent intervals after injection to determine the concentrations of Ca⁴⁵ and Na²² in circulating blood. From these data, the size of the rapidly exchangeable calcium compartment involved in blood-to-bone mineral exchange was determined.

This study showed that Ca⁴⁵ and Na²² tracers provided useful tools for evaluating and diagnosing diseases of the skeleton in man. This research was supported by the U.S. Atomic Energy Commission.

References

Terepka, A.R. Dynamic Aspects of Skeletal Metabolism in Man. Rochester, NY: University of Rochester, Atomic Energy Project, Final Report of Contract AT (30-1)-1981, TID-22324, 1965.

Terepka, A.R. ADynamic Aspects of Skeletal Metabolism.@InAnnual Report, University of Rochester, Atomic Energy Project, Brief Description of Most of the Research Programs Completed During 1964. Rochester, NY: University of Rochester, UR-668, September 1, 1965, pp. 92B94.  "

UR-11. Lead-212 Absorption Studies

BETWEEN 1966 AND 1967, researchers in the Department of Radiation Biology and Biophysics at the University of Rochester School of Medicine and Dentistry, New York in collaboration with the Special Laboratories of Statens StrDlskyddsinstitut (the Swedish Radiation Protection Institute), Stockholm, studied the absorption of lead-212 (Pb²¹²) from the gastrointestinal tract. The purpose of the study was to determine the radiation hazard and chemical toxicity hazard of ingested lead.

Of the four Swedish volunteers, two received oral, one received intravenous, and one received both intravenous and oral administrations of Pb²¹². The amounts of activity administered intravenously and orally were approximately 1 and 5 microcuries, respectively. The Pb²¹² excretion of these subjects was measured within 24 hours to determine Pb²¹² absorption from the gastrointestinal tract. The average absorption was 8 percent, which was equal to the value previously reported by the International Commission on Radiological Protection. In addition to absorption studies, Pb²¹² uptake by red blood cells also was determined.

The researchers concluded that lead might be released from the binding sites only when red cells die. This work was funded in part by the National Institute of Arthritic and Metabolic Diseases. The Department of Radiation Biology and Biophysics at the University of Rochester was supported, in part, by the U.S. Atomic Energy Commission.

References

Hursh, J.B. AAbsorption of Pb²¹² from the Gastrointestinal Tract of Man.@In Proceedings of the 13th Annual Bioassay and Analytical Chemistry Meeting.Berkeley, CA: Lawrence Radiation Laboratory, University of California, October 12B13, 1967, April 1968, UCRL-18140.

Hursh, J.B., and J. Suomela. AAbsorption of Pb²¹² from the Gastrointestinal Tract of Man.@Acta Radiologica. Vol. 7, pp. 108B120, 1968.  "

Other

OT-1. Study of Blood Volumes with Iodine­131B Tagged Plasma Protein

CASE WESTERN RESERVE UNIVERSITY conducted this study in 1950. Blood volume determinations were made on 76 ambulatory hospital patients who exhibited normal fluid and protein balance. The subjects were injected with plasma protein tagged with iodine­131 (I¹³¹) while they were fasting. They were confined to bed until the experiment was completed.

Approximately 40 to 60 microcuries of I¹³¹ were intravenously injected. Twelve patients who were to receive spinal anesthesia were also given radioactive iodinated protein at various intervals, preceding the administration of the anesthesia. No radioactivity was detected in the spinal fluid of these patients.

The studies on the patients confined to bed showed that an average of 8 to 12 percent of the injected radioactive iodine was found in the urine within 24 hours of the injection. This research was partly supported by a U.S. Atomic Energy Commission contract. (Included in The DOE Roadmap of February 1995)

References

Storaasli, J.P., H. Krieger, H.L. Friedell, and W.D. Holden. AThe Use of Radioactive Iodinated Plasma Protein in the Study of Blood Volume.@American Journal of Obstetrics & Gynecology. Vol. 91, October 1950, pp. 458B464.

Storaasli, J.P., H. Krieger, H.L. Friedell, and W.D. Holder. The Use of Plasma Protein Tagged Iodine­131 in the Study of Blood Volumes. Cleveland: Western Reserve University, NYO­1608, July 6, 1950.  "

OT-2. The Use of Iodine-131BLabeled Human Serum Albumin to Evaluate the Peripheral Circulation

THIS RESEARCH WAS carried out in 1952 at Case Western Reserve University. Human serum albumin labeled with iodine­131 was injected into 77 subjects and a scintillation counter was used to determine cardiac output and to observe peripheral vascular flow.

Approximately 150 microcuries of radioiodinated albumin were injected into the subjects. A series of these experiments were performed on young subjects with normal circulation. Four of the young subjects had one foot immersed in hot water for 20 minutes before the labeled albumin was injected into them. In two other subjects, the foot was immersed in ice water for 10 minutes before the test was performed. The study was carried out under contract with the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

Krieger, H., J.P. Storaasli, W.J. MacIntyre, W.D. Holden, and H. Friedell. AThe Use of Radioactive Iodinated Human Serum Albumin in Evaluating the Peripheral Circulation.@Annals of Surgery. Vol. 136, No. 3, September 1952, pp. 357B365.

MacIntyre, W.J., J.P. Storaasli, H. Krieger, W.H. Pritchard, and H.L. Friedell. I¹³¹-Labeled Serum AlbuminCIts Use in the Study of Cardiac Output and Peripheral Vascular Flow.Cleveland: Western Reserve University, NYO­1642, March 11, 1952.  "

OT-3. Use of Iodine-131BLabeled Protein in the Study of Protein Digestion and Absorption in Children With and Without Cystic Fibrosis of the Pancreas

THIS STUDY WAS PERFORMED in 1952 at Case Western Reserve University. During the two decades prior to the study, several studies of protein digestion and absorption had been carried out both in normal individuals and in patients with various diseases. This study describes a simple and accurate method to determine the efficiency of protein digestion and absorption, by measuring the isotope content of the feces after oral ingestion of protein labeled with iodine­131 (I¹³¹).

The subjects were 10 children with diseases that did not specifically involve the gastrointestinal tract and 5 children with cystic fibrosis of the pancreas. The subjects ranged in age from 1.6 years to 9 years. These patients fasted for 12 hours before the experiment; then, a test meal containing I¹³¹ was given in place of breakfast. The test meal contained approximately 1 microcurie of labeled protein per kilogram of body weight. In the five children with cystic fibrosis of the pancreas, pancreatin was withheld for 3 days prior to and during the initial test.

The research demonstrated a diminished retention of dietary protein in cystic fibrosis of the pancreas. This research was supported by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

Lavik P.S., L.W. Matthews, G.W. Buckaloo, F.J. Lemm, S. Spector, and H.L. Friedell. AUse of I¹³¹-Labeled Protein in the Study of Protein Digestion and Absorption in Children with and without Cystic Fibrosis of the Pancreas.@Pediatrics. Vol. 10, 1952, pp. 667B675.

Lavik, P.S., L.W. Matthews, G.W. Buckaloo, S. Spector, and H.L. Friedell. Use of I^131-Labeled Protein in the Study of Protein Digestion and Absorption in Children with and without Cystic Fibrosis of the Pancreas. Cleveland: Western Reserve University, NYO­4025, August 15, 1952.  "

OT-4. Thyroidal Deposition of Iodine-131 in Humans, Rats, and Dogs, from Milk and Nonmilk Sources

IN 1963, Cornell University conducted studies on the comparative uptake of iodine from ingested water and milk, using human and animal subjects. Eleven healthy male volunteers ranging in age from 26 to 52 years participated and ingested 0.1 liter of milk containing iodine­131 (I¹³¹). The study used milk obtained from cows that had been fed I¹³¹ 2 days prior to milk collection. The milk contained approximately 2.5 microcuries of I¹³¹ per liter. Inorganic I¹³¹ was administered with 100 milliliters of water containing about 0.26 microcurie of I¹³¹.

Results of the study indicated that there was no significant difference in the uptake of iodine in humans when obtained through milk or water. This work was supported by the U.S. Atomic Energy Commission. (Previously described in #47 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Comar, C.L., R.A. Wentworth, and J.R. Georgi. AThyroidal Deposition in Man, Rat, and Dog of Radioiodine from Milk and Non­Milk Sources.@Health Physics. Vol. 9, 1963, pp. 1,249B1,252.  "

OT-5. Plasma Volume Studies Using Chromium-51BChloride

THIS RESEARCH WAS CONDUCTED at the Biophysical Laboratory and the Department of Medicine at Harvard Medical School and the Medical Clinic at Peter Bent Brigham Hospital in Boston. Approximately 100 microcuries of chromium­51 as chromium chloride were intravenously injected into 26 normal adults (5 women and 21 men).

After allowing 5 minutes for mixing within the circulation, researchers drew four samples of blood and analyzed them in a gamma counter to determine plasma volumes. The plasma volumes were determined by this method. In some subjects, a second study was also performed. This method was further tested by measuring the plasma volume before and after transfusion or hemorrhage of between 250 and 500 milliliters of plasma in hospital patients and volunteer subjects. This research was supported in part by the U.S. Atomic Energy Commission and in part by the U.S. Public Health Service. (Included in The DOE Roadmap of February 1995)

References

Frank, H., and S.J. Grey. AThe Determination of Plasma Volume in Man with Radioactive Chromic Chloride.@Journal of Clinical Investigation. Vol. 32, No.10, 1953, pp. 991B999.  "

OT-6. Iodine-131 Uptake by the Human Embryo

IN 1953, studies were conducted at the University of Iowa, Iowa City on the uptake of iodine­131 (I¹³¹) in thyroids of human embryos in utero. (The number of subjects is not known.)

Pregnant women scheduled for therapeutic abortions were given dosages of 100 to 200 microcuries of I¹³¹. Some time later, the abortions were performed. The aborted embryos were sectioned and autoradiographed. The human embryos showed thyroid uptake at 4 weeks, nearly 1 month earlier than was previously known. This finding was useful in understanding the transfer of radioiodine across the placental barrier.

This study showed that it would not be prudent to administer I¹³¹ to pregnant women for diagnostic or therapeutic purposes. This work was funded by the U.S. Atomic Energy Commission. (Previously described in #5 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

U.S. Atomic Energy Commission. Monthly Status and Progress Report Division of Biology and Medicine. Iowa City, IA: University of Iowa, June 1953. U.S. Department of Energy Archives, Record Group 326, Division of Biology and Medicine, Box 3363, Folder 23.  "

OT-7. Uptake of Iodine-131 in Normal Newborn Infants in Iowa City

IN 1963, the University of Iowa, Iowa City conducted studies on the uptake of iodine-131 (I¹³¹) in newborn infants. Twelve male and 13 female infants were included in this study. All were less than 36 hours old, weighed between 5.5 and 8.5 pounds, and were considered to be healthy and normal.

Less than 1 microcurie of iodine-131 (I¹³¹) was administered to each newborn. Eight received the radioiodine orally and 17 by intramuscular injection. The concentration of I¹³¹ in the thyroid was measured using a thyroid gamma probe. Measurements were continued at intervals of 2 to 8 hours for 3 to 4 days.

This study showed that I¹³¹ was taken up by the thyroid at a higher level and more rapidly when administered by injection rather then ingestion. This study was supported by the U.S. Atomic Energy Commission and the American Cancer Society. (Previously described in #4 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Morrison, R.T., J.A. Birkbeck, T.C. Evans, and J.I. Routh. ARadioiodine Uptake Studies Newborn Infants.@Journal of Nuclear Medicine. Vol. 4, 1963, pp.162B166.  "

OT-8. Uptake of Iodine-131 in Normal Newborn Infants in Nebraska

THE THYROID FUNCTIONof infants was studied jointly by the Veterans Administration Hospital, Omaha, Nebraska, and the Department of Radiology, University of Nebraska, College of Medicine, in 1960. Twenty­eight normal, healthy infants from the nursery at the College of Medicine, including 16 males and 12 females ranging in age from 72 to 180 hours, were involved in the experiment.

Each of the newborn infants was given 5 microcuries of iodine­131 (I¹³¹) through a gastric tube. The concentration of I¹³¹ in the thyroid was measured 24 hours later.

This study showed that the thyroid of a newborn functioned similarly to those of adult thyroids. The subject=s sex and weight were not related to thyroid function. (Previously described in #4 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Ogborn, R.E., R.E. Waggener, and E. VanHove. ARadioactive­Iodine Concentration in Thyroid Glands of Newborn Infants.@Pediatrics. Vol. 26, November 1960, pp. 771B776.  "

OT-9. Uptake of Iodine-131 in Normal Newborn Infants in Memphis

IODINE-131 WAS USED to study the uptake of iodine in normal, newborn infants at the University of Tennessee and at the John Gaston Hospital in Memphis, in approximately 1952 to 1954. Seven male infants (one white and six black) between 2 and 3 days old were injected intravenously with 1.0 to 1.5 microcuries of iodine-131 (I¹³¹). The concentration of I¹³¹ in the thyroid was measured 24 hours after injection. Absorbed doses to the infant thyroids were estimated to be about 60 rads.

The I¹³¹ uptake of the thyroid of the subjects was found to lie within the range of values that would be found in hyperthyroid adults. This study was supported by a grant from the U.S. Atomic Energy Commission. (Previously described in #4 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Van Middlesworth, L. ARadioactive Iodide Uptake of Normal Newborn Infants.@AMA American Journal of Diseases of Children. Vol. 88, October 1954, pp. 439B442.  "

OT-10. Radioactive Isotope Studies at Tulane

IN THE LATE 1940s and early 1950s, a series of metabolic experiments was conducted at Charity Hospital and Tulane University School of Medicine, New Orleans, LA. The focus of the experiments was to investigate the role of electrolytes in normal humans and in patients with congestive heart failure. The total number of subjects is not specified, but as many as 269 people could have been included in the study. Some of these subjects may have participated in more than one study.

The radioisotope studies examined retention times, excretion rates, biologic decay rates, and a variety of other physiological parameters. The radioisotopes used included mercury­203. One subject received only x­rays to determine the effects of radiation on humans. (Previously described in #8 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Burch, G.E., P.B. Reaser, and J.A. Cronvich. ARates of Sodium Turnover in Normal Subjects and in Patients with Congestive Heart Failure.@The Journal of Laboratory and Clinical Medicine. Vol. 32, No. 10, 1947, pp. 1,169B1,191.

Burch, G.E., S.A. Threefoot, and P.B. Reaser. ASome Aspects of Renal Excretion of Na²⁴ by Normal Subjects and by Patients with Congestive Heart Failure.@Stanford Medical Bulletin. Vol. 6, No. 1, 1948, pp. 81B87.

Burch, G.E., S.A. Threefoot, J.A. Cronvich, and P.B. Reaser. ATheoretic and Experimental Considerations of Biological Decay Periods: Studies in Man with the Use of Na²².@In Cold Spring Harbor Symposia On Quantitative Biology. Vol. 13, 1948, pp. 63B74.

Burch, G.E., S.A. Threefoot, and P.B. Reaser. AAspects of the Biological Decay Periods of Sodium in Normal and Diseased Men.@Science. Vol. 107, 1948, pp. 91B92.

Burch, G.E., R.S. Sohal, S. Sun, G.C. Miller, and H.L. Colcolough. AEffects of Radiation on the Human Heart.@Archives of Internal Medicine. Vol. 221, 1968, pp. 230B234.  "

OT-11. Iron Metabolism in Human Pregnancy as Studied with Iron-59

FROM 1945 THROUGH 1949, Vanderbilt University Hospital conducted studies on iron absorption in pregnant women. Participants in the study were part of a larger nutrition survey conducted by the hospital.

In all, 829 normal, healthy, pregnant women ingested radioactive iron­59 (Fe⁵⁹) in an amount ranging from 1.8 to 120 milligrams. The Fe⁵⁹ was administered at various times in the gestation period ranging from fewer than 10 to more than 35 weeks. Radioactivity in the blood was measured 2 weeks and, again, 3 weeks after administration.

The study showed that iron uptake is related to both dosage level and gestation period. The percentage of absorption decreased as the amount administered went up, while the actual amount of iron absorbed increased. Also, uptake increased later in the gestation period. At 30 weeks, three times as much iron was absorbed as at 15 weeks. This research was supported by the Nutrition Foundation, Inc., the Rockefeller Foundation, and the Tennessee State Department of Health.

From 1964 to 1967, Vanderbilt University School of Medicine conducted a follow­up study on the children born to these women. The study included 679 children of mothers who had been fed Fe⁵⁹ and 705 children of mothers in the original study control population. One case of leukemia and two cases of sarcoma were discovered in the Fe⁵⁹ population. There were no malignancies in the control population. Compared to an expected incidence of less than one, the three cases are statistically significant. There were no differences in malignancies among the mothers, congenital defects among the children, or congenital defects among subsequent children between the two populations. This follow­up work was supported by the U.S. Public Health Service and the U.S. Atomic Energy Commission. (Previously described in #1 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Hagstrom, R.M., S.R. Glasser, A.B. Brill, and R.M. Heyssel. ALong-Term Effects of Radioactive Iron Administered During Human Pregnancy.@American Journal of Epidemiology. Vol. 90, No. 1, pp. 1B10.

Hahn, P.F., E.L Carothers, W.J. Darby, M. Martin, C.W. Sheppard, R.O. Cannon, A.S. Beam, P.M. Densen, J.C. Peterson, and G.S. McClellan. AIron Metabolism in Human Pregnancy as Studied with the Radioactive Isotope, Fe⁵⁹.@American Journal of Obstetrics and Gynecology. Vol. 61, No. 3, March 1951, pp. 477B486.

Pribilla, W., T.H. Bothwell, and C.A. Finch. AIron Transport to the Fetus in Man.@In Symposium on Iron in Clinical Medicine, edited by R.O. Wallerstein and S.R. Mettier, pp. 58B64. Berkeley, CA: University of California Press, 1958.  "

OT-12. Sodium-24 Used to Study Exchangeable Sodium in Relation to the Menstrual Cycle

THIS STUDY WAS CONDUCTED in 1969 at Vanderbilt University. Six healthy female volunteers, between the ages of 19 to 44 years, with no history of hypertension and with normal blood pressure, were fed a constant sodium diet for 30 to 45 days.

After administration of a 10 microcuries oral dosage of sodium­24 (Na²⁴), exchangeable sodium spaces were measured during the follicular phase and the luteal phase of the menstrual cycle. The subjects were followed daily at the Clinical Research Center for excretion of sodium, potassium and creatinine; urine volume; body weight; and basal body temperature. This research was funded by grants from the U.S. Public Health Service, the American Heart Association, and the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

Brill, A.C. AEC Progress Report: Radiation Dosimetry and Biological Turnover of Radionuclides Used in Nuclear Medicine in Prenatal and Postnatal Subjects Using Stable and Radioactive Tracer. Nashville: Vanderbilt University, October 31, 1969. Oak Ridge Operations Office, Public Reading Room/Public Information Office, RHA Shipment 9162, Box 6 and 7, New York Times FOIA Requests, pp. 88B91.  

Michelakis, AM., E.G. Stant, and A.B. Brill. ASodium >Space=and Electrolyte Excretion During the Menstrual Cycle.@American Journal of Obstetrics & Gynecology. Vol. 109, No. 1, January 1, 1971, pp. 150B154.  "

OT-13. Blood Volume Measurements Using Stable Chromium-50 and Radioactive Chromium-51

STUDIES WERE CONDUCTED at Vanderbilt University in Nashville during the period 1969 to1972 on methods for diagnosing intracranial hemorrhage in newborn infants suffering with respiratory distress. The red blood-cell volume and estimated time of intracranial hemorrhage was determined using chromium isotope labeling techniques. The purpose of this research was to develop tracer techniques for determining blood volumes in patients using the stable isotope chromium­50 (Cr⁵⁰).

After blood labeled with stable Cr⁵⁰ was removed from the patient, it was irradiated with neutrons, and the activated products (chromium-51[Cr⁵¹] and iron-59) were measured by gamma-ray analysis. To conduct this study, it was necessary to calibrate and compare with results previously obtained using standard Cr⁵¹ blood volume analysis. Therefore, at the start of the study, the total red blood-cell volume in one infant and three adult patients was measured using both Cr⁵⁰ and Cr⁵¹ tracers as sodium chromate.

This study showed that stable Cr⁵⁰ could be used in place of Cr⁵¹ in blood volume analyses to preclude the need to use a radioactive tracer in newborn infants. This study was supported in part by a U.S. Atomic Energy Commission contract and in part by a grant from the National Heart Institute. (Included in The DOE Roadmap of February 1995, and since revised)

References

Brill, A.B. AEC Progress Report Radiation Dosimetry and Biological Turnover of Radionuclides Used in Nuclear Medicine in Prenatal and Postnatal Subjects Using Stable and Radioactive Tracers. Nashville: Vanderbilt University, October 31, 1969. Oak Ridge Operations Office, Public Reading Room/Public Information Office, RHA Shipment 9162, Box 6 and 7, New York Times FOIA Requests 88B91.

Dyer, N.C., A.B. Brill, G. Faxelius, and M. Stahlman. ABlood Volume and Hemorrhage Timing in Newborn Infants with Respiratory Distress using the Stable Tracer Cr⁵⁰.@In Neutron Sources and Applications: Proceedings of the Nuclear Society National Topical Meeting in Augusta, Georgia, April 19B21, 1971. April 18, 1971, pp. V­46BV­52.

Dyer, N.C., A.B. Brill, A.K. Tsiantas, E. Sell, L.H. Victorin, and M.T. Stahlman. ATiming of Intracranial Bleeding in Newborns and Infants.@Journal of Nuclear Medicine.Vol. 14, No. 11, November 1973, pp. 807B811.  "

OT-14. Testicular Irradiation of Washington State Prison Inmates

FROM 1963 TO 1973, the University of Washington, Seattle conducted studies on the effects of radiation on human testicular function using inmates at the Washington State Prison in Walla Walla, as subjects. Initially, 232 healthy volunteers were accepted into the study program.

Sixty were subsequently irradiated with acute doses of x­rays, ranging from 7.5 to 400 rads to the testes. Four other participants went through an identical procedure, but received no radiation. Forty­three were released from the program for a variety of reasons. The remaining 125 inmates served as control subjects in the study. Each inmate selected for the study had expressed a desire to undergo a vasectomy at the conclusion of the study. Fifty­three subjects received post­study vasectomies. The other 11 subjects either declined the procedure or did not receive vasectomies. Tissue samples were analyzed at the Biology Division of Oak Ridge National Laboratory.

These studies showed that doses of 7.5 rads had no adverse effect on testicular function, that doses of 27 rads inhibited generation of sperm cells, that doses of 75 rads destroyed existing sperm cells, and that doses of 100 to 400 rads produced temporary sterility. All subjects of the study eventually recovered to their normal preirradiation condition prior to vasectomy.

Study results showed that adult males are very radiosensitive to temporary sterility, but also radioresistant to complete sterility. This work was supported by the U.S. Atomic Energy Commission. (This experiment was referenced in the Markey report and included in The DOE Roadmap of February 1995.)

References

Paulsen, C.A. The Study of Irradiation Effects on the Human Testis: Including Histologic, Chromosomal and Hormonal Aspects. Seattle: University of Washington School of Medicine, January 31, 1973. Terminal Report, AEC Contract #AT(45­1)­2225.

Thorslund, T.W., and C.A. Paulsen. AEffects of X­Ray Irradiation on Human Spermatogenesis.@In Proceedings of the National Symposium on Natural and Man­Made Radiation in Space, edited by E.A. Warman, 1972, pp. 229B232. NASA Document TM X­2440.  "

OT-15. Iron-55 and Iron-59 Metabolism in Humans

A STUDY WAS CONDUCTED in 1956 by medical researchers at the University of Washington, Seattle to determine the effects of red blood-cell destruction and altered body iron stores on the amount of iron turnover in plasma. Study subjects comprised 14 normal male subjects, 12 patients with nonhematologic diseases, and 59 patients with various hematological diseases.

Red blood cells from donors were stored at cold temperatures (4 degrees Celsius to increase cell destruction. Iron-59 (Fe⁵⁹), as ferric chloride or ferric citrate, was incubated with fresh plasma and administered intravenously to the subjects. Subjects received between 1 and 15 microcuries of Fe⁵⁹. Samples of blood were later drawn and analyzed for plasma Fe⁵⁹ activity. Unstated amounts of iron-55 were used in dual tracer experiments to determine clearance rates of iron administered in different ways.

The study showed that the plasma iron turnover is not affected by the rate of red cell destruction, and is affected, to a limited extent, by the increased body stores. This study provided new information on plasma iron turnover in both normal subjects and patients with hematological disorders. The research was supported by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995, and since revised)

References

Bothwell, T.H., A.V. Hurtado, D.M. Donohue, and C.A. Finch. AErythrokinetics. IV. The Plasma Iron Turnover as a Measure of Erythropoiesis.@Blood: The Journal of Hematology. Vol. 12, 1957, pp. 409B427.

Letter. C.A. Finch to S. Marks. July 17, 1984. Pacific Northwest Laboratory General Human Subjects, Box Alan Rither, PNL-9055-DEL (CIC #701610, bate 8756).  "

OT-16. Study of Blood Labeled with Chromium-51 in Normal Subjects

A STUDY WAS CONDUCTED in 1955 to1956 by medical scientists at the University of Washington using 19 normal subjects and 25 patients with anemia from the King County Hospital metabolic ward.

In this study, components of human blood from donors were labeled with chromium-51 (Cr⁵¹), phosphorus-32 (P³²), iron-55 (Fe⁵⁵), or iron-59 (Fe⁵⁹) and infused into the circulating blood of study subjects. Blood samples for radioactive analysis were drawn before injection and at 10, 30, 60, 90, 120, and 180 minutes and 12 hours after injection. Iron-59 was counted in a scintillation well-counter. When Fe⁵⁹ was employed to determine red cell utilization, P³² was used for the cell volume measurements. When Fe⁵⁵ was used, Cr⁵¹ was employed for the red cell mass determination. The amount of each isotope administered to subjects is not known.

This study led to a new way of characterizing red cell formation (erythropoiesis) and helped explain the variation found in normal subjects. The research was supported by grants from the U.S. Atomic Energy Commission and the State of Washington Initiative 171 funds for research in Biology and Medicine. (Included in The DOE Roadmap of February 1995, and since revised)

References

Gilblett, E.R., D.H. Coleman, G. Pirzio-Biroli, D.M. Donohue, A.G. Motulsky, and C.A. Finch. AErythrokinetics: Quantitative Measurements of Red Cell Production and Destruction in Normal Subjects and Patients with Anemia.@Blood: The Journal of Hematology. Vol. 11, Number 4, 1956, pp. 291B309.

Letter. C.B. Finch to S. Marks. July 17, 1984. Pacific Northwest Laboratory General Human Subjects, Box Alan Rither, PNL-9055-DEL (CIC #701610, bate 8756).  "

OT-17. Total-Body Neutron Activation Analysis

Between 1970 and 1973, studies on the potential usefulness of total-body neutron activation analysis as a diagnostic tool were conducted at University Hospital, University of Washington, Seattle.

In the first stage, 40 to 50 females were studied to develop the technique. All were over the age of 55 years and were afflicted with known bone­wasting diseases, such as osteoporosis. In the second stage, which used this new technique with subjects, 25 chronically ill adults suffering from kidney failure were studied to evaluate calcium balance. Females in the second stage were beyond childbearing years.

All subjects were exposed to uniform low­flux, high­energy neutrons. The total-body dose to study participants was estimated to be 2.1 rems. Initial subject were given a 1­year examination, but no longer­term follow­up was conducted. This study was funded by the U.S. Atomic Energy Commission and the Public Health Services. (Previously described in #38 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995, and since revised.)

References

Nelp, W.B., H.E. Palmer, R. Murano, K. Pailthorp, G.M. Hinn, C. Rich, J.I. Williams, T.G. Rudd, and J.D. Denney. AMeasurement of Total-Body Calcium (Bone Mass) In Vivo with the Use of Total-Body Neutron Activation Analysis.@Journal of Laboratory and Clinical Medicine, Vol. 76, 1970, pp. 151B162.

Letter. W.B. Nelp to S. Marks. August 30, 1984. Pacific Northwest Laboratory, General Human Subjects, Box Alan Rither, PNL 9055 DEL.  "

OT-18. Utah Strontium-85 Metabolism Study

THE UNIVERSITY OF UTAH Radiobiology Laboratory conducted a strontium­85 (Sr⁸⁵) metabolism study on subjects in 1956 to determine the uptake, retention, and excretion of Sr⁸⁵ in man. The study was conducted to learn more about the likely metabolism of strontium­90 (Sr⁹⁰) fallout from atomic testing.

Subjects consisted of seven male patients at the Salt Lake Veterans Administration Hospital and two male staff members. Five of the patients had normal bone metabolism and two had osteoporosis. After intravenous injection of approximately 5 microcuries of Sr⁸⁵, measurements were made over time to determine concentrations of Sr⁸⁵ in plasma, urine, and feces. Bone tissue biopsy samples obtained from two osteoporotic patients and from two normal subjects were analyzed for Sr⁸⁵ and calcium. In addition, several bone samples were obtained at autopsy from a tenth injected patient who was not bioassayed along with the other patients.

This work showed that strontium cleared more efficiently than calcium from the blood and was excreted primarily in urine rather than feces. This study was part of Project Sunshine and was supported by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995, and since revised)

References

Van Dilla, M.A., S. Wallach, and J.S. Arnold. ASr⁸⁵ Tracer Studies in Humans.@Semiannual Progress Report. Salt Lake City: Radiobiology Laboratory, University of Utah, September 30, 1956. "

OT-19. Radioisotope Studies at the Fernald State School, Massachusetts

IN THE EARLY TO MID-1950s, various radiation­related studies were carried out at the Fernald State School in Waverly, Massachusetts, using students as subjects. In a study addressing calcium metabolism, nine adolescent males, institutionalized for mental inadequacy but otherwise physically normal, ranging in age from 10 to 15 years, and one 21­year­old male participated as subjects.

The adolescents received 0.7 microcurie of calcium­45 (Ca⁴⁵). The subjects were divided into two groups: one group was administered the Ca⁴⁵ intravenously, the other received it orally. One month later, 0.74 microcurie was administered, but the means of administration was reversed between the groups. Two years later, 2.02 microcuries of Ca⁴⁵ were administered to the 21­year­old subject (who by then was 23). The studies showed that calcium is retained in the body for some time and that it is eventually excreted more through urine than feces.

A second study addressed thyroid function in Down=s syndrome subjects and their parents. Twenty­one male and female Down=s syndrome students ranging in age from 5 to 26 years participated, as did 5 female and 2 male normal parents of these students. The students were orally administered 70 microcuries of iodine­131 (I¹³¹). The parents received 100 microcuries. Thyroid uptake, turnover, and urinary excretion were subsequently measured. Additionally, thyroxine metabolism was studied in two Down=s syndrome students after intravenous injection of 55 microcuries of thyroxine labeled with I¹³¹.

These studies showed that iodine uptake was in the low­normal range and did not differ significantly from normal values; that the iodine turnover rate was significantly faster than normal; that the thyroxine turnover rate was normal; and that the uptake, turnover, and excretion rates in parents of Down=s syndrome children were normal. These studies were supported in part by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

Bronner, F., R.S. Harris, C.J. Maletskos, and C.E. Benda. AStudies in Calcium Metabolism. The Fate of Intravenously Injected Radiocalcium in Human Beings.@Journal of Clinical Investigation. Vol. 35, 1956, pp. 78B88.

Kurland, G.S., J. Fishman, M.W. Hamolsky, and A.S. Freedberg. ARadioisotope Study of Thyroid Function in 21 Mongoloid Subjects Including Observations in 7 Parents.@Journal of Endocrinology and Metabolism. Vol. 17, 1957, pp. 552B560. "

OT-20. Uptake of Iodine-131 by Premature Infants in Detroit

IN 1954, the Pediatric Division and the Radioisotope Laboratory of Harper Hospital in Detroit, Michigan, studied the uptake of iodine­131 (I¹³¹) by the thyroid gland of premature infants. Sixty­five premature infants ranging in birth weight from 2.1 to 5.5 pounds were included in the study; seven full­term infants were used for the control group.

The premature infants were given 5 microcuries of I¹³¹ orally. Iodine-131 concentrations were then measured in the thyroid gland. It was found that the range of uptake of I¹³¹ in this series of infants was within the limits of normal as measured in studies of full­term children and adults. (Previously described in #4 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Martmer, E.E., K.E. Corrigan, H.P. Charbeneau, and A. Sosin. AA Study of the Uptake of Iodine (I¹³¹) by the Thyroid of Premature Infants.@AMA American Journal of Diseases of Children. Vol. 17, 1955, pp. 503B509.  "

OT-21. Testicular Irradiation of Oregon State Prison Inmates

FROM AUGUST 1963 to May 1971, the Pacific Northwest Research Foundation in Seattle, Washington, conducted studies on the effects of radiation on human testicular function using as subjects inmates at the Oregon State Prison in Salem. The purpose of the study was to determine the effects of ionizing radiation on sperm production and to determine minimum dose levels for initial effect and permanent damage.

Sixty­seven healthy volunteers ranging in age from 24 to 52 years were irradiated by x­rays at least once during the course of the study. Of these 67 subjects, 6 received a second irradiation, 1 received 3 irradiations, and 1 received a series of 11 weekly irradiations. Testicular absorbed doses ranged from 8 to 640 rads. Postirradiation studies included analysis of blood, urine, and seminal fluid, and biopsy of sperm­producing tissues.

Subjects were compensated for their participation and for each biopsy. All subjects who had not been previously vasectomized agreed to undergo a vasectomy at the conclusion of the study. All did so and received additional compensation for the procedure.

All subjects were volunteers and could withdraw from participation at any time. The study was reviewed at 3­month intervals by a review board and three additional reviews were provided by a national ad hoc committee.

This study showed that a single testicular dose of 600 rads caused temporary disruption of testicular function. Recovery time was dose dependent; the higher the dose, the longer the time required for recovery. Subjects who were irradiated a second or third time had responses that were similar to their initial responses. This work was supported by the U.S. Atomic Energy Commission. (This experiment was referenced in the Markey report and included in The DOE Roadmap of February 1995.)

References

Heller, C.G. Effects of Ionizing Radiation on the Testicular Function of Man: 9 Year Progress Report. Seattle: Pacific Northwest Research Foundation, May 1972.

Heller, C.G., D.E. DiIaconi, and M.J. Rowley. Protection of the Rights and Welfare of Prison Volunteers: Policies Followed Throughout a 17­Year Medical Research Program. Seattle: Pacific Northwest Research Foundation.

Rowley, M.J., D.R. Leach, G.A. Warner, and C.G. Heller. AEffect of Graded Doses of Ionizing Radiation on the Human Testis.@Radiation Research. Vol. 59, 1974, pp. 665B678.

ABackground Information on AEC Human Testicular Irradiation Projects in Oregon and Washington State Prisons.@Information from ERDA. Washington, DC: U.S. Energy Research and Development Administration, March 1975.  "

OT-22. Distribution of Zinc-65 in Blood and Organs of Humans

IN 1947, RESEARCHERS in Boston administered zinc­65 (Zn⁶⁵) to a 67­year­old male suffering from myelogenous leukemia and to a nonleukemic, healthy subject. The purpose of this study was to determine how the content and distribution of zinc in blood and organs of the normal subject compared with the zinc content and distribution in the leukemia patient.

Zinc-65 was injected intravenously as zinc chloride daily for several days and in amounts ranging from 2 milligrams per day to Afar in excess of this amount.@Analysis occurred over a long period of time to monitor Zn⁶⁵ retention.

This experiment showed that zinc plays an important role in the metabolism of tissues and blood cells. The work was supported by the U.S. Atomic Energy Commission. (Previously described in #32 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Gibson, J.G., B.I. Vallee, R.G. Fluharty, and J.E. Nelson. Studies of the Zinc Content of the Leucocytes in Myelogenous Leukemia. Oak Ridge, TN: Oak Ridge Operations Office, 1947. (RHTG) Classified Docs 1944B1994, Records Holding Area-Bldg 2714-H Vault, Box RHA H108-5, 1 of 2, Folder AAdvisory Committee.@

Vallee, B.L., R.G. Fluharty, and J.G. Gibson. Distribution of Zinc in Normal Blood and Organs Studied by Means of Zn⁶⁵. Oak Ridge, TN: Oak Ridge Operations Office, 1947. (RHTG) Classified Docs 1944B1994, Records Holding Area­Bldg 2714­H Vault, Box RHA H108­5, 1 of 2, Folder AAdvisory Committee.@   "

 ‡  ‡  ‡

OT-23. Thyroid Uptake and Urinary Excretion of Iodine-131 in Assessing Thyroid Function

IN THE 1950s, physicians in the Pediatric Department, University of Arkansas School of Medicine in Little Rock evaluated the use of measurements of iodine-131 (I¹³¹) uptake by the thyroid and its excretion in urine as a means of assessing thyroid function in children. The study included 30 children, 25 with normal thyroid function (euthyroid), and 5 born either without a thyroid or with a thyroid that was virtually nonfunctional (congenital hypothyroidism). The euthyroid subjects consisted of 14 males and 11 females between the ages of 9 months and 15 years, of whom 11 were white and 14 were nonwhite.

Five microcuries of I¹³¹ with stable potassium iodide carrier were administered orally to subjects up to 6 years of age. Ten microcuries were administered to subjects, ages 7 to 15 years. The hypothyroid subjects also were given 65 milligrams of thyroid extract daily for an unreported period of time. Measurements of I¹³¹ activity in the thyroid were made and urine samples were obtained from the normal subjects 2, 4, 6, 48, 72, and 96 hours after administration. Similar measurements were obtained frequently from the hypothyroid subjects during and after administration of thyroid extract.

Thyroid uptake of I¹³¹ was between 9 and 30 percent in the normal children, while the hypothyroid children absorbed between zero and 2.2 percent of the administered I¹³¹. The rate of I¹³¹ excretion was much higher in hypothyroid children than in the normal controls. The researchers concluded that this method was reliable for assessing thyroid function. This study was approved by and appears to have been supported by the U.S. Atomic Energy Commission. 

References

Reilly, W.A., and D. Bayer. AThe Value of the Measurements of Thyroid Uptake and Urinary Excretion of I¹³¹ in Assessing Thyroid Function of Normal and Congenitally Hypothyroid Children.@Journal of Pediatrics. Vol. 40, JanuaryBJune 1952, pp. 714B721.  "

OT-24. Short-Term Clearance Studies Using Iodine-131

DURING THE EARLY 1960s, researchers at the University of Arkansas Medical Center in Little Rock conducted studies on the accumulation of iodine-131( I¹³¹) in the thyroid and elimination of iodine from subjects. In all, 40 healthy subjects participated. Each subject was injected with 10 microcuries of I¹³¹. Measurements were made at various intervals of I131 activity in the thyroid and with samples of urine, plasma, and feces.

This study showed that the clearance of I¹³¹ through the kidneys decreased at night by a factor of 1.4 when compared to daytime clearance, while the clearance of I¹³¹ through the thyroid gland remained approximately constant over 24-hour periods. This information, together with other data on the loss of iodine through sweat, feces, and urine, improved the scientists=understanding of the metabolism of stable iodine in the body. This work was supported by the National Institutes of Health and the U.S. Atomic Energy Commission.

References

Oddie, T.H., D.A. Fisher, and J.M. Long. AFactors Affecting the Estimation of Iodine Entering the Normal Thyroid Gland Using Short-Term Clearance Studies.@Journal of Clinical Endocrinology. Vol. 24, 1964, pp. 924B933.  "

OT-25. Study of Iodine-131-Thyroxine Metabolism in Adolescent and Adult Human Subjects

A STUDY WAS CONDUCTED during 1961 to 1964 at the University of Arkansas Medical Center in Little Rock on the metabolism of iodine-131 (I¹³¹)Blabeled thyroxine in 24 euthyroid (normal thyroid function) subjects. The purpose of this study was to measure the absorption and degradation rate of thyroxine in euthyroid subjects. The subjects ranged in age from 13 to 51 years. The adolescent subjects in the study were wards of the Arkansas Children=s Colony and were physically normal with mild to moderate mental retardation. The adult participants were normal, healthy volunteers.

The subjects were administered thyroxine labeled with tracer amounts (about 15 microcuries) of I¹³¹ either by intravenous injection or orally. Radioiodine was measured by external counting of the subject=s thyroid, by whole-body counting to determine extrathyroid thyroxine, and by analyzing fecal specimens.

Results of this study showed that 73 percent of orally administered thyroxine was absorbed, and that about 12 percent of the extrathyroid fraction of systemic thyroxine was excreted from the body per day. Iodine-131Blabeled hormone was administered to evaluate the comparability of noninvasive in vivo (whole-body and thyroid) counting with the established invasive method. This method also involved administration of I¹³¹-labeled thyroxine, but required the drawing of serial blood samples for plasma counting to evaluate thyroxine metabolism as a measure of thyroid function.

The investigators found that not only did the in vivo method give similar results to the plasma counting method, but it also required a smaller amount of I¹³¹-labeled hormone and was more acceptable to the subject, thereby enabling measurements to be made more frequently or over a longer period of time. This work was supported by grants from the National Institutes of Health and the U.S. Atomic Energy Commission.

References

Oddie, T.H., D.A. Fisher, and C. Rogers. AWhole-Body Counting of I¹³¹-Labeled Thyroxine.@Journal of Clinical Endocrinology. Vol. 24, 1964, pp. 628B637.  "

OT-26. Study of Iodine-131BTriiodothyronine Counting in Normal Subjects

A STUDY WAS CONDUCTED during the period 1961 to 1964 at the University of Arkansas Medical Center in Little Rock on the metabolism of iodine-131 (I¹³¹)Blabeled triiodothyronine (T₃) in 18 healthy, adult volunteers with normal thyroid (euthyroid) function. The purpose of this study was to measure the absorption and degradation rate of triiodothyronine in subjects with normal thyroid function, and to develop noninvasive, whole-body counting techniques for this measurement.

The subjects were administered about 5 to 15 microcuries I¹³¹-labeled thyroxine or triiodothyronine, either intravenously or orally. Radioiodine was measured by external counting of the subject=s thyroid, by whole-body counting to determine extrathyroid hormone, and by analyzing fecal specimens.

Results of this study showed that T₃ is more rapidly excreted and degraded than thyroxine (T₄). Approximately 53 percent of extrathyroidal T₃ was degraded per day after intravenous administration. Approximately 85 percent of orally administered T₃ was absorbed. This study provided further explanation for observed T₄/T₃ ratios in plasma. This work was supported by grants from the National Institutes of Health and the U.S. Atomic Energy Commission.

References

Fisher, D.A., and T.H. Oddie. AWhole-Body Counting of I¹³¹-Labeled Triiodothyronine.@Journal of Clinical Endocrinology. Vol. 24, 1964, pp. 733B739.  "

OT-27. Thyroid Hormone Secretion Studies Using Iodine-131

FROM 1963 TO 1964, the University of Arkansas Medical Center in Little Rock conducted studies in humans on iodine accumulation in the thyroid gland, iodine metabolism, and secretion of thyroxine hormone. In all, 152 subjects (including both men and women) ranging in age from 10 to 61 years and having normal thyroid function, participated. These subjects included volunteer hospital employees, students, and patients, as well as moderately mentally retarded children and young adult volunteers from the Arkansas Children=s Colony.

Thyroid gland accumulation of iodine was measured in all subjects. Ten microcuries of iodine-131 (I¹³¹) were injected intravenously into each subject to measure iodine uptake, retention, and clearance from the thyroid and urinary iodine excretion by the kidneys. In 29 subjects, the uptake of I¹³¹-labeled thyroxine was measured by whole-body counting and compared with stable iodine accumulation.

These studies showed that thyroidal iodine increased progressively with increasing iodine uptake, while thyroxine secretion remained constant. This work was supported by the Institute of Arthritis and Metabolic Diseases, the U.S. Public Health Service, and the U.S. Atomic Energy Commission.

References

Fisher, D.A., and T.H. Oddie. AComparison of Thyroidal Iodide Accumulation and Thyroxine Secretion in Euthyroid Subjects.@Journal of Clinical Endocrinology. Vol. 24, 1964, pp. 1,143B1,154.

Oddie, T.H., D.A. Fisher, and J.M. Long. AFactors Affecting the Estimation of Iodine Entering the Normal Thyroid Gland Using Short-Term Clearance Studies.@Journal of Clinical Endocrinology. Vol. 24, 1964, pp. 924B933.  "

OT-28. Brain Scanning Studies Using Potassium-42

DURING THE LATE 1940s, researchers at the Neurosurgical and Surgical Services and Laboratories of Harvard Medical School, Children=s Hospital, and Peter Bent Brigham Hospital in Boston, Massachusetts, conducted collaborative studies on brain tumor localization, using potassium-42 (K⁴²). A total of 15 normal, healthy volunteers (12 males and 3 females in their twenties) and 39 patients with known or suspected brain tumors, including 15 males and 22 females between the ages of 3 months and 66 years, participated as subjects. Adult subjects were administered 10 to 15 microcuries of K⁴² by intravenous injection. Subjects under 16 years of age were administered 2 to 3 microcuries of K⁴². Activity in the brain was measured with an external counter.

The results of these studies showed that K⁴² was of limited value as a brain tumor scanning agent. Potassium is readily taken up by tumor tissue, but is taken up more rapidly by blood and muscle tissueCa difference which can cause a masking effect for tumor scanning. This work was supported by the American Cancer Society and the U.S. Atomic Energy Commission.

References

Susen, A.F., W.T. Small, and F.D. Moore. AStudies on the External Diagnostic Localization of Brain Lesions Using Radioactive Potassium.@In Surgical Forum Proceedings of the Forum Sessions, Thirty-Sixth Clinical Congress of the American College of Surgeons, Boston, MA, October 1950, pp. 362B368.  "

OT-29. Studies on Body Potassium Using Potassium-42

DURING THE LATE 1940s, researchers at Harvard Medical School and Peter Bent Brigham Hospital, Boston, Massachusetts, conducted studies on exchangeable potassium levels in humans using potassium-42 (K⁴²). The term Aexchangeable@refers to that portion of total-body volume that is not stored in tissues.

Thirty healthy males, ranging in age from 21 to 32 years, participated as subjects. Each was administered about 100 microcuries of K⁴² by intravenous injection and activity was measured in urine samples collected over the next 40 hours. Blood samples from 16 of the subjects were also analyzed for activity.

The studies showed that exchangeable potassium accounts for approximately 95 percent of total-body potassium. This work was supported by the U.S. Atomic Energy Commission.

References

Cosra, L., Jr., J.M. Olney, Jr., R.W. Steenburg, M.R. Ball, and F.D. Moore. AThe Measurement of Exchangeable Potassium in Man by Isotope Dilution.@The Journal of Clinical Investigation. Vol. 29, 1950, pp. 1,280B1,295.  "

OT-30. Serum Level of Protein Bound Iodine-131 in the Diagnosis of Hyperthyroidism

DURING THE LATE 1940s, scientists at the Medical Research Laboratories, Beth Israel Hospital, and the Department of Medicine, Harvard Medical School, Boston, Massachusetts, evaluated the effectiveness of iodine-131 (I¹³¹) as a tool for diagnosis of hyperthyroidism. A total of 20 patientsC10 with thyrotoxicosis (hyperthyroidism) and 10 normal controlsCbetween 10 and 65 years of age, participated as subjects.

Sixteen of the 20 patients were female. Each subject received 150 microcuries of carrier-free I¹³¹ orally. Twenty-four hours after administration of the I¹³¹, 10 milliliters of blood were drawn and measured for serum-protein bound I¹³¹. It was found that the hyperthyroid patients had much higher levels of I¹³¹ in their serum protein than the normal controls.

The researchers concluded that I¹³¹ was a valuable diagnostic tool for investigating hyperthyroidism. This study was funded by the President and Fellows of Harvard College, the Office of Naval Research, and the U.S. Atomic Energy Commission.

References

Freedburg, A., A. Urelis, and S. Hertz. ASerum Level of Protein Bound Radioactive Iodine (I¹³¹) in the Diagnosis of Hyperthyroidism.@In Proceedings of the Society for Experimental Biology and Medicine. Vol. 70, No. 4, April 1949, pp. 679B682.  "

OT-31. Body Constituent Studies Using Sodium-24 and Potassium-42

BETWEEN 1946 AND 1951, researchers at Harvard Medical School and Peter Bent Brigham Hospital, Boston, Massachusetts, conducted studies of exchangeable sodium and potassium in humans using sodium-24 (Na²⁴) and potassium-42 (K⁴²). The term Aexchangeable@refers to that portion of total-body volume that is not stored in tissues.

Fourteen normal young adults, both men and women, were administered Na²⁴, and 47 similar subjects were administered K⁴². Amounts of body sodium and potassium were then calculated using standard dilution methods. One of the subjects had participated in a pilot study in 1946 and the earlier data were correlated with data from the present study.

These studies provided new information on sodium and potassium levels in both males and females, and indicated that the plasma was the best body fluid in which to measure this exchange. This work was supported by the U.S. Atomic Energy Commission.

References

Edelman, I.S., J.M. Olney, A.H. James, L. Brooks, and F.D. Moore. ABody Composition: Studies in the Human Being by the Dilution Principle.@Science. Vol. 115, April 25, 1952, pp. 447B454.

Moore, F.D. ADetermination of Total-Body Water and Solids with Isotopes.@Science. Vol. 104, August 16, 1946, pp. 157B160.  "

OT-32. Red Blood-Cell Volume Studies Using Chromium­51

IN 1949 AND 1950, scientists at the Biophysical Laboratory and the Department of Medicine of Harvard Medical School and the Medical Clinic at the Peter Bent Brigham Hospital, Boston, Massachusetts, conducted studies to determine red blood-cell volume using chromium­51 (Cr⁵¹). Twenty-five healthy male volunteers participated as subjects.

A 50-milliliter blood sample was drawn from each subject, and the red cells were labeled with 40 to 200 microcuries of Cr⁵¹ as sodium chromate. After standing 1 hour at room temperature, the labeled blood sample was reinjected intravenously into the corresponding donor subject. Red blood-cell samples were obtained 10 minutes after injection and at three 10­minute intervals thereafter, and were measured for Cr⁵¹ activity. Blood volume was calculated using this information. The accuracy of this method was confirmed in five other hospitalized patients: three males ages 30, 36, and 38 years with cirrhosis of the liver or bronchiogenic cancer, and two females ages 53 and 69 years, with polycythemia vera. These subjects were given a second injection of Cr⁵¹­labeled red cells after transfusion or recent hemorrhage of a known volume of red cells.

The study showed that Cr⁵¹ labeling was an effective tool in measuring red blood-cell volume. This work was supported in part by the Office of Naval Research, National Cancer Institute, and the U.S. Atomic Energy Commission.

References

Sterling, K., and S.J. Gray. ADetermination of the Circulating Red Cell Volume in Man by Radioactive Chromium.@Journal of Clinical Investigation. Vol. 29, 1950, pp. 1,614B1,619.  "

OT-33. Studies on Body Sodium Using Sodium-24

DURING THE EARLY 1950s, researchers at the Harvard Medical School and Peter Bent Brigham Hospital, Boston, Massachusetts, conducted studies on exchangeable sodium levels in humans using sodium-24 (Na²⁴). Exchangeable sodium is that which is not stored in body tissue.

Twenty-seven healthy males or females, ranging in age from 22 to 61 years, participated as subjects. Between 100 and 200 microcuries of Na²⁴ were administered to each subject by intravenous injection and the radioactivity was measured in blood and urine samples collected over the next 48 hours.

These studies showed that equilibrium in the body was reached 15 to 24 hours after injection and that total exchangeable sodium for both men and women is about 0.96 gram per kilogram of body weight. They also showed that Na²⁴ was a convenient and accurate tool for estimating the exchangeable sodium content of the body. This work was supported by the Upjohn Company, Winthrop-Stearns, Inc., and the U.S. Atomic Energy Commission.

References

Edelman, I.S., A.H. James, L. Brooks, and F.D. Moore. ABody Sodium and Potassium IV. The Normal Total Exchangeable Sodium; Its Measurement and Magnitude.@Metabolism. Vol. 3, 1954, pp. 530B538.  "

OT-34. Bone Studies Using Sodium-24

DURING THE EARLY 1950s, researchers at Harvard Medical School and Peter Bent Brigham Hospital, Boston, Massachusetts, conducted studies of bone composition and sodium penetration using sodium-24 (Na²⁴). The subject was intravenously administered 100 microcuries of Na²⁴. A segment of rib and a blood sample were obtained and analyzed 26 hours after injection.

These studies provided data on human bone composition and indicated that about 45 percent of bone sodium was exchangeable in 4 hours. This work was supported by the American Heart Association, the Upjohn Company, Winthrop-Stearns, Inc., and the U.S. Atomic Energy Commission.

References

Edelman, I.S., A.H. James, H. Baden, and F.D. Moore. AElectrolyte Composition of Bone and the Penetration of Radiosodium and Deuterium Oxide Into Dog and Human Bone.@The Journal of Clinical Investigation. Vol. 33, February 1954, pp. 122B131.  "

OT-35. Studies of Calcium Metabolism and Thyroid Disease Using Calcium-45

DURING THE EARLY 1950s, researchers at Harvard Medical School, Boston, Massachusetts, conducted studies on the effect of thyroid disease on calcium metabolism in humans. Study participants included 11 patients, both male and female (with diagnoses of hyperthyroidism, myxedema, hypothyroidism, Paget=s disease, and euthyroidism), at Massachusetts General Hospital in Boston, who ranged in age from 19 to 67 years.

Subjects received an intravenous injection of 5 to 7 microcuries of calcium-45 (Ca⁴⁵). After injection, samples of blood, urine, and feces were obtained over various time intervals and analyzed for Ca⁴⁵ content.

The study indicated that bone formation and destruction occurred at increased rates in patients with thyroid disease. This work was supported by the U.S. Atomic Energy Commission.

References

Krane, S.M., G.L. Brownell, J.B. Stanbury, and H. Corrigan. AThe Effect of Thyroid Disease on Calcium Metabolism in Man.@Journal of Clinical Investigation. Vol. 35, 1956, pp. 874B887.  "

OT-36. Analysis of Red Blood-Cell Survival in the Body Using Chromium-51

DURING 1950 TO 1953, researchers at Massachusetts Memorial Hospitals and the Boston University School of Medicine conducted studies on chromium-51 (Cr⁵¹)Blabeling for red blood cells to determine the survival times of red blood cells in the body.

In the first experiment, donor blood was collected and tagged with Cr⁵¹ as sodium chromate, and injected into nine normal, healthy medical students. Approximately 500 milliliters of blood was drawn from each subject immediately prior to transfusion. In the second experiment, 10 hospitalized patients without hematologic abnormalities or other blood diseases received 50 milliliters blood tagged with Cr⁵¹ at weekly intervals. The amount of Cr⁵¹-labeled red blood cells in circulating blood was then determined at various times after injection in each of the patients. The percent of donor cells surviving were determined for each time point. The excretion of Cr⁵¹ in subjects=urine was also determined.

This study showed that red blood cells rapidly combine with Cr⁵¹ in circulation and that the method is useful for determining red blood-cell survival times. This work also provided a simple, new method for evaluating the preservation of red blood cells. This work was supported by the American Cancer Society of Massachusetts, Inc., and the U.S. Atomic Energy Commission.

References

Ebaugh, F.G., Jr., C.P. Emerson, and J.F. Ross. AThe Use of Radioactive Chromium-51 as an Erythrocyte Tagging Agent for the Determination of Red Cell Survival In Vivo.@Journal of Clinical Investigation. Vol. 32, 1953, pp. 1,260B1,276.  "

OT-37. Blood Volume Studies Using Chromium-51

BETWEEN 1952 AND 1953, researchers at Harvard Medical School and the Peter Bent Brigham Hospital, Boston, Massachusetts, conducted studies on blood volume determination using chromium-51 (Cr⁵¹). Nine normal males ranging in age from 23 to 57 years and 14 surgical patients ranging in age from 17 to 72 years participated as subjects.

Between 75 and 100 microcuries of Cr⁵¹ were administered as sodium chromate by intravenous injection to each subject. Activity was measured in blood samples drawn 20 to 40 minutes after injection and, in five cases, up to 100 days after injection. Eleven subjects participated in two separate studies.

The results of these studies showed that the radiochromium method was a valid, simplified procedure for blood volume measurement. This work was supported by the U.S. Atomic Energy Commission.

References

Read, R.C. AStudies of Red Cell Volume and Turnover Using Radiochromium.@The New England Journal of Medicine. Vol. 250, No. 24, June 17, 1954, pp. 1,021B1,027.  "

OT-38. Studies of Stable Iodine Uptake Using Iodine-131 as a Tracer

IN 1952 AND 1953, researchers in the Radioisotope Unit at Boston Veterans Administration Hospital, the Massachusetts Memorial Hospitals, and the Department of Medicine at Boston University School of Medicine conducted studies of the uptake of iodine among three groups of patients that differed with respect to thyroid status. The purpose of these studies was to learn more about factors influencing the uptake of stable iodine in humans. Most of the 197 patients who served as study subjects had been referred for evaluation of possible thyroid disease. Of the 197, 85 either had tested negative for thyroid disease and were considered Anormal@with respect to thyroid function (euthyroid) or had thyroid disease that remained untreated. The remaining 112 subjects had abnormally active thyroids (hyperthyroid) for which they had been treated previously (but not during the 3 months immediately prior to the study) with antithyroid drugs, radioiodine or surgery.

Iodine-131 (I¹³¹), usually 50 microcuries, was administered as a tracer to each subject by intravenous injection 2 to 3 hours following breakfast. Blood samples were drawn at the time of monitoring to determine the serum protein-bound iodine concentrations. Urine samples were also collected from the subjects for I¹³¹ analysis.

The study showed a correlation between I¹³¹ uptake by the thyroid and serum protein-bound iodine concentration. Stable iodine uptake values associated with each protein-bound iodine level showed greater variation among the treated group than among the normal or untreated group. This study was supported by the U.S. Atomic Energy Commission.

References

Burrows, B.A., and J.F. Ross. AThe Thyroidal Uptake of Stable Iodine Compared to the Serum Concentration of Protein-Bound Iodine in Normal Subjects and in Patients with Thyroid Disease.@Journal of Clinical Endocrinology and Metabolism. Vol. 13, 1953, pp. 1,358B1,368.  "

OT-39. Studies of Iron Metabolism, Anemia, and Cancer Using Iron-59 and Chromium-51

DURING THE MID-1950s, researchers at the Massachusetts Memorial Hospitals, Boston Veterans=Administration Hospital, and the Boston University School of Medicine conducted studies of the iron metabolism and causes of anemia in cancer patients, using iron-59 (Fe⁵⁹) and chromium-51 (Cr⁵¹).

Thirty-eight cancer patients participated as subjects. Plasma was obtained from normal subjects, mixed with approximately 10 microcuries of Fe⁵⁹ as ferric ammonium citrate, and intravenously administered to each patient. Iron-59 disappearance from plasma, plasma iron turnover, red cell utilization of Fe⁵⁹, red cell turnover, red cell iron renewal rate, and Fe⁵⁹ localization were subsequently measured. Two patients also participated in a red cell survival study, which included administration of Cr⁵¹ and activity measurement in blood samples for 5 weeks.

These studies showed increased red cell destruction in the cancer patients and increased red cell production, which was insufficient to prevent anemia resulting from the red cell destruction. This work was supported by the U.S. Atomic Energy Commission.

References

Miller, A., R.B. Chodos, C.P. Emerson, and J.F. Ross. AStudies of the Anemia and Iron Metabolism in Cancer.@Journal of Clinical Investigation. Vol. 35, 1956, pp. 1,248B1,262.  "

OT-40. Studies of Iron Metabolism, Anemia, and Rheumatoid Arthritis Using Iron-59

DURING THE MID-1950s, researchers at the Massachusetts Memorial Hospitals, Robert Breck Brigham Hospital, Boston University School of Medicine, and Harvard Medical School conducted studies of iron metabolism and anemia in patients with rheumatoid arthritis using iron-59 (Fe⁵⁹). Forty-two male or female patients ranging in age from 20 to 71 years, and 10 male or female controls (healthy volunteers) ranging in age from 30 to 65 years participated as subjects.

Plasma drawn from normal donors was mixed with Fe⁵⁹ as ferric ammonium citrate and intravenously administered to each subject. The administered activity was approximately 5 to 10 microcuries. Plasma Fe⁵⁹ removal rate, red cell uptake, serum iron concentration, red cell survival rate, red cell volume, plasma volume, and total blood volume were subsequently measured.

These studies showed that rheumatoid arthritis patients had normal utilization of plasma iron for red cell production, increased red cell destruction, and increased but insufficient red cell production. This work was supported by the U.S. Atomic Energy Commission.

References

Freireich, E.J., J.F. Ross, T.B. Bayles, C.P. Emerson, S.C. Finch, and C. MacDonald. ARadioactive Iron Metabolism and Erythrocyte Survival Studies of the Mechanism of the Anemia Associated with Rheumatoid Arthritis.@Journal of Clinical Investigation. Vol. 36, 1957, pp. 1,043B1,058.  "

OT-41. Iron Absorption Studies Using Iron-59

DURING THE MID-1950s, researchers at the Boston Veterans Administration Hospital, Boston University School of Medicine, Harvard Medical School, and Tufts University School of Medicine conducted studies of the absorption of dietary iron using iron-59 (Fe⁵⁹). Thirty-two male patients with normal blood iron values, 15 patients with chronic blood loss, and 9 patients with idiopathic hemochromatosis (a disease characterized by excessive iron intake for unknown reasons) participated as subjects.

Red blood-cell indices were determined for each subject using a standard phosphorus-32 (P³²) labeling technique. The 56 subjects participated in a total of 84 individual studies involving the oral administration of 12 to 50 microcuries of Fe⁵⁹ as ferric or ferrous chloride or the ingestion of 7 to 23 microcuries of Fe⁵⁹ in labeled eggs or vegetables. Activity levels were measured in subsequently collected blood and stool samples.

These studies showed that iron administered as a chloride salt was more readily absorbed than dietary iron and that dietary iron was not absorbed in sufficient amounts to overcome increased loss or to respond to increased requirements. This work was supported by the U.S. Atomic Energy Commission.

References

Chodos, R.B., J.F. Ross, L. Apt, M. Pollycove, and J.A.E. Halkett. AThe Absorption of Radioiron Labeled Foods and Iron Salts in Normal and Iron-deficient Subjects and in Idiopathic Hemochromatosis.@Journal of Clinical Investigation. Vol. 36, 1957, pp. 314B326.

Halkett, J.A.E., R.B. Chodos, and J.F. Ross. AThe Labeling of Human Foods with Radioactive Iron (Fe⁵⁹).@Journal of Laboratory and Clinical Medicine. Vol. 53, JanuaryBJune 1959, pp. 816B823.  "

OT-42. The Effects of Whole-Body Radiation on Organ Transplant Survival

EXPERIMENTS WERE CONDUCTED at Harvard Medical School, Boston, Massachusetts, in the early 1960s to determine whether total-body radiation with x­rays (250 to 650 rads) would suppress the natural rejection of organs and improve the success of organ transplantation. These studies were initiated after reports by French scientists that whole-body radiation might be helpful in suppressing the immune rejection response.

At least eight transplant recipients were known to have been involved in this study. These included six patients who received kidneys from identical twin donors. One patient was reported to be doing well 17 months after transplant. Additional radiation was prescribed to suppress the rejection response. Specific details on the survival times of transplant recipients and cause of death were not given, and some of the documentation is illegible. One patient, given 650 rads of x­ray radiation, accepted the kidney transplant, but died 28 days postirradiation. The death was ascribed to total-body radiation.

The study was terminated after it was determined that the deleterious effects of whole-body radiation were greater than their beneficial effects in suppressing the rejection of transplanted tissues. This work was supported by the U.S. Atomic Energy Commission.

References

Moore, F.D. AA Program for the Study of Transplantation of Bone Marrow, Tissues, and Whole Organs and of Related Topics in Surgical Research.@Progress Report and Outline of Renewal for Continuing Work. Boston: Harvard University, Harvard Medical School. AEC Number AT (30-1)-2265, June 1960.

Moore, F.D. ADiscussion Comments.@Annals of Surgery. Vol. 152, 1960, p. 372.

Factsheet. Human Experimentation-05 (SFS11.001) Project Name: Study of Transplantation of Bone Marrow Tissue and Whole Organs, etc., Department of Energy, Markey Files.

[illegible] project planning documents submitted by Dr. F.D. Moore, Moseley Professor of Surgery, Harvard Medical School, dated June 1960, for project TID 6107.  "

OT-43. Blood-Cell Studies in Colorado Prisoners Using Iron-59, Phosphorus-32, and Chromium-51

A SERIES OF STUDIES were conducted between 1960 and 1968 by investigators at the University of Colorado Medical Center, Denver to determine rates of red blood-cell regeneration and hemoglobin recovery after excessive blood loss; and to determine the survival rates and characteristics of red cells formed during periods of rapid cell development and severe iron deficiency. The subjects were male prisoners from the Colorado State Penitentiary in Canon City, and local county jails in the Denver area, who had volunteered to be study subjects.

The subjects were phlebotomized (bled) regularly until a condition of iron deficiency was reached. The subjects were then administered about 5 millicuries of iron-59 and 0.2 or 0.4 millicurie of phosphorus-32 as diisopropylfluorophosphate to label newly formed blood-cells in circulation. Samples of the blood were then obtained at various times after injection and were counted to determine the isotope content or were autoradiographed to determine their histological characteristics and other parameters, such as rate of red cell formation. It appears that other studies were conducted using chromium-51 to determine red cell survival times.

According to one of the investigators, the results of most of these studies were not published in the open scientific literature at the request of the University of Colorado administration. The funding sources for these studies have not been identified, though the principal investigator had previously served as a Manhattan Project physician at Billings Hospital in Chicago and had close affiliations with the U.S. Atomic Energy Commission during his career.

References

Block, M.H. Text-Atlas of Hematology. p. 36. Philadelphia: Lea & Febiger, 1976.

Hamstra, R.D., and M.H. Block. AErythropoiesis in Response to Blood Loss in Man.@Journal of Applied Physiology. Vol. 27, No. 4, October 1969, pp. 503B507.

Letter. M. Block to J.H. Lawrence. April 10, 1969. OHRE document number 715159.

Letter. D. Hamil to M. Block (date illegible), (University of Colorado Health Science Center).

Letter. R. Golden to J.E. Boyer. September 13, 1963, (University of Colorado Health Science Center).

Personal communication. J. Franks to D.R. Fisher. May 24, 1995.   "

OT-44. Tracer Studies of Arsenic Metabolism Using Arsenic-71 and Arsenic-74

IN APPROXIMATELY 1939 TO 1941, studies were conducted at the Massachusetts Institute of Technology (MIT) in collaboration with Massachusetts General Hospital and Harvard Medical School, Boston on the metabolism of arsenic in normal subjects and in hospital patients with leukemia. Small amounts of arsenic had previously been used in treatment of chronic myeloid leukemia. The purpose of this study was to evaluate the metabolism of arsenic using arsenic-71 (As⁷¹) and arsenic-74 (As⁷⁴)produced at the MIT cyclotron.

After preliminary studies in rats, guinea pigs, and rabbits, two healthy human subjects were given As⁷¹ and As⁷ as potassium arsenite with a stable arsenic carrier (1.5 milligrams) by subcutaneous injection. Administered activities varied from 15 to 25 millicuries As⁷¹ or 2 to 3 millicuries As⁷⁴. Amounts of arsenic excreted in urine and stool samples were then determined at various times, postinjection. It was found that almost all of the arsenic was excreted in urine. Higher specific activity levels of As⁷¹ and As⁷⁴ were administered to four leukemia patients to determine the rate of clearance of arsenic from blood. Bone marrow biopsies were obtained from two of the leukemia patients and spinal fluid was obtained from two patients to determine arsenic concentrations present.

One patient died of leukemia 4 days after injection and this provided an opportunity to measure arsenic concentrations in the patient=s liver, spleen, kidney, lungs, marrow, skeletal muscles, and other soft tissues. The greatest arsenic concentrations were found in muscle tissue and other rapidly growing tissue. This work was supported by various sponsors, including the John and Mary R. Markle Foundation and the H.N.C. Gift of the Harvard Medical School. The MIT Radioactivity Center was supported in part by the Office of Scientific Research and Development beginning in 1941B1942. This function was later assumed by the U.S. Atomic Energy Commission.

References

Hunter, F.T., A.F. Kip, and J.W. Irvine, Jr. ARadioactive Tracer Studies on Arsenic Injected as Potassium Arsenite. I. Excretion and Localization in Tissues.@The Journal of Pharmacology and Experimental Therapeutics. Vol. 76, No. 3, November 1942, pp. 207B220.  "

OT-45. Iodine Metabolism Studies in Graves=Disease Using Iodine-131

DURING THE EARLY 1940s, researchers at the Massachusetts Institute of Technology, Massachusetts General Hospital, and Boston City Hospital conducted studies on iodine uptake, retention, and excretion in hospital patients with Graves=disease using iodine-131 (I¹³¹). Twenty-two patients and two normal individuals participated as subjects.

Each subject was orally administered I¹³¹ as sodium iodide. Activity was measured in the thyroid gland by external counting and in subsequently collected urine samples. This procedure was followed by routine iodine therapy and, in 19 cases, surgical removal of the thyroid.

These studies showed that the largest percentages of iodine uptake occur at low dosage levels, and that administration of clinical doses of iodine will cause a decrease in uptake of radioiodine administered later. This work was supported by private funding and a grant from Harvard University. The MIT Radioactivity Center was supported in part by the Office of Scientific Research and Development beginning in 1941B1942. This function was later assumed by the U.S. Atomic Energy Commission.

References

Hertz, S., A. Roberts, and W.T. Salter. ARadioactive Iodine as an Indicator in Thyroid Physiology. IV. The Metabolism of Iodine in Graves=Disease.@Journal of Clinical Investigation. Vol. 21, No. 1, January 1942, pp. 25B29.  "

OT-46. Early Studies of Iron Metabolism in Red Blood Cells Using Iron-55 and Iron-59

THE FIRST TRACER STUDIES using both iron-55 (Fe⁵⁵) and iron-59 (Fe⁵⁹) as tracers for red blood cells were conducted at the Radioactivity Center of the Massachusetts Institute of Technology (MIT) in collaboration with the Medical Clinic of the Peter Bent Brigham Hospital and the Department of Medicine, Harvard Medical School, during the period 1941 to 1946. The purpose of these studies was to develop methods and demonstrate the usefulness of radioiron tracers for various physiological and clinical investigations on red blood-cell and iron metabolism in normal subjects, and hospital patients with various iron deficiency anemias.

These studies involved 48 human blood donors; 3 received intravenous injections of a mixture of Fe⁵⁵ and Fe⁵⁹ as ferric ammonium citrate: 6 received Fe⁵⁹, and 38 received Fe⁵⁵. Three of the latter also subsequently received injections of Fe⁵⁹. The calculated doses in these donors were estimated to have ranged from 0.05 to 0.2 roentgen per week. Residual Fe⁵⁵ activity in blood was measured for as long as 4 years in some of the subjects. Red blood cells from these donors were later transfused into 160 subjects in amounts ranging from 50 to 250 milliliters. These subjects were all normal, young adult males with active daily routines. In addition, Fe⁵⁵ or Fe⁵⁹ was administered to 65 patients in the wards of the Peter Bent Brigham Hospital for evaluation of various blood anemia conditions.

Results of these studies showed that double-tracer radioiron studies were useful for clinical investigations, and that both normal subjects and hospital patients tolerated the radioiron injections or labeled blood transfusions without detrimental radiation effects. This work was done under a contract, recommended by the Committee on Medical Research, by the Office of Scientific Research and Development with the Massachusetts Institute of Technology, in collaboration with the Peter Bent Brigham Hospital.

References

Peacock, W.C., R.D. Evans, J.W. Irvine, Jr., W.M. Good, A.F. Kip, S. Weiss, and J.G. Gibson, II. AThe Use of Two Radioactive Isotopes of Iron in Tracer Studies of Erythrocytes.@The Journal of Clinical Investigation. Vol. 25, No. 4, 1946, pp. 605B615.  "

OT-47. Studies on Absorption of Insulin Labeled with Iodine-131 in Subjects

THIS STUDY WAS CONDUCTED in approximately 1943 as a joint effort of the New England Deaconess Hospital in Boston, the Massachusetts Institute of Technology (MIT), Wallace & Tiernan Products, Inc. of Belleville, New Jersey, and the Nutrition Laboratory of the Carnegie Institution of Washington in Boston. The purpose of this study was to investigate the rate of absorption of insulin. The study subjects comprised 5 normal subjects and 10 diabetic patients.

Each subject was administered 25 units of insulin-4Biodoazobenzene labeled with iodine-131 (I¹³¹) by intravenous injection. The specific activity of the I¹³¹ and the total amount administered to each subject were not stated. The fraction of the administered activity in urine was measured 24 hours after injection. Blood-sugar levels were also determined in each subject.

Insulin absorption was found to occur at a similar rate in diabetics and normal subjects, although subjects with idiopathic (cause unknown) insulin resistance showed significant delay in insulin absorption due to prolonged residence of insulin in tissues. The MIT Radioactivity Center was supported in part by the Office of Scientific Research and Development beginning in 1941B1942. This function was later assumed by the U.S. Atomic Energy Commission.

References

Root, H.F., J.W. Irvine, Jr., R.D. Evans, L. Reiner, and T.M. Carpenter. AAbsorption of Insulin Labeled with Radioactive Iodine in Human Diabetes.@The Journal of the American Medical Association. Vol. 124, 1944, pp. 84B90.  "

OT-48. Studies of the Effects of Thiouracil on the Thyroid Gland Using Iodine-131

STUDIES WERE CONDUCTED in approximately 1943 at the Massachusetts General Hospital, Boston, and at the Radioactivity Center of the Massachusetts Institute of Technology (MIT) to evaluate the effects of thiouracil treatment on thyroid glands among a group of 19 patients with Graves=disease, all of whom were scheduled for surgical excision of their thyroids (thyroidectomy). Thiouracil had been used to treat hypertension, but it was also known to decrease the basal metabolic rate. Of the 19 patients (14 females, ages 20 to 53 years; 5 males, ages 18 to 61 years), 4 had histories of previous treatment with stable iodine.

Thyroid biopsies were obtained from five of the patients prior to the start of thiouracil treatment. All patients were treated with thiouracil alone in preparation for thyroidectomy. Thyroid uptake studies were conducted on 11 (9 females, 2 males) of the 19 patients. In these studies, iodine-131 (I¹³¹) was administered to 10 of the 11 patients 24 to 48 hours before thyroidectomy. The 11th patient received tracer iodine 5 days before beginning thiouracil treatment, and again on days 1, 7, and 12 of the treatment. All urine excreted by the patients was collected and analyzed for I¹³¹ content, and the percent of the administered activity remaining in the excised thyroid gland tissue was determined after surgical removal.

Results of this study showed that I¹³¹ excretion decreased in patients receiving thiouracil prior to thyroidectomy, and that subjects=basal metabolic rate decreased, indicating that thiouracil blocked the synthesis of thyroid hormone. This work was supported by grants from the Josiah Macy, Jr. Foundation and the John and Mary R. Markle Foundation. The MIT Radioactivity Center was supported in part by the Office of Scientific Research and Development beginning in 1941B1942. This function was later assumed by the U.S. Atomic Energy Commission.

References

Rawson, R.W., R.D. Evans, J.H. Means, W.C. Peacock, J. Lerman, and R.E. Cortell. AThe Action of Thiouracil upon the Thyroid Gland in Graves=Disease.@The Journal of Clinical Endocrinology,Vol. 4, No. 1, 1944, pp. 1B11.  "

OT-49. Studies on the Absorption of Ferrous and Ferric Iron Using Iron­59

A COLLABORATIVE STUDY involving researchers in the Department of Biochemistry and Medicine at Vanderbilt University Medical School in Tennessee, the University of Rochester School of Medicine in New York, the Louisiana State Medical School, and the Radioactivity Center of the Massachusetts Institute of Technology (MIT) was conducted between 1943 and 1944 to determine whether the ferrous or ferric salts of iron were better absorbed from the human gastrointestinal system. Nine patients (five white, four black) between the ages of 23 and 78 years, in various health conditions, were included in this study. The subjects included one male with an intestinal ulcer, one elderly woman with stomach cancer, and seven women with iron deficiency anemia or hemorrhagic iron deficiency.

Iron-59 (Fe⁵⁹) was administered with stable iron carrier as ferric ammonium citrate, ferric chloride, ferrous sulfate, or ferrous chloride. The amount of Fe⁵⁹ tracer added to the iron was not described. Two different forms of Fe⁵⁹-tagged iron were administered to each patient at different times to compare absorption efficiencies and rates of iron utilization. Measurements were made on blood samples from the subjects to determine absorption efficiency as percent uptake of ingested iron.

This research showed that the ferrous iron salt was much more readily absorbed and subsequently utilized than the corresponding ferric salt or ferric ammonium citrate fed under the same conditions. This study preceded a larger study on nutrition in pregnancy at Vanderbilt University. This research was supported by a grant from the Nutrition Foundation. The MIT Radioactivity Center was supported in part by the Office of Scientific Research and Development beginning in 1941B1942. This function was later assumed by the U.S. Atomic Energy Commission.

References

Hahn, P.F., E. Jones, R.C. Lowe, G.R. Meneely, and W. Peacock. AThe Relative Absorption and Utilization of Ferrous and Ferric Iron in Anemia as Determined with the Radioactive Isotope.@American Journal of Physiology. Vol. 143, No. 2, 1945, pp. 191B197.  "

OT-50. Studies to Determine Red Blood-Cell Volumes in Human Subjects Using Iron-55 and Iron-59

STUDIES WERE CONDUCTED during 1943 to 1946 at the Radioactivity Center of the Massachusetts Institute of Technology (MIT) in collaboration with the Medical Clinic of Peter Bent Brigham Hospital, the Surgical Research Department of Beth Israel Hospital, and the Department of Medicine, Harvard Medical School, of methods using iron-55 (Fe⁵⁵) and iron-59 (Fe⁵⁹) to determine the circulating red blood-cell volume in humans. Blood volume estimates were important in the study of various blood anemias, heart diseases, thyroid disorders, renal diseases, and pregnancy. Donor blood was mixed with Fe⁵⁵ and Fe⁵⁹ and transfused into a patient to determine red cell volume. The method was developed using one hospital patient with emphysema and polycythemia vera and two patients with anemia, and was further tested using 40 normal male subjects who received Fe⁵⁵- and Fe⁵⁹-labeled blood and blood dye. Earlier methods using colored dyes provided estimates of total plasma volume, and red cell volumes had previously been determined using carbon monoxide.

Dual isotope studies using Fe⁵⁵ and Fe⁵⁹ proved to be advantageous over earlier methods. The dual-isotope method was also adapted to study the post-transfusion survival of red blood cells. This work was done under a contract, recommended by the Committee on Medical Research, by the Office of Scientific Research and Development with the Massachusetts Institute of Technology, in collaboration with the Peter Bent Brigham Hospital.

References

Gibson, J.G. II, S. Weiss, R.D. Evans, W.C. Peacock, J.W. Irvine, Jr., W.M. Good, and A.F. Kipp. AThe Measurement of the Circulating Red Cell Volume by Means of Two Radioactive Isotopes of Iron.@The Journal of Clinical Investigation. Vol. 25, No. 4, 1946, pp. 616B626.

Gibson, J.G. II, W.C. Peacock, A.M. Seligman, and T. Sack. ACirculating Red Cell Volume Measured Simultaneously by the Radioactive Iron and Dye Methods.@The Journal of Clinical Investigation. Vol. 25, No. 6, 1946, pp. 838B847.  "

OT-51. A Study of Red Blood-Cell Survival in Stored and Transfused Blood Using Iron-55

BETWEEN 1943 AND 1947, a study was conducted at Evans Memorial Hospital, Boston University School of Medicine, Harvard Medical School, and the Radioactivity Center of the Massachusetts Institute of Technology (MIT) to evaluate the effectiveness of certain selected preservatives in maintaining the viability of red cells in blood stored for transfusion and post-transfusion. The value of blood transfusion had been well established during World War II, but the survival times of red blood cells in blood stored in blood banks had not been determined. There was concern that nonviable red blood cells could be harmful to the recipient.

An accepted diagnostic technique of using iron labeled with tracer iron-55 (Fe⁵⁵) to monitor metabolism was used in determining red blood-cell survival times in 16 different preservative solutions, and in recipients=blood post-transfusion. Transfusion recipients were normal healthy adult male or female medical students, interns, or hospital technicians who volunteered for the study and were matched for compatible blood type.

To determine red blood-cell survival times, Fe⁵⁵ as iron ammonium citrate was administered by intramuscular or intravenous injection to one of two selected healthy, young adult male donors. The second donor served as a source of blood for control studies. The first subject received two series of injections. In the first series, 4.68 milligrams of Fe⁵⁵ were administered in 20 injections over 71 days. In the second series, 8 months later, 4.36 milligrams of Fe⁵⁵ were administered by similar injections over 74 days. The amount of administered activity was not reported. Blood (400 to 500 milliliters) was then drawn from the donors into a preservative solution, and stored until use.

Transfusions of blood from the Fe⁵⁵-tagged donor were administered to 90 recipients; 88 recipients experienced no adverse effects of the transfusion, while 2 individuals developed mild fevers attributed to the dye solution used in the study. Each recipient received 100 milliliters of blood labeled with Fe⁵⁵. The specific activity of the donor=s and recipient=s whole blood, red cells, hemoglobin, and hemoglobin iron was determined by radioactivity measurements. The effectiveness of different techniques and preservation solutions to store whole blood was evaluated. The most effective preservative was an acid citrate-dextrose solution, and whole blood was found to have a satisfactory storage period of 21 days. This study was supported by the Office of Scientific Research and Development.

References

Ross, J.F., C.A. Finch, W.C. Peacock, and M.E. Sammons. ATheIn Vitro Preservation and Post-transfusion Survival of Stored Blood.@The Journal of Clinical Investigation. Vol. 26, 1947, pp. 687B703.  "

OT-52. Studies on Red Blood-Cell Survival During Storage and After Transfusion Using Iron-55 and Iron-59 Tracers

DURING 1943 TO 1947, collaborative studies were conducted by researchers at the Peter Bent Brigham Hospital, Massachusetts General Hospital, and the Radioactivity Center of the Massachusetts Institute of Technology on methods for blood preservation and the post-transfusion survival of preserved red blood cells.

Donor red blood cells were tagged with iron-55 (Fe⁵⁵) by administering the activity intravenously and allowing the Fe⁵⁵ to mix with donor blood. Pre-transfusion blood volumes in recipients were determined by transfusion of red cells tagged with iron-59 (Fe⁵⁹). The number of donors was not stated. All donors and most of the recipients were young male volunteers between 18 and 25 years of age with blood types from Groups O and A and free of disease or recent infections. Donors with Fe⁵⁵-labeled red blood cells were bled repeatedly, but not at less than 8-week intervals. Collected blood was cross-matched with recipient blood to ensure compatibility. Some of the recipients were hospital patients with various anemias, gastro-intestinal lesions, or cancer.

Each recipient received only one transfusion of labeled blood. Fifty-two subjects received transfusions of whole-blood tagged with Fe⁵⁹ tracer and 81 subjects received transfusions of packed or resuspended red blood cells tagged with a tracer dose of Fe⁵⁹. Samples of blood from donors and recipients were later analyzed for Fe⁵⁵ or Fe⁵⁹ activity. The percent of cells surviving in stored blood and in recipient blood was determined at different times after labeling.

Experiments were conducted to determine the best of 11 preservative solutions and 12 electrolyte solutions for storing whole blood for maximum red-cell survival time. Methods were developed for storing whole blood for up to 21 days. This study showed that most of the nonviable transfused red cells were cleared from recipient blood within 2 hours of transfusion, and iron from nonviable red cells was reutilized by the body. This study was supported by the Office of Scientific Research and Development.

References

Gibson, J.G. II, R.D. Evans, J.C. Aub, T. Sack, and W.C. Peacock. AThe Post-transfusion Survival of Preserved Human Erythrocytes Stored as Whole Blood or in Resuspension, After Removal of Plasma, by Means of Two Isotopes of Radioactive Iron.@Journal of Clinical Investigation. Vol. 26, 1947, pp. 715B738.

Gibson, J.G. II, W.C. Peacock, R.D. Evans, T. Sack, and J.C. Aub. AThe Rate of Post-transfusion Loss of Non-viable Stored Human Erythrocytes and the Re-utilization of Hemoglobin-derived Radioactive Iron.@Journal of Clinical Investigation. Vol. 26, 1947, pp. 739B746.  "

OT-53. Effect of Phytate on the Absorption of Iron-59 and Iron-55

A STUDY WAS CONDUCTED in 1946 by the Departments of Food Technology and Physics of the Massachusetts Institute of Technology (MIT) and by the Fernald State School in Waverly, Massachusetts.

Fifteen boys, ages 12 to 17 years, living at the Fernald School, with I.Q.s ranging between 65 and 70, were fed breakfasts containing either iron-59 (Fe⁵⁹) or iron-55 (Fe⁵⁵) in the milk or water. The amount of radioiron received by each subject differed according to body weight. No food was eaten before or until 5 hours after the test meals, each of which contained differing amounts of phytates, a natural ingredient in rolled oats.

The experiment was done because there was concern that certain diets rich in cereal might affect iron absorption and thus result in malnutrition, especially in developing countries where iron-rich foods are not plentiful. These concerns were based upon earlier studies which showed that bread, which also contains phytates, could inhibit the uptake of dietary iron.

The general conclusion of this study was that iron supplements to the diet should not be given with meals. In addition, children living in institutions could continue to eat oatmeal without concern for negative effects, so far as iron uptake was concerned. In 1994, the Massachusetts Task Force investigation estimated that the absorbed dose to each of the participants in the study was approximately 300 millirems. The 1946 research was supported by a grant from the Quaker Oats Company. The MIT Radioactivity Center was supported in part by the Office of Scientific Research and Development beginning in 1941B1942. This function was later assumed by the U.S. Atomic Energy Commission.

References

Sharpe, L.M., W.C. Peacock, R. Cooke, and R.S. Harris. AThe Effect of Phytate and Other Food Factors on Iron Absorption.@The Journal of Nutrition. Vol. 41, No. 3, 1950, pp. 433B446.

Sharpe, L.M., R.S. Harris, W.C. Peacock, and R.C. Cooke. AThe Effect of Phytate and Other Food Ingredients on the Absorption of Radioactive Iron.@In Federation Proceedings. Vol. 7, No. 1. March 1948.

The Task Force on Human Subject Research. AA Report on the Use of Radioactive Materials in Human Subject Research that Involved Residents of State-Operated Facilitates within the Commonwealth of Massachusetts from 1943 through 1973.@April 1994.  "

OT-54. Measurements of Radon-222 Absorption Through Skin

A JOINT STUDY WAS CONDUCTED in approximately 1946 by the New York Medical College (Metropolitan Hospital) and the Radioactivity Center of the Massachusetts Institute of Technology (MIT) to determine the scientific basis, if any, for contemporary claims of therapeutic effects on deep structures from topical application of ointment containing radon-222 (Rn²²²).

The amounts of Rn²²² in expired air were used as a measure of absorption of Rn²²² into the bloodstream from the ointment applied to the body surface. The ointment, containing 49 micrograms of Rn²²² per gram of lanolin, was applied in thicknesses varying between 2 and 3 millimeters to: a large varicose ulcer on the leg of one subject; intact skin on the legs of two subjects with other chronic diseases; and one normal subject. The applications were covered immediately with oil silk or glass and then sealed with layered adhesive.

In the first experiment, samples of exhaled air were taken after 20, 160, and 270 minutes and analyzed for Rn²²² content. This study showed that 2.4 percent of radon applied to the leg ulcer, and about 0.08 to 0.13 percent of radon in the ointment applied to intact skin were exhaled after 270 minutes.

In a second experiment, the subject with the leg ulcer and the normal subject were monitored at intervals over a period of 23 hours following the application. They exhaled 10 and 4.5 percent, respectively, of the total Rn²²² in the ointment application. This study demonstrated that Rn²²² was absorbed into the blood from topically applied ointment and that absorption was greater through nonintact skin than through intact skin. The results indicated a potential for radiation effects to be induced in structures deeper than would have been predicted had Rn²²² remained at the application site. The study did not, however, resolve the question of whether the amount of Rn²²² made available to these structures by absorption and transportation was sufficient to induce effects of therapeutic value. The MIT Radioactivity Center was supported in part by the Office of Scientific Research and Development beginning in 1941B1942. This function was later assumed by the U.S. Atomic Energy Commission.

References

Lange, K., and R.D. Evans. AAbsorption of Radon through the Skin and Its Exhalation through the Lungs.@Radiology. Vol. 48, No. 5, 1947, pp. 514B516.  "

OT-55. Studies of the Urinary Excretion of Iodine Using Iodine-131

RESEARCHERS IN THE THYROID CLINIC of the Massachusetts General Hospital and the Radioactivity Center of the Massachusetts Institute of Technology (MIT) collaborated on a study in approximately 1946 to 1948 of the rates of iodine excretion rates by subjects with normal thyroids and by hospital patients with thyroid disorders.

Three groups of subjects were involved, including 25 hospital patients with untreated thyrotoxicosis, 6 patients with myxedema, and 15 normal-thyroid patients who were hospitalized for illnesses not related to thyroid function.

Each subject was given 100 of microcuries iodine-131 (I¹³¹) with 100 micrograms stable sodium iodide carrier orally, usually in the morning before breakfast. Urine samples were then collected from each subject either as 6-hour, 12­hour, or 24-hour specimens up to 48 hours after iodine ingestion. The amount of I¹³¹ in each urine specimen was determined and results for each group were compared.

The results of this study showed that the urinary excretion of iodine in the group of thyrotoxic patients was considerably less than in the group with normal thyroid function. However, patients with myxedema generally excreted more iodine than subjects with normal thyroid function. The sponsor of this research was not stated, although the author was a Rockefeller fellow during the study period. Funding for the MIT Radioactivity Center was provided by the U.S. Atomic Energy Commission.

Reference

Skanse, B. ARadioactive Iodine: Its Use in Studying the Urinary Excretion of Iodine by Humans in Various States of Thyroid Function.@Acta Medica Scandinavica. Vol. 131, No. 3, 1948, pp. 251B268.  "

OT-56. Study of the Uptake of Iodine in Fetal Thyroids Using Iodine-131

A COLLABORATIVE STUDY was conducted in approximately 1947 by researchers at the Massachusetts General Hospital, the Boston Lying-In Hospital, and the Radioactivity Center of the Massachusetts Institute of Technology (MIT) to determine the age at which the human fetal thyroid begins to function and accumulate iodine.

Nine pregnant women with organic disease and scheduled for therapeutic abortions were injected with tracer amounts of iodine-131, 24 to 48 hours before an operation to remove the fetus. The intact fetus was obtained and measured for approximate age, fixed in formalin, and sectioned for histological analysis. The amount of administered activity was not reported. The radioactivity in the fetal thyroids was determined by direct counting.

Iodine-131 was not found in thyroids of fetuses ranging in age from 7 to 12 weeks, but amounts increasing with age were found in fetuses ranging in age from 14 to 32 weeks.

These studies showed that radioiodine could be therapeutically administered until the 4th month of pregnancy without concern for fetal uptake. Funding for the MIT Radioactivity Center was provided by the U.S. Atomic Energy Commission.

References

Chapman, E.M., G.W. Corner, D. Robinson, and R.D. Evans. AThe Collection of Radioactive Iodine by the Human Fetal Thyroid.@The Journal of Clinical Endocrinology. Vol. 8, No. 9, 1948, pp. 717B720.  "

OT-57. Red Blood-Cell Volumes and Hematocrit in Normal Pregnancy Using Iron-55

A COLLABORATIVE STUDY was conducted in approximately 1948 by researchers in the Department of Obstetrics and Gynecology at the Harvard Medical School, the Boston Lying-In Hospital, and the Radioactivity Center of the Massachusetts Institute of Technology (MIT) to determine the circulating red blood-cell mass in women during pregnancy and after childbirth. The subjects were 12 normal patients at the Boston Lying-In Hospital who were pregnant and near full-term.

Six to 12 separate studies were made on each patient to determine red cell volume, plasma volume, and extracellular space. Red cell volumes were determined by tagging blood donated by healthy male donors with iron-55 (Fe⁵⁵), administering the tagged blood to the female subjects, and obtaining 15 milliliters of blood from the subjects at various times during and after pregnancy. Blood samples were then counted for Fe⁵⁵ content. The amount of Fe⁵⁵ administered to each woman as Fe⁵⁵-labeled blood ranged from 2 to 12 microcuries.

This study showed that red blood-cell volume increased by 40 percent during normal pregnancy and continued to increase for 1 week after childbirth. Red blood-cell volumes returned to normal 60 days after delivery. Blood hematocrit decreased 8 to 15 percent during pregnancy. This study was supported by the Charles H. Hood Foundation, the Office of Naval Research, the National Institutes of Health, and the U.S. Atomic Energy Commission.

References

Caton, W.L., C.C. Roby, D.E. Reid, and J.G. Gibson II. APlasma Volume and Extravascular Fluid Volume During Pregnancy and the Puerperium.@American Journal of Obstetrics and Gynecology. Vol. 57, 1949, p. 471B481.

Caton, W.L., C.C. Roby, D.E. Reid, R. Caswell, C.J. Maletskos, R.G. Fluharty, and J.G. Gibson II. AThe Circulating Red Cell Volume and Body Hematocrit in Normal Pregnancy and the Puerperium.@American Journal of Obstetrics and Gynecology. Vol. 61, No. 6, 1951, pp. 1,207B1,217.  "

OT-58. Studies of Iron Storage and Utilization Using Iron-55 and Iron-59

STUDIES WERE CONDUCTED jointly by investigators at the Harvard Medical School and the Radioactivity Center of the Massachusetts Institute of Technology (MIT), in collaboration with Peter Bent Brigham Hospital during 1948 to 1949 on the dynamic relationship between stored iron and circulating iron in normal subjects and in patients with a variety of hematologic disorders.

The total number of subjects in these studies was 61; these included 9 normal male volunteers between the ages of 24 and 30 years, 6 patients with acute or chronic blood loss representing various degrees of iron-deficiency anemia, 3 subjects with other diseases not related to iron metabolism, and 49 subjects with either hemochromatosis; refractory anemia; uremia and other anemias; infection; malaria; cancer liver disease; endocrinological disease; and polycythemia vera.

Iron-55 (Fe⁵⁵) and iron-59 (Fe⁵⁹) from the MIT cyclotron were prepared as ferric chloride, ferric ammonium citrate, or ferrous ammonium sulfate with stable iron carrier. About 0.5 microcurie of Fe⁵⁵ or Fe⁵⁹ was administered to the subjects by intravenous injection. The radioactive iron then entered the hemoglobin cycle and red blood cells labeled with Fe⁵⁵ or Fe⁵⁹ began to appear in the circulation, reaching a plateau in 2 to 3 weeks. Samples of venous blood were drawn from the subjects at various time points after injection and counted for Fe⁵⁵ or Fe⁵⁹ activity to determine the utilization of radioiron over time, the labeled red cell population, and other blood-cell parameters.

This study showed that changes in iron utilization were due to alterations in body storage of iron and were affected by various disease conditions. This work was supported by a grant from the U.S. Public Health Service. Funding for the MIT Radioactivity Center was provided by the U.S. Atomic Energy Commission.

References

Finch, C.A., J.G. Gibson, W.C. Peacock, and R.G. Fluharty. AIron MetabolismCUtilization of Intravenous Radioactive Iron.@Blood: The Journal of Hematology. Vol. 4, No. 8, 1949, pp. 905B927.  "

OT-59. Study of Iron Turnover by Red Blood Cells Using Iron-55 and Iron-59

A STUDY WAS CONDUCTED at the Harvard Medical School and the Radioactivity Center of the Massachusetts Institute of Technology (MIT) during 1948 to 1949 on the disappearance of iron from red blood cells in circulation. Blood from donors was labeled with either iron-55 (Fe⁵⁵) or iron-59 (Fe⁵⁹) from the MIT cyclotron and was readministered to subjects. Blood from these subjects was later drawn, characterized, and readministered to other subjects to determine the lifetimes of the labeled red blood cells.

Recipients of the tagged donor blood included hospital patients with various blood disorders. These patients included one 6-year-old girl with aplastic anemia, a 4-year-old boy and a 4-year-old girl with Cooley=s anemia, and a patient with hemochromatosis. These were subjects who required frequent blood transfusions.

In another series of observations, three normal male subjects were given Fe⁵⁵ intravenously and 200 to 400 milligrams of stable iron as ferrous sulfate by mouth after meals. Blood was then drawn from the subjects and counted for Fe⁵⁵ or Fe⁵⁹ activity to determine the life span of red blood cells and the reutilization of iron.

This study showed that the reutilization of radioiron from broken-down red cells is blocked by the presence of enlarged iron stores and by bone marrow dysfunction in subjects. The life span of red blood cells was also determined. The iron turnover was found to be about 1 percent per day in man. This work was supported by a grant from the National Institutes of Health, the Office of Naval Research, the Charles P. Hood Foundation, and the U.S. Atomic Energy Commission.

References

Finch, C.A., J.A. Wolff, C.E. Rath, and R.G. Fluharty. AIron Metabolism: Erythrocyte Iron Turnover.@The Journal of Laboratory and Clinical Medicine. Vol. 34, No. 11, 1949, pp. 1,480B1,490.  "

OT-60. Studies of the Metabolism of Maternal Iron in Newborn Infants Using Iron-55

A COLLABORATIVE STUDY was conducted during 1948 to 1950, by researchers in the Department of Pediatrics of Harvard Medical School, the Boston Lying-In Hospital, Children=s Hospital, Peter Bent Brigham Hospital, Boston and the Radioactivity Center of the Massachusetts Institute of Technology. The purpose of this study was to determine the persistence and utilization of iron from maternal blood in newborn infants.

The study involved 11 females who had participated while pregnant in a previous blood study using iron-55 (Fe⁵⁵) (Caton et al., 1949, 1951), and the 16 infants born to them. The total activity of Fe⁵⁵ administered as tagged red blood cells to each pregnant woman ranged from about 2 to 12 microcuries. The estimated doses to their infants were estimated to be 30 to 354 millirads.

Seven to 15 milliliters of maternal blood were obtained at time of delivery, and similar amounts of the infants=blood were obtained at delivery and at varying ages thereafter for up to 32 months. Each blood sample was analyzed for Fe⁵⁵ cell count, total iron, and hemoglobin.

This study showed that all infant hemoglobin iron was maternal in origin and that dietary iron did not contribute to infant hemoglobin until 3 to 4 months after birth. At 1 year, maternal iron constituted 70 percent of total hemoglobin iron. This study was supported by the American Cancer Society, the Office of Naval Research, the National Institutes of Health, and the U.S. Atomic Energy Commission.

References

Caton, W.L., C.C. Roby, D.E. Reid, and J.G. Gibson II. APlasma Volume and Extravascular Fluid Volume During Pregnancy and the Puerperium.@American Journal of Obstetrics and Gynecology. Vol. 57, 1949, p. 471B481.

Caton, W.L., C.C. Roby, D.E. Reid, R. Caswell, C.J. Maletskos, R.G. Fluharty, and J.G. Gibson II. AThe Circulating Red Cell Volume and Body Hematocrit in Normal Pregnancy and the Puerperium.@American Journal of Obstetrics and Gynecology.Vol. 61, No. 6, 1951, pp. 1,207B1,217.

Smith, C.A., R.B. Cherry, C.J. Maletskos, J.G. Gibson II, C.C. Roby, W.L. Caton, and D.E. Reid. APersistence and Utilization of Maternal Iron for Blood Formation During Infancy.@The Journal of Clinical Investigation. Vol. 34, No. 9, 1955, pp. 1,391B1,402.  "

OT-61. Thyroid Function Studies Using Iodine-131

DURING THE EARLY 1950s, researchers at the Fernald State School, Waverly, Massachusetts; the Harvard Medical School; the Tufts Medical School; and the Massachusetts Institute of Technology conducted studies on thyroid function in patients diagnosed with myotonia dystrophia (a genetic neuro-endocrine disorder associated with muscular dystrophy) using iodine-131 (I¹³¹).

Six male patients were orally administered 54 microcuries of I¹³¹. Activity was measured by external counting in urine samples during the next 24 hours, and in the thyroid over the next 8 days.

The results of these studies showed that although the thyroid gland was operating at a lower than normal capacity in the patients, iodine uptake by their thyroids, iodine excretion rates, and protein-bound iodine values appeared to be normal. This work was supported by the U.S. Atomic Energy Commission.

References

Benda, C.E., C.J. Maletskos, J.C. Hutchinson, and E.B. Thomas. AStudies of Thyroid Function in Myotonia Dystrophica.@American Journal of the Medical Sciences. Vol. 228, No. 6, December 1954, pp. 668B672.  "

OT-62. Interlaboratory Comparison of the Reliability of the Measurement of Cesium-137 in Humans

AN INTERCOMPARISON STUDY was conducted by the U.S. Atomic Energy Commission (AEC) during the period 1962 to 1966 to evaluate and compare the reliability of direct in vivo counting techniques for measurement of cesium-137 (Cs¹³⁷) in humans at AEC-affiliated research facilities. The purpose was to improve and assure comparability between the facilities=Cs¹³⁷ measurements.

This intercomparison study was coordinated by an ad hoc committee appointed by the AEC Division of Biology and Medicine, with two of the committee members serving as volunteer subjects. Each was of medium body build. One subject was administered 0.2 to 0.3 microcurie of Cs¹³⁷ by intravenous injection. The second subject was not given Cs¹³⁷ or any other radionuclide; he served as the Anormal@subject, representing an average member of the general population whose only exposure to Cs¹³⁷ was from weapons-testing fallout directly or through the environment. The levels of radioactivity from Cs¹³⁷ and potassium-40 (K⁴⁰, a natural component of human tissue) in the two subjects were measured using whole-body counters at 16 AEC or private laboratories nationwide. The results at individual laboratories were evaluated against national standards and compared across the laboratories.

Physiological rather than physical variables appeared to account for observed interlaboratory measurement differences. Study results indicated that the laboratories were capable of reliable measurements of Cs¹³⁷ and K⁴⁰ in humans and therefore were capable of accurately measuring changes in the levels of Cs¹³⁷ to which their area populations were exposed as the result of nuclear weapons testing. This work was supported by the U.S. Atomic Energy Commission.

References

Maletskos, C.J., P.N. Dean, S.A. Lough, and C.E. Miller. AIntercomparison of the Reliability of Body Cesium-137 Measurements on Human Beings.@Health Physics. Vol. 13, 1967, pp. 1,307B1,319.

Maletskos, C.J., P.N. Dean, S.A. Lough, and C.E. Miller. AIntercomparison of the Reliability of Body Cesium-137 Measurements on Human Beings.@Washington, D.C.: U.S. Atomic Energy Commission, Division of Biology and Medicine, TID-23740, June 8, 1967.  "

OT-63. Metabolic and Gastrointestinal Absorption Studies with Short-Lived Decay Products of Radium and Thorium

BETWEEN 1961 AND 1965, researchers at the Massachusetts Institute of Technology (MIT) conducted studies on the metabolism and gastrointestinal absorption of thorium and radium in normal human beings. The purpose of the studies was to determine the health impact of thorium-228 (Th²²⁸), which was present in radium paint used and ingested by dial painters during the 1920s.

Seven females and 13 males ranging in age from 63 to 83 years, participated as subjects. During the study, subjects were housed at either the MIT Infirmary or the Sancta Maria Hospital adjacent to MIT. Six of the subjects received intravenous injections of radium-224 (Ra²²⁴), while another six received intravenous injections of thorium-234 (Th²³⁴). One received Ra²²⁴ orally, another received Th²³⁴ orally, and the remaining six received an oral mixture of Ra²²⁴ and Th²³⁴. The purpose of injecting known amounts of Ra²²⁴ and Th²³⁴ was to calibrate the various measurements. Advantage was taken of the calibration period to provide information on the short-term metabolism of radium and thorium, nearly unknown at the time.

The administration of Ra²²⁴ for the calibration and absorption measurements ranged from 0.24 to 3.13 microcuries; that of Th²³⁴, from 1.2 to 247 microcuries. The oral administration of these isotopes was in the form of simulated radium paint. Activity levels were subsequently measured in blood, urine, and feces samples. Further levels were measured in the breath and in various parts and the entire body.

The results showed that there was little Th²²⁸ absorption and therefore, the internal radiation dose from the initial Th²²⁸ was less than 5 percent of that of its parent Ra²²⁸, and considerably less than the combined internal dose from Ra²²⁶ and Ra²²⁸. Consequently, the dose from Th²²⁸ could be ignored and the MIT subject group could remain intact for further dose-response and epidemiological studies. This work was supported by the U.S. Atomic Energy Commission. (This experiment was referenced in the Markey report.)

References

Maletskos, C.J., H.P. Anderson, A.G. Braun, H.F. Braun, J.F. Byrum, S.D. Clark, M.M. Costello, E.D. Dillon, J.A. Foley, J.E. Gary, A.T. Keane, J.A. Kelly, M. Lubin, M.M. Shanahan, and N.C. Telles. ADifferential Uptake of Elements 88 and 90 Following Oral Ingestion in Human Beings.@Radium and Mesothorium Poisoning and Dosimetry and Instrumentation Techniques in Applied Radioactivity. Cambridge, MA: Massachusetts Institute of Technology (MIT). MIT Annual Progress Report, MIT-952-2, 1965, pp. 69B79.

Maletskos, C.J., A.T. Keane, N.C. Telles, and R.D. Evans. AThe Metabolism of Intravenously Administered Radium and Thorium in Human Beings and the Relative Absorption from the Human Gastrointestinal Tract of Radium and Thorium in Simulated Radium Dial Paints.@Radium and Mesothorium Poisoning and Dosimetry and Instrumentation Techniques in Applied Radioactivity. Cambridge, MA: Massachusetts Institute of Technology (MIT). MIT Annual Progress Report, MIT-952-3, 1966, pp. 202B317.

Maletskos, C.J., A.T. Keane, N.C. Telles, and R.D. Evans. ARetention and Absorption of Ra²²⁴ and Th²³⁴ and Some Dosimetric Considerations of Ra²²⁴ in Human Beings.@In Delayed Effects of Bone-Seeking Radionuclides, edited by C.W. Mays, pp. 29B49. Salt Lake City: University of Utah Press, 1969.  "

OT-64. Comparison of Iodine-123 and Iodine-131 for Thyroid Uptake Studies

IN 1973, A STUDY was conducted at the Mayo Clinic, Rochester, Minnesota, to compare the suitability of iodine-123 (I¹²³) for measuring iodine uptake by the thyroid with that of iodine-131 (I¹³¹). Forty-two patients were studied. The patients displayed a wide range of thyroid disorders, but were generally free from gastrointestinal and kidney disorders, and had been referred for an iodine uptake test.

Thirty-two patients ingested a gelatin capsule containing 100 microcuries of I¹²³ and a capsule containing 2 to 5 microcuries of I¹³¹. Six subjects ingested 5 microcuries of I¹³¹ in aqueous solution. Four other patients ingested a gelatin capsule containing 10 to 13 microcuries of I¹³¹. The iodine activity in each subject was determined after 6 and 24 hours. In a few patients, uptakes were also measured at one or more additional times, such as 0.5, 1, 2, or 4 hours. Counts were obtained over the thighs of subjects to provide background information. The gel filler in one commercially available type of capsule inhibited absorption and uptake of the I¹³¹; otherwise, the I¹²³ and I¹³¹ were taken up by the thyroid at identical rates. This research was supported by the U.S. Atomic Energy Commission.

References

Robertson, J.S., M. Verhasselt, and H.W. Wahner. AThe Use of Iodine-123 for Thyroid Uptake Measurement and Depress of the I¹³¹ Thyroid Uptake by Incomplete Dissolution of Capsule Filler.@Journal of Nuclear Medicine. Vol. 15, No. 9, 1974, pp. 770B774.  "

OT-65. Iodine-131 Localization

FROM APPROXIMATELY 1947 TO 1951, extensive clinical and postmortem studies were conducted on nine patients at the Memorial Center for Cancer and Allied Disease in New York to learn more about the localization and effects of iodine-131 (I¹³¹). The subjects of this study were six women and three men between 37 and 80 years of age and near death with various diseases. Seven subjects had thyroid cancer with metastases. Of these, five had histories of prior therapeutic administrations of I¹³¹. One subject had undergone a partial thyroidectomy for hyperthyroidism 30 years earlier. Another subject had a goiter.

In all cases, carrier-free I¹³¹ was administered in amounts varying from 1.9 to 250 millicuries in anticipation of postmortem studies. Two of the subjects received the I¹³¹ by injection; the remainder of the administrations were oral. The interval between the administration of the I¹³¹ for the purpose of postmortem studies and death, ranged from 8 hours to 35 days. Tissue samples were taken at autopsy and analyzed.

Study findings confirmed earlier reports that I¹³¹ localizes in the thyroid and in thyroid cancer metastases to levels that vary with histologic type. No significant localization was observed in other organs or tissues examined. The study showed that I¹³¹ localized exclusively in the thyroid and that no effects directly attributable to I¹³¹ were induced in other tissues. Because of the shot duration of the study, no conclusions were made on the potential long-term effect of I¹³¹. This work was supported jointly by the Office of Naval Research and the U.S. Atomic Energy Commission.

References

Godwin, J.T., B.J. Duffy, P.J. Fitzgerald, J.B. Trunnel, and R.W. Rawson. AThe Pathological Effects and Radioauthographic Localization of I¹³¹ in Humans.@Cancer. Vol. 4, Sept. 1951, pp. 936B951.  "

OT-66. Tolerance to Whole-Body Irradiation of Patients with Advanced Cancer

FROM 1942 TO 1944, researchers at Memorial Hospital in New York City (now known as the Memorial Sloan-Kettering Cancer Center), conducted studies to determine the clinical and hematological effects of prolonged daily exposure to whole-body high-voltage x-ray irradiation. Seven male and one female advanced cancer patients, ranging in age from 25 to 64 years, were selected as subjects. Each was exposed to filtered 180-kilovolt x-rays with exposure rates from 0.85 to 1.65 roentgens per hour for daily exposures of 10 to 15 roentgens. Six subjects received total exposures of 300 roentgens over 20 or 30 days. Treatment was discontinued for the other two subjects at 150 and 161 roentgens due to their deteriorating health. Three of the six subjects who received the total projected dose were followed for 7 to 19 months after exposure. The other three were followed for only 1 to 4 months because of declining health and death.

The results of these studies did not show any alterations in blood count or any stimulation of tumor growth that could be ascribed to radiation exposure, indicating that a whole-body exposure of 300 roentgens could be well-tolerated by healthy individuals. This work was supported by the Manhattan Engineer District.

References

Craver, L.F. ATolerance to Whole-Body Irradiation of Patients with Advanced Cancer.@Industrial Medicine on the Plutonium Project. Edited by Robert S. Stone, New York: McGraw-Hill, 1951, pp. 485-498.

Craver, L.F. ATolerance to Whole-Body Irradiation of Patients with Advanced Cancer.@MMES/X-10/Vault, Central Files, CH-3369.  "

OT-67. Modification of the Distribution and Excretion of Lanthanum-140 by Chelating Agents

IN 1952, SCIENTISTS at Montefiore Hospital in New York conducted a study to investigate why so little lanthanum as the lanthanum-140 (La¹⁴⁰)Bcomplex with ethylenediaminetetraacetic acid (EDTA) was directly excreted in urine through the kidneys, compared to the urinary excretion of other metal-EDTA complexes. An unreported number of hospital patients participated as subjects of this study.

Each subject was administered 200 microcuries of La¹⁴⁰ complexed with the chelating agent EDTA. The subject was catheterized to facilitate urine collection for La¹⁴⁰ analysis. Urine and blood were collected at frequent intervals to determine the clearance and excretion of La¹⁴⁰-EDTA from the body. Calcium-EDTA was then administered to determine its 7enhancing effect on La¹⁴⁰ clearance. Lanthanum-140Bchloride was then administered (to the same or another subject) for comparison, and was then followed with calcium-EDTA.

This work showed that lanthanum was only slightly cleared (10 to 15 percent) using EDTA, due to exchange for calcium. The fact that the effectiveness of lanthanum-removal by the chelating agent EDTA decreases with time suggested its use as an investigative tool. This study was supported by the U.S. Atomic Energy Commission.

References

Hart, H., and Laszlo, D. AModification of the Distribution and Excretion of Radioisotopes by Chelating Agents.@Science. Vol. 118, 1953, pp. 24B25.  "

OT-68. Metabolism Studies Using Strontium-85 and Calcium-45

DURING THE MID-1950s, researchers at Columbia University and Montefiore Hospital in New York City conducted metabolism studies using strontium-85 (Sr⁸⁵) and calcium-45 (Ca⁴⁵). The purpose of these studies was to obtain data that might be relevant to the metabolism of strontium-90, a product of nuclear fission.

Twelve hospital patients ranging in age from 49 to 72 years, including 10 terminally ill cancer patients, participated as subjects. The cancer patients received simultaneous intravenous injections of 1.5 microcuries of Sr⁸⁵ and 0.4 microcurie of Ca⁴⁵ per kilogram of body weight. The other two patients received only one injection of either Sr⁸⁵ or Ca⁴⁵.

These studies showed that the isotopes were evenly divided between bone and soft tissue shortly after administration, but after 4 months, 99 percent of the Sr⁸⁵ and Ca⁴⁵ remaining in the body resided in bone. This work was supported by the U.S. Atomic Energy Commission. (This experiment was referenced in the Markey report.)

References

Schulert, A.R., E.A. Peets, D. Laszlo, H. Spencer, M. Charles, and J. Samachson. AComparative Metabolism of Strontium and Calcium in Man.@International Journal of Applied Radiation and Isotopes. Vol. 4, 1959, pp. 144B153.  "

OT-69. Strontium Metabolism Studies Using Strontium-85

DURING THE MID-1950s, researchers at Montefiore Hospital in New York City conducted studies on the human uptake, distribution, and excretion of strontium using strontium-85 (Sr⁸⁵). These studies arose from concerns about human hazards from strontium-90, a nuclear fission product.

Four hospital patients participated as subjects. Each subject received two intravenous injections of 0.1 to 0.4 microcurie of Sr⁸⁵ per kilogram of body weight: one injection with stable calcium, and one without. Urine, feces, and plasma samples were analyzed over the next 48 hours for Sr⁸⁵. One subject underwent a second series of tests in which the injections were administered over a 5-hour period.

The results of these studies showed that strontium levels in plasma declined rapidly, that the kidneys are the main excretion route, that rate of excretion depends upon bone metabolism rate, and that simultaneous administration of calcium enhances strontium excretion. This work was supported by the U.S. Atomic Energy Commission.

References

Spencer, H., M. Brothers, E. Berger, H.E. Hart, and D. Laszlo. AStrontium-85 Metabolism in Man and Effect of Calcium on Strontium Excretion.@In Proceedings of the Society for Experimental Biology and Medicine. Vol. 91, JanuaryBApril 1956, pp. 155B157.  "

OT-70. Studies on EDTA and Strontium Excretion Using Strontium-85

DURING THE MID-1950s, researchers at Montefiore Hospital in New York City conducted studies on the effect of ethylenediaminetetraacetic acid (EDTA) on the excretion of strontium in humans using strontium-85 (Sr⁸⁵). One female and two male cancer patients ranging in age from 40 to 70 years participated as subjects.

Each subject received two intravenous injections of 0.1 to 0.4 microcurie of Sr⁸⁵ per kilogram of body weight, accompanied by several intravenous injections of EDTA over several days. Strontium-85 activity was measured in plasma, urine, and fecal samples collected over the course of the study.

The results of these studies showed an inhibition of urinary excretion of Sr⁸⁵ when EDTA was administered, followed by an excess excretion when the EDTA was discontinued. This work was supported by the U.S. Atomic Energy Commission.

References

Spencer, H., J. Samachson, and D. Laszlo. AEffect of Ethylenediaminetetraacetic Acid on Radiostrontium Excretion in Man.@In Proceedings of the Society for Experimental Biology and Medicine. Vol. 97, JanuaryBApril 1958, pp. 565B567.  "

OT-71. Comparative Metabolism Studies Using Strontium-85 and Calcium­45

DURING THE MID-1950s, researchers at Montefiore Hospital in New York City conducted studies on the metabolism of strontium and calcium using strontium-85 (Sr⁸⁵) and calcium-45 (Ca⁴⁵). Six patients ranging in age from 54 to 72 years participated as subjects.

Each subject was orally administered 0.1 to 0.4 microcurie of Sr⁸⁵ per kilogram of body weight. Activity was counted in blood, urine, and stool samples for 12 to 40 days. Two of these subjects received an oral administration of Ca⁴⁵ prior to the Sr⁸⁵ and activity was measured in a similar manner. At the completion of the oral administration studies, four of the subjects were intravenously administered another 0.1 to 0.4 microcurie of Sr⁸⁵ per kilogram of body weight and activity was measured in plasma, urine, and stool samples for 14 to 16 days.

These studies showed that strontium was poorly absorbed in the gastrointestinal tract, that the main route of strontium excretion was through the kidneys to urine regardless of the means of administration, and that significantly less strontium than calcium was retained in the body. This work was supported by the U.S. Atomic Energy Commission.

References

Spencer, H., D. Laszlo, and M. Brothers. AStrontium-85 and Calcium-45 Metabolism in Man.@The Journal of Clinical Investigation. Vol. 36, JanuaryBJune 1957, pp. 680B688.  "

OT-72. Efforts to Increase the Rate of Strontium-85 Excretion

A STUDY WAS CONDUCTED in 1957 at the Montefiore Hospital in New York City to determine whether the natural excretion of radiostrontium by man could be accelerated by administering calcium and ammonium chloride. This study was conducted using three hospital patients: a 67-year-old female with breast cancer, a 74-year-old male with previous cancer of the larynx but no evidence of remaining disease and otherwise healthy, and a 58-year-old male with severe osteoarthritis of both hips.

Four separate tests with radiostrontium were conducted on each of the patients while they were maintained on a low-calcium diet. Strontium-85 (Sr⁸⁵) as strontium chloride was administered intravenously to each of the patients at the start of each of the four experiments. The amounts of Sr⁸⁵ administered ranged from 0.1 to 0.4 microcurie per kilogram body weight of the patient for each injection. After injection, the patients were given calcium gluconate, ammonium chloride, or both to determine whether these agents had any effect on the skeletal retention of strontium.

The results of this study showed that urinary calcium and radiostrontium excretion increased markedly when calcium gluconate was administered intravenously or ammonium chloride was given orally to the patients. This study was supported by the National Cancer Institute and the U.S. Atomic Energy Commission.

References

Spencer, H., J. Samachson, B. Kabakow, and D. Laszlo. AFactors Modifying Radiostrontium Excretion in Man.@Clinical Science. Vol. 17, 1958, pp. 291B301.  "

OT-73. Decontamination of Skin Contaminated with Carbon-14, Fission Products, Tantalum-182, and Alpha Emitters

DURING THE EARLY 1950s, researchers at Foster D. Snell, Inc., conducted studies for the U.S. Army on the effectiveness of various detergents and chemical agents to remove radioactive contamination from human skin surfaces and hair. The subjects for these studies ranged in age from 18 to 66 years.

The arms and hands of study participants were exposed to various media containing carbon-14, unspecified mixed-aged fission products in soil or synthetic soil, neutron-activated soil, samples of soil from the Nevada Test Site containing fallout, or liquid solutions of mixed-aged fission products or alpha-emitting radionuclides.

One of the studies involved placing a drop of liquid containing mixed fission products on subjects=forearms, allowing the contamination to dry, and then washing the skin with any of a long list of cleaning agents or chemical solutions. The radioactivity of the contaminated skin area was measured before and after washing to determine decontamination effectiveness. Problems were experienced with test soils because the contamination often failed to adhere to skin.

A second study involved placing a drop of liquid containing zinc bromide, a radiological warfare agent containing a radioactive isotope of tantalum (presumably tantalum-182) on the subjects=palms, after which various decontamination agents were tested.

Another study conducted at Mound Laboratory in Miamisburg, Ohio, involved placing several drops of a solution containing unspecified alpha emitters (presumably polonium-210 and decay products) on the palms of four subjects, allowing the solution to dry, and then testing various detergents as decontamination agents. Measurements of radioactivity were made before and after washing to determine decontamination effectiveness.

These studies pointed to certain commercial products and chemical formulations that could be used for decontaminating human skin or hair. This research was sponsored by the U.S. Atomic Energy Commission.

References

Foster D. Snell, Inc. Removal of Radioactive Contaminants from Human Skin. Final Report, NP-4935, Department of Army, June 15, 1953. Technical Information Service, U.S. Atomic Energy Commission, Oak Ridge, Tennessee.  "

OT-74. Effects of Radium-224 Applied to Skin

EXPERIMENTS WERE CONDUCTED in 1953 at the New York University Hospital and Medical School to evaluate the relative biological effectiveness of the alpha and beta-gamma rays from radium-224 (Ra²²⁴, earlier known as AThorium X@) plaques applied directly to skin. Two types of plaques were studied: a very thin plaque that allowed alpha and beta/gamma radiation to irradiate skin, and a mica-windowed plaque that trapped alpha particles and only irradiated the skin with beta and gamma radiation.

Sealed plaques containing Ra ²²⁴ were applied to arm skin surface of subjects selected from among patients being treated at the University Hospital. The plaques were taped to normal skin areas and allowed to remain in place for 48 hours, after which the skin was examined for visible biological effects.

During the study, 140 plaques were applied to 96 subjects. Seventy-five were alpha plaques and 65 were beta-gamma plaques, usually applied in matched pairs on a given subject. Sixty of the plaques leaked in place and the skin observations in these instances were not used to draw scientific conclusions. Usable observations were obtained from 58 subjects. The alpha plaques produced erythema in about 80 percent of the cases, whereas the beta/gamma plaques produced a discernible erythema in 64 percent of cases. This study was supported by the U.S. Atomic Energy Commission.

References

Witten, V.H., E.W. Brauer, V. Holmstrom, and R. Loevinger. AStudies of Thorium X Applied to Human Skin.@The Journal of Investigative Dermatology. Vol. 21, No. 4, October 1953, pp. 249B257.  "

OT-75. Effects of Strontium-90 and Yttrium-90 on Skin

EXPERIMENTS WERE CONDUCTED in 1954 at the New York University Hospital and Medical School on the biological effects of a pure beta emitter, strontium-90 (Sr⁹⁰), and its decay product, yttrium-90 (Y⁹⁰) when applied directly to skin. The purpose of these experiments was to investigate the dermatologic effects of Sr⁹⁰/Y⁹⁰ beta particles, and to see whether they offered any practical medical advantages over phosphorus-32 (P³²).

Two Sr⁹⁰ applicators of differing dose-rate were constructed using about 10 millicuries of Sr⁹⁰ each on a ceramic disc, which was then covered by a thin (2 millimeters) stainless steel foil soft-soldered to the disc. One applicator was placed 9.5 millimeters from skin and the other was placed 3.2 millimeters from skin. The foil was sufficiently thin to allow the beta particles from Sr⁹⁰ and Y⁹⁰ to penetrate.

Nineteen subjects were identified among patients (mostly outpatients) attending the Hospital=s Skin and Cancer Unit and the Radiotherapy Department. Each subject participated in at least one exposure series (four participated in two series) for a total of 23 series. A total of 195 different sites on normal skin of the subjects upper thighs and lateral buttocks were irradiated using the Sr⁹⁰ application. Absorbed doses were estimated to range from about 85 to 1,540 rads to the local skin areas, although actual values were highly uncertain. The subjects were then observed at various times after irradiation for erythema.

Results showed that erythema occurred as early as 1 day following radiation, followed by pigmentation, and persisted for as long as 102 days. Pigmentation lasted as long as 504 days after irradiation. Other effects observed were papulation (formation of pimple-like skin lumps), induration (hardened portions of skin), and desquamation (shedding of scaly skin) at doses above 684 rads to skin surface. This study was supported by the U.S. Atomic Energy Commission.

References

Witten, V.H., E.W. Brauer, V. Holstrom, and R. Loevinger. AErythema Effects of a Pure Beta Emitter (Strontium-90) on Human Skin.@The Journal of Investigative Dermatology. Vol. 23, No. 4, October 1954, pp. 271B285.  "

OT-76. Topical Absorption Studies Using Radium-224

DURING THE MID-1950s, researchers at the New York University Hospital and Medical School conducted studies on the effect of an electrical current on the absorption of radium-224 (Ra²²⁴) through the skin. Three volunteers participated as subjects. A 1.5-inch square of blotting paper saturated with 12 microcuries of Ra²²⁴ (also known as Athorium X@) was applied to each forearm. One area was subjected to a small electrical current for 20 minutes. After the patches were removed, tissue was excised for analysis.

The results of these studies showed that introduction of an electrical current increased the level of absorption and the biological effect of topically applied Ra²²⁴. The radiation dose to the skin was sufficient to produce erythema (reddening) and pigmentation. These effects were not seen in the absence of an applied electric current. It was believed that this technique could be used clinically in the treatment of various dermatologic lesions and skin cancers. This work was supported by the U.S. Atomic Energy Commission.

References

Fleischnajer, P., and V.H. Witten. Studies of Thorium X Applied to Human Skin. IV. Clinical and Audioradiographic Findings Following the Introduction by Iontophoresis. New York: New York University, Medical School, U.S. Atomic Energy Commission, AECU-3061. Presented at the Sixteenth Annual Meeting of the Society for Investigative Dermatology, June 4B5, 1955, Atlantic City, NJ.  "

OT-77. Effects of Polonium-210 on Skin

A SERIES OF EXPERIMENTS was conducted in 1956 to 1957 at the New York University Hospital and Medical School on the biological effects of a pure alpha emitter, polonium-210 (Po²¹⁰), applied directly to skin. Special polonium plaques were prepared by plating polonium on one side of a nickel disc and electroplating one micrometer of gold over the surface to seal it in place and yet allow alpha particles to freely pass through. The purpose of this study was to investigate further the early biological effects, such as reddening of the skin (erythema), of alpha particle radiation on human skin.

In the first experiment, four Po²¹⁰ plaques of various intensities were each applied to the arm skin of five healthy white males between the ages of 23 and 39 years. Skin surface doses at points of contact were estimated to be 23, 55, 110, and 660 kilorads, respectively, to the layer of skin cells immediately beneath the plaques. Irradiated sites were examined at several times after removal of the plaques for appearance and intensity of skin erythemas.

A second experiment was conducted to determine the smallest dose of Po²¹⁰ alpha radiation that produced a discernible erythema. Seven plaques producing skin surface doses of 12.5, 25, 50, 75, 100, 150, and 200 kilorads, respectively, were applied to arm skin of the same five subjects.

In a third experiment on the same subjects, the time to appearance of erythema was determined as a function of total skin dose.

A fourth experiment was conducted to determine whether the 5.3-MeV (million electron volt) Po²¹⁰ alpha particles were capable of penetrating skin layers to the basement membrane and small blood vessels.

This study showed that a threshold dose for erythema was at 20 kilorads alpha radiation, that erythema appeared 2 to 8 hours after irradiation, that larger doses produced erythema in shorter times, and that erythema was transient. This study was supported by the U.S. Atomic Energy Commission.

References

Witten, V.H., W.S. Wood, and R. Loevinger. AThe Erythema Effects of a Polonium Plaque (An Alpha Emitter) on Human Skin.@The Journal of Investigative Dermatology. Vol. 28, No. 3, March 1957, pp. 199B210.  "

OT-78. Studies of the Transmission of Radioiodine to Infants Through Maternal Breast Milk

DURING THE EARLY 1950s, researchers in the Departments of Medicine, Medical Laboratories and Radiology, University of Tennessee College of Medicine, and the John Gaston Hospital, Memphis, studied the transmission of radioiodine in maternal breast milk to nursing infants. Two black females, ages 22 and 33 years, who were under routine medical surveillance for existing thyroid disease, and their 4-month-old infants, one male and one female, participated as subjects.

The mothers were given 100 microcuries of carrier-free iodine-131 (I¹³¹) by oral administration as part of their routine medical follow-up to evaluate their thyroid function. Iodine-131 activity was measured subsequently in samples of their breast milk and over the thyroid glands of the mothers and infants. Clinical indications required the 22-year-old subject to have a repeat diagnostic thyroid function test 2 months later, for which she received another 100 microcuries of I¹³¹. The infant was placed exclusively on formula, and lactation ceased 6 days later. Radioactivity in the mother=s thyroid and breast milk was measured daily for 7 days after the more recent I¹³¹ administration.

The results of these measurements indicated that iodine concentration in maternal milk was high enough to allow significant uptake in the thyroids of nursing infants, and further indicated that iodine tracer studies in lactating women should be applied cautiously because of potential hazard to the nursing infants=thyroids. This work was supported by the U.S. Atomic Energy Commission.

References

Nurnberger, C.E., and A. Lipscomb. ATransmission of Radioiodine (I¹³¹) to Infants Through Human Maternal Milk.@Journal of the American Medical Association. Vol. 150, No. 14, December 6, 1952, pp. 1,398B1,400.  "

OT-79. Studies of Copper Metabolism Using Copper-64 in Healthy Subjects and Patients with Wilson=s Disease

STUDIES WERE CONDUCTED at the University of Utah College of Medicine in Salt Lake City in approximately 1954 to 1955 on the behavior of elemental copper in normal subjects and in patients with liver disease (Wilson=s disease and alcoholic cirrhosis). Wilson=s disease is a condition involving abnormal metabolism of elemental copper and degeneration of hepatolenticular cells of the liver. The purpose of this study was to learn more about the metabolism and excretion of copper.

One millicurie of copper-64 (Cu⁶⁴) as cupric acetate was administered orally or intravenously to 11 normal, healthy males 25 to 30 years of age; to 4 patients with Wilson=s disease; and to 2 patients with alcoholic cirrhosis of the liver. All individuals were hospitalized in the metabolic ward. A complete physical examination, urine analysis, fecal analysis, and determination of volume of packed red cells, leukocyte count, sedimentation rate, and total plasma copper were carried out on each subject. Urine and stools were collected and analyzed for Cu⁶⁴ content at various times after administration.

This study showed that patients with Wilson=s disease excreted 14 to 44 times more copper than normal subjects during the period of study. The uptake of Cu⁶⁴ by the liver was determined by direct in vivo counting using a mobile body-surface scintillation counter placed over the liver. The uptake of copper in the liver of patients with Wilson=s disease was significantly less than in normal subjects. This work was supported by the National Cancer Institute and the U.S. Atomic Energy Commission.

References

Bush, J.A., J.P. Mahoney, H. Markowitz, C.J. Gubler, G.E. Cartwright, and M.M. Wintrobe. AStudies on Copper Metabolism. XVI. Radioactive Copper Studies in Normal Subjects and in Patients with Hepatolenticular Degeneration.@The Journal of Clinical Investigation. Vol. 34, 1955, pp. 1,766B1,778.  "

OT-80. Studies on Copper Transfer Between Red Blood Cells and Plasma Using Copper-64

A STUDY WAS CONDUCTED in approximately 1955 at the University of Utah College of Medicine in Salt Lake City to determine the rate of movement of small amounts of copper into and out of red blood cells under various conditions.

Copper transfer was studied in one normal subject who was given about 1 millicurie of copper-64 (Cu⁶⁴) as cupric acetate orally, and in four normal male subjects given about 1 millicurie of Cu⁶⁴ intravenously. Blood was drawn and the amount of Cu⁶⁴ in plasma and red blood cells was determined at various times out to 36 or 48 hours after administration.

This study showed that copper bound to plasma albumin is taken up rapidly by red blood cells during circulation in the body. This work was supported by the National Cancer Institute and the U.S. Atomic Energy Commission.

References

Bush, J.A., J.P. Mahoney, C.J. Gubler, G.E. Cartwright, and M.M. Wintrobe. AStudies on Copper Metabolism. XXI. The Transfer of Radiocopper Between Erythrocytes and Plasma.@The Journal of Laboratory and Clinical Medicine. Vol. 47, 1956, pp. 898B906.  "

OT-81. White Blood-Cell Labeling Studies Using Phosphorus-32 in Utah Prisoners

DURING THE LATE 1950s, researchers at the University of Utah College of Medicine in Salt Lake City conducted studies on techniques for labeling white blood cells using phosphorus-32 (P³²). One hundred twenty healthy male inmates, 25 to 50 years old, at the Utah State Prison volunteered to be subjects.

Each subject was intravenously or intramuscularly administered up to 600 microcuries of P³²-labeled diisopropyl-fluorophosphate (DFP³²). A series of 26 blood samples were drawn from each subject over the 22 days following injection. Activity was measured in white blood cells isolated from the samples.

These studies showed that DFP³² was an effective label for counting white cells and validated the procedures used. The studies also showed that use of DFP³² did not produce toxic side effects and did not damage white cells. This work was supported by the U.S. Public Health Service. The assistance of the University of Utah Radiobiology Laboratory on this project was funded by the U.S. Atomic Energy Commission (AEC).

References

Athens, J.W., A.M. Mauer, H. Ashenbrucker, G.E. Cartwright, and M.M. Wintrobe. ALeuko-kinetic Studies: I. A Method for Labeling Leukocytes with Diisopropylfluorophosphate (DFP³²).@Blood: The Journal of Hematology. Vol. 14, No. 4, April 1959, pp. 303B333.  "

OT-82. Granulocyte Studies Using Phosphorus-32 in Utah Prisoners

DURING THE LATE 1950s, researchers at the University of Utah College of Medicine in Salt Lake City conducted studies on the relationship between the distribution of granulocytes (a type of white blood cell) and the circulating pool of granulocytes.

The 45 healthy inmates, 20 to 50 years old, at Utah State Prison who volunteered for the granulocyte study, received diisopropylfluorophos-phate (DFP³²) labeled with phosphorus-32 (P³²). After blood was drawn from the subjects, the granulocytes were labeled with DFP³² and infused into the original donor. Amounts of administered activity were not reported. Labeled granulocytes were counted and blood samples drawn after the infusion.

These studies showed that granulocytes were distributed in a total blood pool consisting of separate circulating and marginal pools. The study also provided estimates of the size of these pools. This work was supported by the U.S. Public Health Service. The University of Utah=s radiobiology studies were supported in part by the U.S. Atomic Energy Commission.

References

Athens, J.W., S.O. Raab, O.P. Haab, A.M. Mauer, H. Ashenbrucker, G.E. Cartwright, and M.M. Wintrobe. ALeukokinetic Studies. III. The Distribution of Granulocytes in the Blood of Normal Subjects.@Journal of Clinical Investigation. Vol. 40, 1961, pp. 159B164.  "

OT-83. White Blood-Cell Production Studies Using Phosphorus-32

DURING THE EARLY 1960s, investigators at the University of Utah in Salt Lake City conducted studies to learn more about the production and fate of granular leukocytes (white blood cells) in humans. The subjects were 109 healthy, male inmates of the Utah State Prison between the ages of 19 and 54 years.

The study involved drawing 400 milliliters of blood from each study participant; labeling the granulocytes with the compound diisopropyl-fluorophosphate (DFP), which contained phosphorus-32 (P³²) tracer; and returning the blood to the donor. Alternatively, the DFP³² was intravenously injected directly into the subjects to label circulating granulocytes. At subsequent times, blood was drawn and counted for P³² activity to determine the production and kinetics of blood granulocytes.

The study was repeated on the same subjects about 1 month later to determine the biological variation between individuals or within the same individual over time. The amount of P³² tracer administered to each subject was not stated.

The study provided new information on the distribution of granulocytes and their rate of disappearance from circulation. Times required for granulocyte production and the rates of cell maturation were also determined. This work was supported by the National Institute of Arthritis and Metabolic Diseases. The University of Utah=s radiobiology studies were supported in part by the U.S. Atomic Energy Commission.

References

Boggs, D.R., J.W. Athens, G.E. Cartwright, and M.M. Wintrobe. AMasked Granulocytosis.@Proceedings of the Society for Experimental Biology and Medicine.Vol. 118, 1965, pp. 753B755.

Cartwright, G.E., J.W. Athens, and M.M. Wintrobe. AThe Kinetics of Granulopoiesis in Normal Man.@Blood: The Journal of Hematology. Vol. 24, No. 6, 1964, pp. 780B803.

Wintrobe, M.M. Hematology, the Blossoming of a Science. Philadelphia: Lea and Febiger, 1985.  "

OT-84. Study of Copper Metabolism Using Copper-64

DURING THE EARLY 1960s, basic studies on copper metabolism in normal subjects were conducted at the University of Utah College of Medicine in Salt Lake City. The purpose of these studies was to determine total serum copper (copper associated with red blood cells); copper in the liver, brain, kidneys, heart, spleen, and whole-body; and rate of copper excretion in urine and stool. The subjects consisted of 135 men and 100 women, including 72 normal pregnant women (in their third trimester). This study involved the analysis of stable copper as well as radioactive copper tracer in a few subjects.

Two or more of the subjects were administered copper-64 (Cu⁶⁴) either orally or intravenously, although the exact number given radioactive copper and the amounts ingested or injected is not known. Stable copper was determined using spectrophotometric methods; radioactive copper was determined by standard counting.

This study showed that about 0.33 of the 2 to 5 milligrams of copper ingested daily in the diet of the normal subjects was absorbed. Most copper was excreted in the bile to the bowel. Only a small fraction was excreted in urine. This work was supported by the National Institute of Arthritis and Metabolic Diseases. The University of Utah=s radiobiology studies were supported in part by the U.S. Atomic Energy Commission.

References

Cartwright, G.E., and M.M. Wintrobe. ACopper Metabolism in Normal Subjects.@American Journal of Clinical Nutrition. Vol. 14, JanuaryBJune 1964, pp. 224B232.  "

OT-85. Blister Studies Using Phosphorus­32 in Utah Prisoners

DURING THE EARLY 1960s, researchers at the University of Utah College of Medicine in Salt Lake City conducted studies on the cellular concentration of white blood cells in blisters using diisopropylfluorophosphate (DFP³²) labeled with phosphorus-32 (P³²).

Twenty-eight healthy male inmates of the Utah State Prison ranging in age from 20 to 44 years participated as subjects. Each was administered an unstated amount of DFP³² to label white blood cells in circulating blood. Blister formation was then induced on the subject=s forearm and inflammation was generated by injecting a heat-killed culture of staphylococci bacteria into the blister. Fluid was drawn from the blister and DFP³²-labeled white cells were counted.

These studies showed extreme variation between subjects. The studies also showed that different types of white cells increased in the blister fluid at different rates. This work was supported by the U.S. Public Health Service. The University of Utah=s radiobiology studies were supported in part by the U.S. Atomic Energy Commission.

References

Boggs, D.R., J.W. Athens, O.P. Haab, S.O. Raab, G.E. Cartwright, and M.M Wintrobe. AInduced Inflammatory Exudates in Normal Man.@American Journal of Pathology. Vol. 44, No. 1, January 1964, pp. 61B71.  "

OT-86. Comparative Metabolism of Radium-226 and Strontium-85

DURING1962 TO 1963, scientists at the Radiobiology Division of University of Utah in Salt Lake City conducted a study to determine the early retention and excretion of radium-226 (Ra²²⁶) and strontium-85 (Sr⁸⁵) in man.

An 80-year-old man with an epidermoid carcinoma on his facial skin was given 10 micro-curies of Sr⁸⁵ and 1.5 microcuries of Ra²²⁶ in normal saline solution by intravenous injection. The radioactivity retained in the subject was counted periodically in the whole-body counter. Samples of blood, urine, and feces were collected and assayed for radioactivity.

Fifty-eight days after the injection, the subject retained 21 percent of the injected strontium (corrected for radioactive decay). Measurements made at the subject=s time of death, 141 days postinjection, showed that Ra²²⁶ retention was only 6.5 percent of the administered activity, with 5.2 percent in bone plus 1.3 percent in soft tissue. This research was supported by the U.S. Atomic Energy Commission.

References

Mays, C.W., R.D. Lloyd, W.R. Christensen, D.R. Atherton, G.S. Pitchford, and W.W. Parmley. ARadium Studies in a Man Soon After Injection.@Research in Radiobiology: Annual Report of Work in Progress on the Chronic Toxicity Program.Salt Lake City: University of Utah, Radiobiology Division of the Department of Anatomy, University of Utah College of Medicine, September 30, 1962, pp. 71B77.

Mays, C.W., R.D. Lloyd, W.R. Christensen, D.R. Atherton, and G.S. Pitchford. ARadium Metabolism in a Man.@Research in Radiobiology: Annual Report of Work in Progress on the Chronic Toxicity Program.Salt Lake City: University of Utah, Radiobiology Division of the Department of Anatomy, University of Utah College of Medicine, March 31, 1963, p. 224.  "

OT-87. Total-Body Counter Calibration Using Cesium-132 and Potassium­42

FROM JANUARY TO OCTOBER 1963 researchers at the Radiobiology Division of University of Utah in Salt Lake City used subjects with known amounts of radioactivity in their bodies to calibrate the whole-body counter. After fasting, four female and six male healthy, fasting volunteers were given 0.1 microcurie of cesium-132Bchloride (Cs¹³²Cl) orally. Two subjects were counted immediately after ingestion to establish a baseline by which the change in the counting rate could be determined. Counting was repeated periodically for an additional 50 hours. Total excreta collections were made and assayed for Cs¹³². Nine months later, the same four females and six males (with one substitution) were orally administered 1 microcurie of potassium-42 (K⁴²), and the same protocol was followed.

This research helped calibrate the whole-body counter for later measurements of radioactive fallout in Utah residents from atomic weapons testing in Nevada. This research was sponsored in part by the Division of Radiological Health, Bureau of State Services of the U.S. Public Health Service. The assistance of the University of Utah Radiobiology Laboratory on this project was funded by the U.S. Atomic Energy Commission (AEC).

References

Lloyd, R.D. AHuman Total-Body Counter Calibration.@FromResearch in Radiobiology: Annual Report of Work in Progress on the Chronic Toxicity Program [to the U.S. Atomic Energy Commission under Contract AT (11-1)-119]. Salt Lake City: University of Utah, Radiobiology Division of the Department of Anatomy, University of Utah College of Medicine, March 31, 1964, pp. 186B198.  "

OT-88. Study of Cortisone-Induced Granulocytosis Using Phosphorus-32BLabeled Diiso-propylfluorophosphate in Utah Prisoners

RESEARCHERS AT the University of Utah College of Medicine in Salt Lake City conducted a study between 1964 and 1966 to find the mechanism by which steroids induce granulocytosis (a condition characterized by more than the normal number of white blood cells in the circulating blood).

Nine inmates between the ages of 23 and 40 from the Utah State Prison participated in this study. Each inmate had 300 to 500 milliliters of blood drawn and their granulocytes (a type of white blood cell) were then incubated with diisopropylfluorophosphate (DFP) labeled with phosphorus-32 (P³²) in tracer amounts. The cells were then returned to the corresponding donor. The amount of the P³² administered to each subject was not stated.

The participants were then injected intravenously with 200 milligrams of cortisol (a steroid) to induce granulocytosis. Inflammatory lesions were produced on the skin to assess the effect of the steroids on the flow of granulocytes to the skin. The accumulation of granulocytes in the inflammation was determined before and, at various times, after the administration of the steroid.

Results of this study helped researchers understand that granulocytosis is produced by an increased inflow of marrow granulocytes into the blood. This experiment was a continuation of an earlier study by the University of Utah that examined the production of granulocytes and was supported by the National Institute of Arthritis and Metabolic Diseases, and the National Institutes of Health. The University of Utah=s radiobiology studies were supported in part by the U.S. Atomic Energy Commission.

References

Bishop, C.R., J.W. Athens, D.R. Boggs, H.R. Warner, G.E. Cartwright, and M.M. Wintrobe. AA Non-Steady-State Kinetic Evaluation of the Mechanism of Cortisone-Induced Granulocytosis.@The Journal of Clinical Investigation. Vol. 47, 1968, pp. 249B260.  "

OT-89. Cesium-137 and Rubidium-83 Metabolism in Healthy Subjects and Subjects with Muscular Dystrophy

BETWEEN 1965 AND 1972, researchers in the Departments of Anatomy, Medicine, and Radiological Health at the University of Utah in Salt Lake City conducted a series of studies of the metabolism of cesium-137 (Cs¹³⁷) and rubidium-83 (Ru⁸³) in healthy individuals and in persons with muscular dystrophy. Estimates were made of the biological retention half-time of Cs¹³⁷ from environmental radioactive fallout, based on measured body burdens and excretion rates.

Participating in this study were 39 healthy individuals: 5 infants, ages 17 to 143 days; 5 children, ages 5 to 10 years; 23 adults, ages 21 to 52 years, including 6 pregnant females; and 3 children, ages 4 to 11, with Duchenne muscular dystrophy.

The average values for Cs¹³⁷ half-time in the healthy subjects was found to increase with age from 19 days in infants to 95 days in adults. The Cs¹³⁷ half-time in the six pregnant females averaged 45 days, confirming earlier reports of increased Cs¹³⁷ excretion during pregnancy. The average half-time for the dystrophic children was 18 days, about a third of that expected in healthy children.

Between 1968 and 1972, the initial investigation of Cs¹³⁷ metabolism in persons with muscular dystrophy was extended to (1) establish normal values for cesium and rubidium metabolism as a function of age for control subjects; (2) correlate observed metabolic differences between control and dystrophic subjects with the degree of disease severity; (3) compare Duchenne dystrophy with other muscle diseases; and (4) search for metabolic differences between female controls and female genetic carriers of Duchenne dystrophy. A total of 38 persons of various ages participated in the extended study. Seventeen subjects (14 males, 3 females; ages 5 to 61 years) had muscle disease, and 21 subjects (9 males, 12 females; ages 4 to 80 years, including at least 1 of the investigators) were normal volunteer subjects. About 1 microcurie Cs¹³⁷ and 6 microcuries Ru⁸³ as a double tracer were administered orally to each subject over 18 years of age. Younger subjects received half these amounts. Samples of blood, feces, and urine were collected for analysis, regularly from some subjects and intermittently from others. Cesium-137, and especially Ru⁸³ retention, was notably lower among the dystrophic subjects than among the healthy volunteers, including the known or suspected carriers of the Duchenne gene.

The results supported the hypothesis that muscular dystrophy is associated with a cell membrane defect, resulting in altered permeability. These studies were supported by the National Institutes of Health and the U.S. Atomic Energy Commission.

References

Lloyd, R.D., W.S. Zundel, C.W. Mays, W.W. Wagner, and R.C. Pendleton. AEnhanced Cs¹³⁷ Elimination in Pregnant and Dystrophic Humans.@Radiation Research. Vol. 27, 1966, p. 548.

Lloyd, R.D., W.S. Zundel, C.W. Wagner, and R.C. Pendleton. AShort Cesium-137 Half-Time in Patients with Muscular Dystrophy.@Nature. Vol. 220, December 7, 1968, pp. 1,029B1,031.

Lloyd, R.W., C.W. Mays, W.S. Zundel, F.H. Tyler, D.H. Taysum, R.C. Pendleton, and H.H. Hupf. Cesium, Rubidium, and Potassium Metabolism: Studies of Muscle Seeking Radionuclides. Salt Lake City, UT: University of Utah,Radiobiology Division of the Department of Anatomy, College of Medicine. December 1968, pp. 2B39.

Lloyd, R.W., C.W. Mays, S.S. McFarland, W.S. Zundel, and F.H. Tyler. ARb⁸³ and Cs¹³⁷ Metabolism in Persons Affected by Muscle Disease.@Salt Lake City, UT: University of Utah, the Radiobiology Division of the Department of Anatomy: University of Utah, College of Medicine. October 1972.

Lloyd, R.D., C.W. Mays, S.S. McFarland, W.S. Zundel, and F.H. Tyler. AMetabolism of Rb⁸³ and Cs¹³⁷ in Persons with Muscle Disease.@Radiation Research. Vol. 54, No. 3, June 1973, pp. 463B478.

Mays, C.W., W.S. Zundel, R.D. Lloyd, W.W. Wagner, and R.C. Pendleton. APotassium and Cs¹³⁷ Studies in Patients with Muscular Dystrophy.@Radiation Research. Vol. 31, 1967, p. 538.  "

OT-90. Study of Granulocyte Kinetics During Endotoxin-Induced Granulocytosis Using Phosphorus-32

BETWEEN 1969 AND 1971, investigators at the University of Utah College of Medicine in Salt Lake City and the Salt Lake Veterans Administration Hospital conducted a study to determine whether endotoxins (bacteria toxins) liberated into surrounding medium produced granulocytosis (a condition characterized by more than the normal number of granulocytes, a type of white blood cell in the circulating blood).

Eighteen men from the Utah State Prison between the ages of 20 and 36 years volunteered as participants in this study. The subjects had 300 to 500 milliliters of blood drawn. The granulocytes were separated out and then incubated with diisopropylfluorophosphate (DFP) labeled with phosphorus-32 (P³²) tracer; the cells were then injected into the corresponding donor. The amount of P³² tracer administered to each subject was not stated. Granulocyte counts and specific activity measurements were made before and after bacterial endotoxin (Salmonella or Pseudomonas) was given intravenously to 12 subjects; in this study, both radioactive materials and biological toxins were administered to some subjects. The remaining six subjects served as controls and received DFP³², but no endotoxin.

Results from this study showed that a moderate dose of bacterial endotoxin resulted in an increase in the granulocyte count. This experiment was a continuation of an earlier University of Utah study that described the changes in granulocyte inflow and outflow rates before, during, and after steroid-induced granulocytosis. This study was supported by the National Institute of Arthritis and Metabolic Diseases and the National Institutes of Health. The University of Utah=s radiobiology studies were supported in part by the U.S. Atomic Energy Commission.

References

Ostlund, R.E., C.R. Bishop, and J.W. Athens. AEvaluation of Non-Steady-State Neutrophil Kinetics During Endotoxin-Induced Granulocytosis.@In The Proceedings of the Society for Experimental and Biological Medicine. Vol. 137, 1971, pp. 763B767.  "

OT-91. Study of the Transfer of Iron-59 and Iodine-131 Between Mother and Fetus

RESEARCH WAS CONDUCTED during the period 1967 to 1968 at Vanderbilt University School of Medicine in Nashville, Tennessee, on the biological transfer and distribution of radionuclides between mother and fetus. The purpose of this study was to determine the magnitude of the hazard to the fetus from intakes of radionuclides by the mother. The five subjects chosen for this study were pregnant women already scheduled for therapeutic abortions. The gestational ages of the fetuses ranged from 11 to 22 weeks.

Each subject was administered 10 microcuries Fe⁵⁹ intravenously as ferrous citrate and 50 microcuries of iodine-131 (I¹³¹) orally as sodium iodide as tracers 18 hours prior to the scheduled abortion. The amounts of iron-59 (Fe⁵⁹) and I¹³¹ in the total aborted fetus were then determined. Samples of the fetal tissues were studied to determine the biological distributions of Fe⁵⁹ and I¹³¹ among the different organs and tissues, the amniotic fluid, and the umbilical cord.

These data provided information about the fraction of activity passing from mother to fetus during the first 18 hours after radionuclide administration, and also the data on concentrations of I¹³¹ and Fe⁵⁹ in fetal tissues. Eighty percent of the Fe⁵⁹ was deposited in the fetal liver and 65 percent of the I¹³¹ was deposited in the fetal thyroid. This work was supported in part by the U.S. Atomic Energy Commission.

References

Dyer, N.D., A.B. Brill, S.R. Glasser, and D.A. Goss. AMaternal-fetal Transport and Distribution of Fe⁵⁹ and I¹³¹ in Humans.@American Journal of Obstetrics and Gynecology. Vol. 103, January 15, 1969, pp. 290B296.

Dyer, N.D., and A.B. Brill. AFetal Radiation Dose from Maternally Administered Fe⁵⁹ and I¹³¹.@In Proceedings of the Ninth Annual Hanford Biology Symposium at Richland, Washington, May 5B8, 1969, edited by M.R. Sikov and D.D. Mahlum, pp. 73B87. Sponsored by Battelle Memorial Institute Pacific Northwest Laboratory and the U.S. Atomic Energy Commission. December 1969.  "

OT-92. Metabolism Studies Using Strontium-85 and Calcium-47

IN THE EARLY 1970s, researchers at the Veterans Administration Hospital, Hines, Illinois, conducted studies on the uptake, retention, and excretion of strontium using strontium-85 (Sr⁸⁵), strontium-90 (Sr⁹⁰), and calcium-47 (Ca⁴⁷). Ambulatory patients in the hospital metabolic research ward participated as subjects.

Each subject was orally or intravenously administered tracer amounts of Sr⁸⁵ and Ca⁴⁷. Strontium-90 intake through normal diet was measured by low-level beta counting. Activity was measured in plasma, urine, and feces; the activity was then analyzed in conjunction with administration of stable strontium, stable calcium (high and low intake), phosphate (high intake), vitamin-D, aluminum phosphate gel, ammonium chloride, diuretics, magnesium, stable strontium, and various chelating agents.

The results of these studies provided considerable data on the metabolism of strontium in humans and on the effects of certain chemicals on strontium metabolism. This work was supported by the U.S. Atomic Energy Commission.

References

Spencer, H., L. Kramer, and J. Samachson. AEffect of Stable Strontium on Sr⁸⁵ Absorption and Excretions in Man.@Radiation Research. Vol. 47, 1971, p. 281.

Spencer, H., L. Kramer, and J. Samachson. AMetabolism and Removal of Radiostrontium in Man.@In Proceedings of the Symposium Biomedical Implications of Radiostrontium Exposure. Berkeley, CA: University of California, Radiobiology Laboratory, April 1972, pp. 31B51.  "

OT-93. Measuring Extracellular Fluid Using Sodium-24

DURING THE LATE 1940s AND IN 1950, researchers in the Department of Internal Medicine, Bowman Gray School of Medicine, Wake Forest University in Winston-Salem, North Carolina, conducted studies to measure extracellular fluid space using radioactive sodium-24 (Na²⁴).

Twenty patients with a variety of clinical conditions participated as subjects. Each received an intravenous injection of about 2 to 3 microcuries of Na²⁴ per kilogram of body weight. Radioactivity measured in a subsequently drawn blood sample was used to determine fluid space. The results were compared with results obtained by similar measurements using nonradioactive thiocyanate.

These studies showed that radiosodium was a highly accurate means of measuring fluid space. However, the wide variation between Na²⁴ and thiocyanate measurements in diseased individuals suggested that both methods should be applied in clinical investigations. This work was supported by the U.S. Atomic Energy Commission.

References

Aikawa, J.K. AThe Significance of the Radiosodium Space in Human Disease.@Southern Medical Journal. Vol. 44, No. 7, July 1951, pp. 654B661.  "

OT-94. Potassium Studies in Diseased Patients Using Potassium-42

DURING THE EARLY 1950s, researchers at Wake Forest College and North Carolina Baptist Hospital in Winston-Salem, North Carolina, conducted studies to determine the total-body content of elemental potassium in diseased patients using potassium-42 (K⁴²) The subject pool consisted of 39 male and 30 female hospitalized patients ranging in age from 14 to 78 years, and 6 healthy individuals.

Each subject underwent up to three measurements of body potassium by intravenous administration of 100 microcuries of K⁴² and subsequent activity counting in urine samples.

These studies showed that the potassium levels in diseased subjects were similar to or lower than the levels in normal subjects. The lower levels in some patients suggested a potassium deficiency. This work was supported by the U.S. Atomic Energy Commission and partly by the American Heart Association.

References

Aikawa, J.K., J.H. Felts, Jr., M.P. Tyor, G.T. Harrell, and E.L. Rhoades. AThe Exchangeable Potassium Content in Disease States.@The Journal of Clinical Investigation. Vol. 31, July 1952, pp. 743B749.  "

OT-95. Potassium Studies in Women Using Potassium-42

DURING THE EARLY 1950s, researchers at the Department of Internal Medicine, Bowman Gray School of Medicine, Wake Forest University in Winston-Salem, North Carolina, conducted studies on body potassium content in women using potassium-42 (K⁴²). The purpose of this study was to compare total-body potassium content in women compared to content in previously studied normal healthy men.

Twenty healthy females, comprising nurses, medical students, and laboratory technicians, ranging in age from 19 to 32 years participated as subjects. Each subject was intravenously administered 100 microcuries of K⁴² and activity was measured in subsequently collected urine samples.

The studies showed that the level of exchangeable potassium in the young female subjects was considerably lower than the levels observed in young men, apparently due to the relatively greater amount of fat in the women. This work was supported by the U.S. Atomic Energy Commission and partly by the American Heart Association.

References

Aikawa, J.K., G.T. Harrell, and B. Eisenberg AThe Exchangeable Potassium Content of Normal Women.@Journal of Clinical Investigation. Vol. 31, April 1952, pp. 367B369.  "

OT-96. Sodium Volume Studies in Diseased Patients Using Sodium­24

DURING THE EARLY 1950s, researchers at the North Carolina Baptist Hospital and at the Bowman Gray School of Medicine at Wake Forest College in Winston-Salem, North Carolina, conducted research on body sodium in diseased patients using sodium-24 (Na²⁴). The purpose of the study was to compare the volumes of fluid available for dilution of thiocyanate and radiosodium ions in diseased individuals.

Twenty-six hospitalized patients and three normal medical students participated as subjects. Each was intravenously administered 150 microcuries of Na²⁴ and activity was measured in subsequently drawn blood samples. Thiocyanate measurements were accomplished without administration of any radioactivity.

The studies showed almost identical thiocyanate and sodium volumes in normal subjects, but different volumes in diseased subjects. This work was supported by the U.S. Atomic Energy Commission.

References

Aikawa, J.K., and E. Rhoades. AComparison of the Thiocyanate and Radiosodium Spaces in Disease States.@The American Journal of the Medical Sciences. Vol. 224, 1952, pp. 632B637.  "

OT-97. Study of Potassium Metabolism in Hyperthyroidism Using Potassium-42

DURING THE EARLY 1950s, researchers at the Department of Internal Medicine, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina, conducted studies on the metabolism of potassium in subjects with untreated hyperthyroidism.

Thirteen hospitalized men and women ranging in age from 21 to 68 years participated in the study. Each subject received an intravenous injection of 100 microcuries of potassium-42 as potassium chloride. Urine samples were collected 24 hours after injection and the measured radioactivity was used to calculate body potassium content.

These studies showed that potassium levels were lower in untreated hypothyroid males than in normal males, but that the levels in untreated hyperthyroid females were similar to normal females. This gender difference was attributed to the dissimilarity in body composition and muscle mass normally found between males and females. This work was supported by the U.S. Atomic Energy Commission and by a grant from the American Heart Association.

References

Aikawa, J.K. AIsotopic Studies of the Body Potassium Content in Thyrotoxicosis.@In Proceedings of the Society for Experimental Biology and Medicine. Vol. 84, No. 3, December 1953, pp. 594B596.  "

OT-98. Studies of Potassium Metabolism in Diabetes Using Potassium-42 Tracer

DURING THE EARLY 1950s, researchers at Wake Forest College in Winston-Salem, North Carolina, and North Carolina Baptist Hospital conducted studies on potassium metabolism in diabetic patients. Forty-two male and female hospitalized patients ranging in age from 18 to 78 years participated as subjects.

One hundred microcuries of radioactive potassium-42 (K⁴²) were administered intravenously to the subjects. Twenty subjects received a single injection and 22 subjects received 2 to 4 injections. Measurements of K⁴² in urine specimens collected after each injection were used to calculate the exchangeable body content of potassium. Fifteen subjects who received multiple injections also received oral supplements of nonradioactive (stable) potassium beginning 1 week after the K⁴² injection.

The studies showed that potassium values were significantly lower in diabetic males compared to normal males, but not significantly different between diabetic and normal females. The studies also showed that a potassium deficit could be correlated with the relative adequacy of control of the disease and that a deficit could be regulated by administration of an oral potassium supplement. This work was supported by the American Heart Association and by the U.S. Atomic Energy Commission.

References

Aikawa, J.K., J.H. Felts, Jr., and G.T. Harrell, Jr. AIsotopic Studies of Potassium Metabolism in Diabetes.@Journal of Clinical Investigation. Vol. 32, 1953, pp. 15B21.  "

OT-99. Iron Absorption Studies Using Iron-55 and Iron-59 in Normal Subjects and Mental Patients

STUDIES CONDUCTED in the 1950s by medical scientists at the University of Washington, Seattle used a double isotope technique to improve the understanding of the way in which the human body absorbs and metabolizes iron.

The first in the related series of studies involved injections of iron-55 (Fe⁵⁵) and iron-59 (Fe⁵⁹) in various animals and 12 normal human subjects. In human subjects, the amount of Fe⁵⁵ varied between 50 and 100 microcuries with stable iron carrier (100 and 500 milligrams). Approximately 1 microcurie of Fe⁵⁹ was given intravenously as ferrous citrate. This study showed that both the size of iron stores and the rate at which red blood cells formed influenced iron absorption. The larger the iron stores, the less iron was absorbed, whereas the greater the red cell production, the greater the amount of iron was absorbed.

In another study, 20 patients with normal iron metabolism history, 19 anemic patients, 19 with abnormal red blood-cell counts, and 5 with iron storage disease were used as subjects to measure iron absorption. Some of the normal hematological subjects were mental patients. The absorption of iron was studied in patients who were given a test meal containing 50 microcuries Fe⁵⁵ in the form of ferric chloride added halfway through the meal. After the meal, the subjects were also administered Fe⁵⁵ as ferric chloride by intravenous injection to compare iron absorption after administration of iron by separate routes of intake. A double isotope technique using Fe⁵⁵ and Fe⁵⁹ was employed to measure absorption of iron from food. The absorption of iron from food by both normal and iron deficient subjects was slower than that seen when iron salts alone were given. Supplemental ascorbic acid diminished this difference.

The study also concluded that anemia was not an important factor in the regulation of iron absorption. Other observations were also reported with regard to iron absorption in cases of abnormal red blood-cell counts and anemia. This research was supported by the U.S. Atomic Energy Commission.

References

Bothwell, T.H., G. Pirzio-Biroli, and C.A. Finch. AIron Absorption I. Factors Influencing Absorption.@The Journal of Laboratory and Clinical Medicine. Vol. 51, No. 24, 1958, pp. 24B36.

Pirzio-Biroli, G., T.H. Bothwell, and C.A. Finch. AIron Absorption II. The Absorption of Radioiron Administered with a Standard Meal in Man.@The Journal of Laboratory and Clinical Medicine. Vol. 51, No. 1, 1958, pp. 37B48.

Letter. C.A. Finch to S. Marks. July 17, 1984. Pacific Northwest Laboratory General Human Subjects, Box Alan Rither, PNL-9055-DEL (CIC #701610, bate 8756).  "

OT-100. Study of Iron Turnover Rates Using Iron-55 in Men, and Nonmenstruating and Menstruating Women

A STUDY WAS CONDUCTED between 1954 and 1958 by medical scientists at the University of Washington, Seattle, to investigate total-body iron turnover rates. The study involved 6 adult men, 12 adult nonmenstruating women, and 6 adult menstruating women.

All subjects were mental patients at the Northern State Hospital in Sedro-Woolley, Washington. The subjects were selected for study because of their good health, their normal hematologic values, and the absence of history of abnormal blood loss or anemia. Iron-55 (Fe⁵⁵) was injected intravenously to each patient as Fe⁵⁵ citrate in dosages of 100 microcuries. Blood samples were drawn 2 months after injection, and at 4-month intervals thereafter over a period of 46 to 54 months, and analyzed for Fe⁵⁵ activity.

This study showed that red cell iron turnover over a 4-year period is 0.61 milligram per day in men, 0.64 milligram per day in nonmenstruating women, and 1.22 milligrams per day in menstruating women. The research was supported by the and the U.S. Public Health Service and the U.S. Atomic Energy Commission.

References

Finch, C.A., and B. Loden. ABody Iron Exchange in Man.@The Journal of Clinical Investigation. Vol. 38, No. 2, 1959, pp. 392B396.

Letter. C.A. Finch to S. Marks. July 17, 1984. Pacific Northwest Laboratory General Human Subjects, Box Alan Rither, PNL-9055-DEL (CIC #701610, bate 8756).  "

OT-101. Study of Cooley=s Anemia in Children Using Chromium-51 and Iron-59

A STUDY WAS CONDUCTED in 1955 by medical scientists at the University of Washington, Seattle and the Department of Research at Children=s Hospital in Los Angeles on four children, two of whom were siblings, with Cooley=s anemia, a genetic blood disorder.

The children, ages 4, 6, 9, and 13 were given iron-59 (Fe⁵⁹) and chromium-51 (Cr⁵¹). About 20 microcuries, or 0.5 microcurie per estimated kilogram of body weight, of Fe⁵⁹ as ferrous citrate were administered intravenously to the subjects to determine plasma iron turnover and red blood-cell utilization. Chromium-51 was administered intravenously to label red blood cells and to determine red cell survival times. The amount administered to each subject was not stated.

The study provided information on the underlying defects in children with the disease and showed that the severity of the anemia was largely related to a defect in the production of red cells, not in total hemoglobin synthesis. The research was supported by grants from the U.S. Public Health Service, the National Institutes of Health, and the U.S. Atomic Energy Commission.

References

Sturgeon, P., and C.A. Finch. AErythrokinetics in Cooley=s Anemia.@Blood: The Journal of Hematology. Vol. 12, 1957, pp. 64B73.

Letter. C.A. Finch to S. Marks. July 17, 1984. Pacific Northwest Laboratory General Human Subjects, Box Alan Rither, PNL-9055-DEL (CIC #701610, bate 8756).  "

OT-102. Study of Red Blood-Cell Production Using Iron-59

IN THE LATE 1960s, researchers at the University of Washington, Seattle and the Universidad Nacional Mayor de San Marcos in Lima, Peru, investigated the effects of altitude changes on erythropoiesis (red blood-cell formation), iron absorption, and oxygen binding at high altitudes.

Seven healthy male Lima residents, at sea level, between the ages of 18 and 30 years, were transported to Morococha (elevation 4,530 meters) for observation. Conversely, six healthy male Morococha residents, between the ages of 20 and 39 years, were transported to Lima for observation. While at the atypical altitude, each subject received an intravenous injection of 2 to 5 microcuries of iron-59 (Fe⁵⁹) citrate. Later, each subject received 15 microcuries of Fe⁵⁹ intravenously. Blood and urine samples were taken to measure erythropoietin (a hormone that stimulates red blood-cell production), oxygen binding, and iron absorption levels.

The study found that erythropoiesis is stimulated by ascent to high altitudes and suppressed upon descent to lower altitudes. This study was supported by the U.S. Public Health Service and the U.S. Atomic Energy Commission.

References

Faura, J., J. Ramos, C. Reynafarje, E. English, P. Finne, and C. Finch. AEffect of Altitude on Erythropoiesis.@Blood: The Journal of Hematology. Vol. 33, No. 5. 1969, pp. 668B676.

Lenfant, C., J. Torrance, E. English, C. Finch, C. Reynafarje, J. Ramos, and J. Faura. AEffect of Altitude on Oxygen Binding by Hemoglobin and on Organic Phosphate Levels.@The Journal of Clinical Investigation. Vol. 47, No. 12, December 1968, pp. 2,652B2,656.

Cook, J.D. ASummary of ResultsCPeru Study.@Seattle: University of Washington, 1969. Hanford Records Holding Area, DOE-RL Procurement Division Records, Box 024223, RLHTS94-0081, Contract AT (45-1) 2048.  "

OT-103. Sodium Volume Studies in Children and Adults Using Sodium-24

BETWEEN 1949 AND 1951, researchers at Washington University in St. Louis; St. Louis Children=s Hospital; and St. Louis Maternity Hospital conducted studies on sodium space in children and adults using sodium-24 (Na²⁴). The term Aspace@refers to the volume within which sodium is distributed in the body.

Thirty-seven male or female infants and children ranging in age from one day to 14 years, and 19 adult males ranging in age from 22 to 34 years participated as subjects. Each subject was intravenously administered 1.0 to 1.5 microcuries of Na²⁴ per kilogram of body weight. Blood samples were drawn 1.75 to 4.5 hours after injection and analyzed for activity. The total estimated dose was between 0.11 and 0.17 roentgen equivalent physical in the adult. Urine samples were also collected and analyzed.

The results of these studies showed that the volume of fluid occupied by sodium declines in relation to body weight as growth proceeds. This work was supported by the Children=s Research Foundation and the U.S. Atomic Energy Commission.

References

Perley, A., G.B. Forbes, and M.M. Pennoyer ADetermination of Sodium >Space=in Infants, Children, and Adults.@The Journal of Pediatrics. Vol. 38, JanuaryBJune 1951, pp. 299B305.  "

OT-104. Estimates of Total-Body Sodium in Infants and Children Using Sodium-24

DURING THE EARLY 1950s, researchers at the Department of Pediatrics, Washington University School of Medicine in St. Louis, and St. Louis Children=s Hospital conducted studies using sodium-24 (Na²⁴) to determine the amounts of total-body sodium in children and infants.

Twenty-one hospitalized patients ranging in age from 2 weeks to 14 years participated as subjects. Each subject was intravenously administered 1.0 to 1.5 microcuries of Na²⁴ per kilogram of body weight. Activity was measured in subsequently collected urine and blood samples.

The results of these studies showed that sodium levels are high in infants and gradually decline with age until adult levels are reached. The studies also showed that sodium is related to body weight in a predictable way. This work was supported by the U.S. Atomic Energy Commission.

References

Forbes, G.B., and A. Perley. AEstimation of Total-Body Sodium by Isotopic Dilution: II. Studies on Infants and Children: An Example of a Constant Differential Growth Ratio.@Journal of Clinical Investigation. Vol. 30, June 1951, pp. 566B574.  "

OT-105. Total-Body Sodium Studies Using Sodium-24

DURING 1950 TO 1951, researchers at Washington University in St. Louis, and St. Louis Children=s Hospital, St. Louis, Missouri, conducted studies to determine total-body sodium in adults using sodium-24 (Na²⁴). Thirty-four healthy male and female subjects ranging in age from 20 to 34 participated. These volunteer subjects included hospital staff members and medical students.

Thirty-two subjects were intravenously administered 1.0 to 1.5 microcuries of Na²⁴ per kilogram of body weight. Two subjects received the Na²⁴ orally. Four subjects received a second administration 4 to 22 months after the first injection. Blood and urine samples were subsequently obtained and analyzed. In addition to samples from the healthy volunteers, samples of normal bone and brain tissue and cerebrospinal fluid were obtained from patients at the time of regularly scheduled operations.

The results of these studies provided data on the levels of sodium in the subjects. The studies also showed that 82 percent of sodium in the body was exchangeable. This includes 40 percent of the sodium in bone that is considered to be exchangeable. This work was sponsored by the Children=s Research Foundation and the U.S. Atomic Energy Commission.

References

Forbes, G.B., and A. Perley. AEstimation of Total-Body Sodium by Isotopic Dilution. I. Studies on Young Adults.@The Journal of Clinical Investigation. Vol. 30, June 1951, pp. 558B565.  "