List of Experiments

Hanford Sites

HS-1. Ingestion of Iodine-131 in Milk by Hanford Employees

IN 1963, milk from dairy cows fed iodine­131 (I¹³¹) was consumed by eight General Electric/Hanford workers either as a single dose or as several daily doses. During the study, the amount of iodine in the cows=diet was increased from 5 milligrams per day to 2 grams per day. The resulting uptake by the human thyroid was determined in Hanford=s whole-body counter facility. Participants were Hanford scientists who had volunteered to drink the milk and be counted over a period of approximately 1 month. This work was supported by the U.S. Atomic Energy Commission. (Previously described in #41 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Watson, E.C., I.C. Nelson, D.H. Wood, R.O. McClellan, and L.K. Bustad. AEffect of Varying Stable Iodine in Diets of Cows Fed I¹³¹ on Uptake of I¹³¹ in Man Drinking the MilkCAn Abstract.@In Biology of Radioiodine: Proceedings of the Hanford Symposium on the Biology of Radioiodine, Richland, Washington, July 17B19, 1964. Oxford: Pergamon Press, 1964, p. 339.

Handwritten Monthly Report. J.K. Soldat to R.F. Foster. July 1963. Pasco, WA: Washington State University Tri­Cities Campus, PNL, DOE Richland Public Reading Room, I¹³¹, Open Shelving, PNL­936 9­DEL.  "

HS-2. Intentional Release of Iodine-131 at Hanford in 1963

IN JULY 1963, the Hanford Laboratory conducted a study that involved the release of 120 microcuries of iodine­131 (I¹³¹) into the environment. These releases were designed to characterize the dispersion of radiation. The purpose of the experiment was to enable scientists to determine the fraction inhaled by men, the amount taken up by the thyroid, and the retention half-time of radioiodine in human thyroid.

Two volunteer subjects (Hanford employees), were stationed in the expected path of the radiation cloud. These subjects intentionally inhaled I¹³¹ from the release and were subsequently measured for thyroidal uptake of I¹³¹. These experiments were performed under contract with the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995, and since revised)

References

Gamertsfelder, C.C. APlans and Hazard Analysis for the First Hanford I¹³¹ Field Release Test.@Richland, WA: Hanford Atomic Products Operation, Physics and Instruments Laboratory, HW­78312, July 19, 1963. Pasco, WA: Washington State University Tri­Cities Campus, PNL, DOE Richland Public Reading Room, I¹³¹, Open Shelving.

Handwritten Monthly Report. J.K. Soldat to R.F. Foster. July 1963. Pasco, WA: Washington State University Tri­Cities Campus, PNL, DOE Richland Public Reading Room, I¹³¹, Open Shelving, PNL­9369­DEL.

Monthly Report. Senior Engineer to R.F. Foster. August 23, 1963. Pasco, WA: Washington State University Tri­Cities Campus, PNL, DOE Richland Public Reading Room, I¹³¹, Open Shelving, PNL­9370.  "

 ‡  ‡  ‡

HS-3. Absorption of Tritium Oxide Through the Skin

IN 1951, scientists in the Biology Section, Radiological Sciences Department, General Electric Hanford Company examined the percutaneous (through the skin) absorption of tritium (H³) oxide-labeled water vapor in animals and humans. A total of 14 subjects participated in the study.

Twelve subjects were exposed over about 10 square centimeters on the forearm, and two were exposed on the abdomen. One of the arm-exposed subjects also received atmospheric whole-body exposure while breathing H³-labeled air through a respirator. Urine samples were collected from all 14 subjects over a 48-hour period.

The study results indicated that absorption of H³ through the skin and lungs from an H³-contaminated atmosphere contributed similarly to the total-body burden as exposure by H³-water vapor. As a result of this finding, the researchers recommended a 50 percent reduction in the permissible maximum level for atmospheric tritium oxide. This study was funded by the U.S. Atomic Energy Commission. (This experiment was referenced in the Markey report.)

References

DeLong, C.W., R.C. Thompson, and H.A. Kornberg. APercutaneous Absorption of Tritium Oxide.@American Journal of Roentgenology, Radium Therapy and Nuclear Medicine. Vol. 71, No. 6, June 1954, pp. 1,038B1,045.  "

HS-4. Calibration Studies Using Zinc-65

IN 1959, researchers at the General Electric Hanford Company, Atomic Products Operation conducted studies on the retention and distribution of zinc-65 (Zn⁶⁵) in the human body to establish calibration values for bioassay and in vivo counting.

In September 1959, one subject (a Hanford worker) was orally administered an unstated amount of Zn⁶⁵ and the amount remaining in the body was measured by whole-body counting. The uptake of ingested Zn⁶⁵ was found to be 35 percent or about twice the amount expected from results of animal studies. Over time, different values for different individuals suggested that different distribution patterns should be considered.

In March 1960, a study involving one subject showed that Zn⁶⁵ deposited initially in the liver and later in the head and legs. The General Electric Hanford Company was operated at Richland, Washington, for the U.S. Atomic Energy Commission.

References

Bioassay Laboratory Monthly Report, SeptemberB1959.Richland, WA: General Electric Hanford Atomic Products Operation. October 1, 1959.

Radiation Protection Operation Report for the Month of March, 1960. Richland, WA: General Electric Hanford Atomic Products Operation. April 11, 1960.  "

HS-5. Study of Metabolism of Strontium Using Strontium-85 as a Tracer

A STUDY WAS CONDUCTED in 1963 by scientists of the General Electric Hanford Laboratories to (1) determine whether ingested strontium is excreted in human body hair in measurable amounts, (2) determine whether analysis of hair samples was an accurate indicator of strontium uptake in man, and (3) investigate the biological retention of ingested strontium in man.

Two Hanford scientists voluntarily ingested a solution containing a few microcuries of strontium-85 (Sr⁸⁵). The exact amounts administered are not known. Hair clippings and facial shavings were then obtained from the subjects and analyzed for Sr⁸⁵ content.

The results of this study showed that Sr⁸⁵ could not be measured in small samples of body hair. This study was discontinued and the results were never published. The Hanford Laboratories were operated by the General Electric Hanford Company for the U.S. Atomic Energy Commission.

References

Letter. T. Beasley to D.R. Fisher. May 29, 1995.

Letter. B.I. Griffin to D.R. Fisher. May 2, 1995.

Memorandum. D.R. Fisher to file. April 27, 1995.   "

HS-6. Whole-Body Counting Studies of the Measurement of Phosphorus-32

DURING 1963 TO1964, a researcher at the General Electric Hanford Company developed techniques for the whole-body measurement of phosphorus-32 (P³²). The purpose of this study was to develop a more sensitive method for measuring the level of beta-emitting radioisotopes in the body.

Three patients at the University of Oregon Medical school who had received P³² therapy for blood diseases participated as subjects. Two other volunteer subjects at the Seattle Swedish Hospital were administered P³² by injection for calibration study purposes only. Each of the subjects was counted for P³² in the Hanford whole-body counter.

These studies provided P³² calibrations for measurement equipment that later was used in studies of P³² in people who consumed fish from the Columbia River. This work was supported by the U.S. Atomic Energy Commission.

References

Palmer, H.E. ADetermination of P³² In Vivo.@Health Physics. Vol. 12, 1966, pp. 605B608.  "

HS-7. Distribution and Excretion of Technetium-95 and Technetium-96 in Humans

IN APPROXIMATELY 1965, scientists at the Battelle Memorial Institute=s Pacific Northwest Laboratory collected data to establish exposure limits for personnel engaged in the handling of technetium isotopes and for workers in areas where inadvertent exposure might occur.

Eight normal volunteers, between the ages of 23 and 40 years, received 20 microcuries of technetium-95 (Tc⁹⁵) and 60 microcuries of Tc⁹⁶ as pertechnetate. Administrations were by intravenous injection to four subjects, and orally to the other four. Samples of blood, urine, sweat, tears, and intestinal mucosae (biopsies of stomach, duodenal, and rectal mucosae were obtained from three individuals) were collected for the first week; total urine and feces were collected for an additional 8 to 10 days.

The study results indicated that there was no detectable difference between the intravenous and oral administrations in relation to the rate and route of excretion, and the amount excreted. Technetium was found to concentrate primarily in the stomach and gastrointestinal tract, with little or no concentration in the liver or kidney. Blood and urine analyses together were found to provide the best method for assessing external depositions of technetium as pertechnetate following accidental exposure.

The researchers concluded that the recommendations of the International Commission on Radiological Protection on the maximum permissible body burdens and air and water concentrations of technetium as pertechnetate, needed to be reevaluated. This study was funded by the U.S. Atomic Energy Commission. (This experiment was referenced in the Markey report.)

References

Beasley, T.M., H.E. Palmer, and W.B. Nelp. ADistribution and Excretion of Technetium in Humans.@Health Physics. Vol. 12, 1966, pp. 1,425B1,435.  "

HS-8. Study of Promethium Metabolism and the Effects of DTPA on Promethium Metabolism

IN 1967, SCIENTISTS at Battelle Memorial Institute=s Pacific Northwest Laboratory and the Hanford Environmental Health Foundation, conducted a collaborative study on the effects of DTPA (diethylenetriaminepentaacetic acid, a chelating agent) on the retention of promethium-143 (Pm¹⁴³). The purpose of the study was to develop an excretion model for diagnosis of promethium exposure, to form a basis for radiation exposure, and to determine the radiation dose from accidental exposures.

A total of 14 volunteers participated in the study. Six received approximately 0.1 microcurie of Pm¹⁴³ intravenously; two received 10 microcuries of Pm¹⁴³ orally; the final six received 0.1 microcurie of Pm¹⁴³ intravenously, followed at various intervals by intravenous administration of 1 gram DTPA to study its effectiveness in combining with promethium to enhance its rate of excretion. Whole-body counts and excreta measurements were conducted for up to 1 year following these administrations.

Results indicated that DTPA is effective in significantly reducing the body content of promethium when administered within about 1 hour following its entry into the bloodstream. This study was funded by the U.S. Atomic Energy Commission. (This experiment was referenced in the Markey report.)

References

Palmer. H.E., I.C. Nelson, and G.H. Crook. AThe Uptake, Distribution, and Excretion of Promethium in Humans and the Effect of DTPA on those Parameters.@Health Physics. Vol. 18, 1970, pp. 53B61.  "

HS-9. Whole-Body Counting Studies Using Iron-59

IN THE LATE 1960s, researchers in the Department of Medicine, University of Washington, Seattle and Battelle Memorial Institute=s Pacific Northwest Laboratory conducted studies to demonstrate the utility of the whole-body counter for measuring iron-59 (Fe⁵⁹) in humans and to establish the quantitative validity of measuring Fe⁵⁹ absorption and loss by this technique.

Several healthy subjects were orally administered 1 microcurie of Fe⁵⁹. Whole-body counts were obtained immediately after the administration and at 3 to 7 hours thereafter. Subjects then received 1 microcurie of Fe⁵⁹ by direct intravenous injection. Whole-body counts were repeated and compared for consistency. Negligible differences were found between the measurements of interests obtained following oral administration and those obtained following intravenous injection.

Another study was conducted to assess the differences in counting efficiency for Fe⁵⁹ circulating in the blood, and the Fe⁵⁹ localized in the red bone marrow. The researchers were supported by the U.S. Public Health Service and the U.S. Atomic Energy Commission.

References

Palmer, H.E., J.D. Cook, K.G. Pailthorp, and C.A. Finch. AA Whole-Body Counter for Precision In Vivo Measurement of Radio-Iron.@Physics in Medicine and Biology. Vol. 15, No. 3, 1970, pp. 457B465.

Palmer, H.E., J.D. Cook, K.G. Pailthorp, and C.A. Finch. The Precision In Vivo Measurement of Radioiron by Whole-Body Counting. Seattle, WA: University of Washington, Department of Medicine.  "

HS-10. Alternative Method for Measuring Iron Uptake Using Iron-59

A STUDY WAS CONDUCTED in 1969 at the Department of Medicine, University of Washington, Seattle in collaboration with Battelle Memorial Institute=s Pacific Northwest Laboratory on three normal subjects between the ages of 25 and 40 years.

One microcurie of iron-59 (Fe⁵⁹) as ferrous sulphate in water was administered orally to each of the subjects. Whole-body counts were obtained immediately following the oral ingestion, and again 3 and 7 hours later. The latter count was immediately followed by an injection of Fe⁵⁹ in the form of sodium citrate bound with fresh plasma. The experiment was conducted to evaluate a new (about 1970) technique for whole-body counting, namely the use of longitudinal scan geometry. This technique was tested using different biological distributions of Fe⁵⁹ in the body, including point sources, moving sources, and metabolical sources.

The study demonstrated that the longitudinal scan geometry was suitable for measuring radioactivity in humans. The research was supported by grants from the U.S. Public Health Service and the U.S. Atomic Energy Commission.

References

Cook, J.D., H.E. Palmer, K.G. Pailthorp, and C.A. Finch. AThe Measuring of Iron Absorption by Whole-Body Counting.@Physics in Medicine and Biology. Vol. 15, No. 3, 1970, pp. 467B473.

Letter. C.A. Finch to S. Marks. July 17, 1984. Pacific Northwest Laboratory General Human Subjects, Box Alan Rither, PNL-9055-DEL.  "

Idaho Sites

IS-1 Administration of Radioactive Material to Volunteers to Test or Calibrate Analytical Equipment

FROM 1965 TO 1972, as many as 18 employees at the U.S. Atomic Energy Commission=s Health Services Laboratory at the National Reactor Testing Station in Idaho voluntarily swallowed radioactive material or inhaled radioactive noble gases, prior to being placed in whole-body counters. The following radionuclides were used in the experiments: argon-41, potassium­42, manganese­54, cobalt­60, zinc-65, krypton-85m, zirconium-95/niobium-95, ruthenium-106, silver-110m, iodine­131, cesium­132, xenon-133, cesium­137, and cerium-144.

In most of the ingestion cases, the radioactive material was encapsulated in plastic so that no radioactive material was absorbed into body tissues. These measurements were performed to develop and evaluate new whole-body counting equipment and to calibrate that equipment. The whole-body counting equipment was used to measure the amount of radioactivity inside the body of occupational radiation workers exposed to radioactive material. Policies for conducting these experiments limited radiation doses to volunteers to levels below the occupational radiation­protection guidelines in effect at the time. (This experiment was referenced in the Markey report and included in The DOE Roadmap of February 1995.)

References

Anderson, J.I., and D.G. Olson. AA Rotational Technique for Assessing Quantity and Distribution of Body Radioactivity.@Health Physics. Vol. 13, 1967, p. 719.

Anderson, J.I., and D.G. Olson. AComputerized Helical Scanning to Determine the Location of Specific Nuclides in the Human Body.@Health Physics. Vol. 23, 1972, p. 325.

Howard, L.E., J.H. Spikard, and M. Wilhelmsen. AA Human Radioactivity Counter and Medical Van.@Health Physics. Vol. 21, 1971, p. 417.

Olson, D.G. AA Direct Calibration Using Gamma Spectrometry for Measuring Radioactivity in Humans.@Health Physics. Vol. 14, 1968, p. 438.

Sill, C.W. Some Guidelines for Studies Involving Internal Administration of Radioactive Materials to Human Volunteers. Idaho Falls, ID: Idaho Operations Office, U.S. Atomic Energy Commission, IDO­12058, October 1966.  "

IS-2. Controlled Environmental Radioiodine Tests (CERT)

U.S. ATOMIC ENERGY COMMISSION scientists and other professionals at the National Reactor Testing Station in Idaho conducted the Controlled Environmental Radioiodine Tests (CERT) to study the transport of radioiodine through the air­vegetation­cow­milk­human food chain from 1963 through 1968. Five of the 24 CERT tests involved exposure of volunteers to iodine­131 (I¹³¹) to study the transport of radioiodine to and through the human body.

In the first test, CERT No. 1, seven individuals consumed milk from a cow that had grazed in a pasture where the radioiodine was deposited, and their uptake of radioiodine was determined by thyroid gland monitoring. The average thyroid dose was 0.39 rad; the maximum thyroid dose was 0.63 rad.

In CERT Nos. 2, 7, and 10, three individuals, seven individuals, and one individual, respectively, were reportedly exposed during radioiodine releases over the pasture to determine their intake of I¹³¹ by inhalation.

The number of individuals involved in a similar inhalation experiment during CERT No. 11 was not listed in published reports; however, whole-body counting logs indicate that 10 individuals were apparently involved.

Thyroid doses from inhalation during CERT No. 2 were no greater than 0.015 rad, and the reported thyroid activity observed during CERT No. 7 was about the same as that in CERT No. 2. Thyroid doses to volunteers were not reported for CERT Nos. 10 and 11. The volunteers were employees of the U.S. Atomic Energy Commission. (This experiment was referenced in the Markey report and included in The DOE Roadmap of February 1995.)

References

Bunch, D.F., Editor. Controlled Environmental Radioiodine Tests Progress Report Number Two. Idaho Falls, ID: Idaho Operations Office, U.S. Atomic Energy Commission, IDO­12053, August 1966.

Bunch, D.F., Editor. Controlled Environmental Radioiodine Tests, Progress Report Number Three. Idaho Falls, ID: Idaho Operations Office, U.S. Atomic Energy Commission, IDO­12063, January 1968.

Hawley, Jr. C.A., C.W. Sill, G.L. Voelz, and N.F. Islitzer. Controlled Environmental Radioiodine Tests at the National Reactor Testing Station. Idaho Falls, ID: Idaho Operations Office, U.S. Atomic Energy Commission, IDO­12035, June 1964.

Hawley, Jr., C.A., Editor. Controlled Environmental Radioiodine Tests at the National Reactor Testing Station 1965 Progress Report. Idaho Falls, ID: Idaho Operations Office, U.S. Atomic Energy Commission, IDO­12047, February 1966.  "

Lawrence Berkeley Laboratory

rkeley Laboratory
LBL-1. Treatment of Leukemia with Phosphorus-32

BETWEEN 1936 AND 1947, patients with various types of leukemia were treated with phosphorus­32 (P³²) with and without supplemental x­ray treatments. Approximately 129 patients with chronic myelogenous leukemia and 100 patients with chronic lymphatic leukemia were treated at the Radiation Laboratory and the Donner Laboratory of the University of California in Berkeley and San Francisco. Previously it had been demonstrated that radiophosphorus concentrated in the bone marrow and soft tissue of leukemic mice. Therefore, it was expected that P³² would provide a highly localized radiation source for human leukemic patients.

Patients were administered 1 to 2 millicuries of P³² per week for 4 to 8 weeks, although higher doses were also included. Approximately half of the patients studied had previously received x­ray treatment.

It was found that P³² treatment increased the quality of life for chronic myelogenous leukemic patients, but did not prolong the duration of life. In the case of chronic lymphatic leukemia patients, the quality of life was improved and the duration was prolonged. Based on these findings, an unspecified number of chronic lymphatic patients were treated with P³² through 1960. This research was partly supported by grants from the International Cancer Research Foundation. (Included in The DOE Roadmap of February 1995)

References

Lawrence, J.H., R.L. Dobson, B.V.A. Low­Beer, and B.R. Brown. AChronic Myelogenous Leukemia.@Journal of the American Medical Association. Vol. 136, 1948, pp. 672B677.

Lawrence, J.H., B.V.A. Low­Beer, and J.W.J. Carpender. AChronic Lymphatic Leukemia.@Journal of the American Medical Association. Vol. 140, 1949, pp. 585B588. "

LBL-2. Metabolic Studies of Bone Tumors Using Strontium-89

AN EXPERIMENT WAS conducted in 1942 at the Radiation Laboratory of the University of California, Berkeley on the uptake of radiostrontium by bone tumors. Strontium­89 (Sr⁸⁹) was administered to six subjects prior to biopsy or amputation. Tissue samples were collected and analyzed to determine the Sr⁸⁹ uptake.

The subjects consisted of five males and one female, ranging in age from 9 to 54 years. Five of the subjects received intravenous injection solutions which ranged from 326 to 1,462 microcuries. The sixth subject was given 1,183 microcuries of Sr⁸⁹ orally.

This experiment showed that Sr⁸⁹ had therapeutic value in treating certain types of bone cancers. Some of these cancer patients also received therapeutic amounts of Sr⁸⁹ (a few millicuries), but details are not available. This research was supported by the Rockefeller Foundation and the Columbia Fund for Medical Physics. (Included in The DOE Roadmap of February 1995)

References

Treadwell, A. de G., B.V.A. Low­Beer, H L. Friedell, and J.H. Lawrence. AMetabolic Studies on Neoplasm of Bone with the Aid of Radioactive Strontium.@American Journal of the Medical Sciences. Vol. 204, 1942, pp. 521B523.  "

LBL-3. Inhalation Studies Using Carbon-11

FROM 1944 TO 1945, the Aero Medical Laboratory, University of California, Berkeley and the Department of Physiology, Columbia University conducted a collaborative study using carbon-11 (C¹¹). The radioactive carbon was used as a tracer to determine whether carbon monoxide (CO) oxidizes to carbon dioxide (CO₂) in the human body.

The subjects consisted of four men, including three of the researchers conducting the experiment. The four men inhaled a relatively large amount of CO labeled with C¹¹, after which they breathed oxygen. During this time, their expired CO₂ was collected and measured for C¹¹, the presence of which would prove that the human body could convert CO to CO₂. Geiger counters were placed over various parts of the body (thigh, chest, spleen, and liver) to measure the uptake and elimination of CO₂. The CO oxidized to CO₂ amounted to less than 0.1 percent of the CO lost from the blood. This work was supported by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

Lawrence, J.H. Positron Emitting Isotopes: Investigative and Diagnostic Studies. Berkeley, CA: Lawrence Berkeley Laboratory, John Hundale Lawrence Files, pp. 247B262. Accession 434­92­0066, File Code 19­14­6, Carton 15, Folder APositron Emitting Isotopes.A

Tobias C.A., J.H. Lawrence, F.J.W. Roughton, W.S. Root, and M.I. Gregersen. AThe Elimination of Carbon Monoxide from the Human Body with Reference to the Possible Conversion of CO to CO₂.@American Journal of Physiology. Vol. 145, No. 2, December 1945, pp. 253B263.  "

LBL-4. Inhalation of Zirconium-89 on Smoke Particles

INHALATION STUDIES were conducted at Lawrence Berkeley Laboratory in approximately 1945 using an active smoke containing zirconium­89 (Zr⁸⁹). One member of the research team was the only subject. The purpose of this experiment was to determine the degree of retention by the lungs of very finely divided active smoke suspended in air. The results showed that almost 100 percent of the inhaled activity (about 0.5 microcurie of Zr⁸⁹) was retained within the lungs and upper respiratory tract. This work was supported by the U.S. Atomic Energy Commission. (Previously described in #30 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Scott, K.G., D. Axelrod, J. Crowley, and J.G. Hamilton. ADeposition and Fate of Plutonium, Uranium and Their Fission Products Inhaled as Aerosols by Rats and Man.@Archives of Pathology. Vol. 48, No. 1, JulyBDecember 1949, pp. 31B54.  "

LBL-5. Radioactive Phosphorus as a Possible Diagnostic Procedure for Breast Tumors

IN 1946 , the University of California Hospital, San Francisco, employed phosphorus­32 (P³²) in tracer studies to develop a new diagnostic procedure for distinguishing between malignant and benign breast tumors. Twenty­five female patients with breast tumors were included in the study. All patients had been scheduled for surgery.

Each patient was intravenously administered 300 to 500 microcuries of P³² as sodium phosphate 24 or 48 hours prior to surgery. Surface measurements were made over the tumor and over a control area on the opposite normal breast, 2, 4, 6, and 20 hours after the injection of P³². An increase in counts was found over the surface of malignant tumors, whereas counts were not elevated over benign tumors. The malignancy of the tumor was determined after surgical removal.

Results indicated that P³² might be used as a diagnostic procedure for breast cancer, except for very slow­growing or deep­seated cancers. (Included in The DOE Roadmap of February 1995)

References

Low­Beer, B.V.A., H.G. Bell, H.J. McCorkle, R.S. Stone, H.L. Steinbach, and W.B. Hill. AMeasurement of Radioactive Phosphorus in Breast Tumors in Situ: A Possible Diagnostic Procedure.@Radiology. Vol. 47, pp. 429B496.  "

LBL-6. Comparison of the Uptake of Zirconium-95 in Tumor and Normal Tissue

IN 1946, at the University of California, San Francisco and the Crocker Radiation Laboratory, University of California, Berkeley research was carried out to study the uptake and deposition of zirconium. The subject, a 55­year­old female patient with a reticulo endothelial tumor that had arisen in the spleen and then metastasized to the liver and left leg, was given a test dose of zirconium-95 (Zr⁹⁵).

The subject was administered 1.76 millicuries of Zr⁹⁵ in saline by intravenous injection 24 hours prior to a scheduled midthigh amputation of the left leg. Samples of the tumor, as well as normal tissue, were later obtained from the limb for Zr⁹⁵ assay.

The tumor was found to have greater uptake of Zr⁹⁵ than the normal tissues of the body. External counting 2 hours after the Zr⁹⁵ injection showed that the liver contained about 90 percent of the total measurable deposition and the tumor had about 10 percent of the total deposition. This study was supported by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

Low­Beer, B.V.A., K.G. Scott, J.G. Hamilton, and R.S. Stone. AComparative Deposition of Zr⁹⁵ in a Reticulo Endothelial Tumor to Normal Tissues in a Human Patient.@Berkeley, CA: University of California Radiation Laboratory, UCRL­68.   "

LBL-7. Autoradiographic Studies of the Distribution of Radiolabeled Lewisite and Mustard Gas on Skin

THIS EXPERIMENT was conducted in 1947 at the Crocker Radiation Laboratory, University of California, Berkeley and the University of California Medical School in San Francisco. The experiment sought to determine the distribution of mustard and lewisite in skin and eye tissues. These two chemical­warfare gases were labeled with radioactive sulfur (S³⁵) and radioactive arsenic (As⁷⁴). Small areas of the skin of four normal subjects were exposed to the two labeled gases.

Two experiments were performed with mustard gas labeled with S³⁵. The first involved a 10­minute exposure to 475 micrograms of labeled chemical; the second, a 15­minute exposure to 475 micrograms. In both cases, the exposed area was 0.43 square centimeter and biopsy specimens of these areas were taken 24 hours after exposure.

Two experiments were also performed on lewisite labeled with 10 micrograms of As⁷⁴; the first involved a 10­minute exposure to 475 micrograms of lewisite; the second, a 15­minute exposure to 475 micrograms. The new technique of autoradiography was used to determine the skin layer at which the fixation took place on the biopsied human skin samples. Lewisite was found to fix primarily in the epidermis, and mustard gas fixed in both the epidermis and dermis. (Included in The DOE Roadmap of February 1995)

References

Axelrod, D.J., and J.G. Hamilton. ARadio­Autograph Studies of the Distribution of Lewisite and Mustard Gas in Skin and Eye Tissues.@American Journal of Pathology. Vol. 23, 1947, pp. 389B411.  "

LBL-8. Injection of Americium-241

ON JUNE 10, 1947, at the University of California, San Francisco a 16­year­old Chinese male patient at the Chinese Hospital in San Francisco, identified as Cal­A, with osteogenic sarcoma of the left femur and general metastases, received an intramuscular injection of americium­241 (Am²⁴¹). The estimated activity administered was about 0.2 microcurie. The same day, two rats were given intramuscular injections of 1 milliliter of solution made from the same specifications as the Cal­A injection.

Readings of the subject=s urine and feces were collected through at least June 24, 1947. On June 12, 1947, the subject=s leg was amputated at the left midthigh. Samples of the amputation tissue were dissected the next day. The samples were measured for isotope uptake, as the tumor was expected to have higher uptake than normal body tissues. Studies were made of the tumor; the bone tissue in which the tumor was found; the surrounding tissues, both bone and connective; and the muscles. Measurements from the amputated tissues were compared with the rat data; the patient was discharged on July 27, 1947.

Rat data showed considerable uptake by the liver; human data appeared to show 13 to 20 percent uptake by the bone. The patient died of preexisting ailments on June 15, 1948.

The experiment appears to have been done as a comparison to previous human studies involving plutonium, as data sheets for Cal­A show standards for measurements set against Cal­1 (a human injected with plutonium­238). (Included in The DOE Roadmap of February 1995)

References

Lawrence Berkeley Laboratory, Joseph G. Hamilton Records, Archives and Records Office, Folder Am H (95H).  "

LBL-9. Uptake of Iodine-131 in Thyroids of Psychiatric Patients

FROM JULY 1949 TO APRIL 1950 a cooperative research project was conducted by the Departments of Psychiatry, Radiology, and Medicine at the University of California Medical School and the Langley Porter Clinic in San Francisco. The objective of this project was to determine whether thyroid function was normal or abnormal in persons with mental illness. Sixty­five subjects were selected from the regular in­patient group at the Langley Porter Clinic.

Among the subjects were patients with schizophrenia, manic­depression, mixed psychoneurosis, and anorexia nervosa. A control group was selected of volunteers from the clinic=s, clerical, and medical staff.

Subjects were injected with 150 microcuries of iodine­131 (I¹³¹); subsequently, the concentration of I¹³¹ in the thyroid was then measured six times over a 72-hour period. The test and control groups underwent medical and psychiatric evaluations, including serum­bound iodine, basal metabolism, plasma cholesterol, and electroencephalogram.

No abnormal thyroid function was found in the group with mental illness and no significant differences were detected between the patients and the controls in this study. This study was partly funded by the U.S. Atomic Energy Commission. (Previously described in #2 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Bowman, K.M., E.R. Miller, M.E. Dailey, A. Simon, B. Frankel, and G.W. Lowe. AThyroid Function in Mental Disease Measured with Radioactive Iodine, I¹³¹.@The American Journal of Psychiatry. Vol. 106, No. 7, February 1950.

Stone, R.S. Biological Effects of Radiations from External and Internal Sources, Progress Report July 1, 1949 to April 15, 1950. San Francisco: University of California Radiation Laboratory, April 1950. U.S. Department of Energy Archives, Record Group 326, U.S. Atomic Energy Commission, Box 3358, Folder 22.  "

LBL-10. Sodium-24 Uptake Studies on Patients with Rheumatoid Arthritis

DURING THE MID-1940s through the early 1950s, Lawrence Berkeley Laboratory conducted studies on the uptake of sodium­24 (Na²⁴) to evaluate vascular abnormalities in persons with rheumatoid arthritis.

Sodium­24 was administered by intravenous injection, usually in 50­microcurie amounts. Systemic transport of Na²⁴ was followed, using two gamma counters: one in the subject=s hand, the other placed under a knee.

The results showed an impeded blood flow in diseased areas of the body. Uptake of Na²⁴ in the knee joint was also studied after three patients drank a solution of sodium chloride labeled with Na²⁴ in water. (Included in The DOE Roadmap of February 1995)

References

Tobias, C. Sodium Uptake Studies. Berkeley, CA: Lawrence Berkeley Laboratory, Cornelius A. Tobias Papers, Accession 434­89­100, File Code 10­08­063, Carton 25/38, Folder ASodium Uptake Studies.@ "

LBL-11. Blood Volume Studies with Iron-59, Phosphorus-32, and Chromium-51 Involving Inmates at San Quentin Prison

FROM 1949 TO THE LATE 1950s, the University of California conducted studies involving radioactive isotopes using inmates at San Quentin Prison as volunteer subjects. Studies included the following: (a) 1949 to 1951: studies on red blood-cell productionCBlood was drawn from participants, labeled with iron­59 (Fe⁵⁹), and reinjected into the respective subjects. Four samples were drawn at specific intervals over the next 2 hours. The procedure was repeated for 4 successive days, during which Fe⁵⁹­labeled red blood cells were counted. (b) 1950: studies on blood volumeCAt least 13 participants had blood drawn, labeled with phosphorus­32 (P³²), and reinjected. Blood volume in the subjects was subsequently measured. (c) late 1950s: Studies on red cell volumeCChromium­51 (Cr⁵¹) was used as a label to measure red blood-cell volume in 201 healthy participants. (Included in The DOE Roadmap of February 1995)

References

Wennesland, R., E. Brown, J. Hopper, Jr., J.L. Hodges, Jr., O.E. Guttentag, K.G. Scott, I.N. Tucker, and B. Bradley. ARed Cell, Plasma, and Blood Volume in Healthy Men Measured by Radiochromium (Cr⁵¹) Cell Tagging and Hemocrit.@The Journal of Clinical Investigation. Vol. 38, No. 7, July 1959, pp. 1,065B1,077.

Donner Laboratory Clinical Books, 1946B1977. Patient Sheets from February to March 1950, noted ASan Quentin@after patient=s name. Lawrence Berkeley Laboratory. Donner Laboratory Clinical Logs and Notebooks, Accession 439­89­0151, File Code 8­2­2, Carton 7/10, Binder 2.

Letter. J.H. Lawrence to J.H. Corley. August 17, 1949. Lawrence Berkeley Laboratory, Administrative Files of Administrative Assistants to the Directors of the Biology and Medicine Division and Donner Laboratory, Accession 434­90-0209, File Code 16­5­22, Carton 2, Folder AHistorical Donner Laboratory.@  "

LBL-12. Blood and Tissue Studies with Iron­59

THIS RESEARCH was conducted at the Donner Laboratory, University of California, Berkeley in the early 1950s. The purpose of this study was to investigate the rates and pathways of iron transport in the human body, including the differences in iron turnover rates between normal individuals and patients with anemia. The subjects consisted of 22 individuals with anemia and other diseases and 16 normal individuals.

Between 5 and 30 microcuries of radioactive iron-59 (Fe⁵⁹) globulin were injected intravenously to label the circulating plasma iron globulin. External radiation measurements were made on the liver, spleen, and bone marrow using a gamma­fluorescence detector. In addition, plasma and whole-blood samples were analyzed for Fe⁵⁹ content.

The results showed that iron turnover rates varied, the exact rate depending on the disease state of the patient. This research was partly funded by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

Elmlinger P.J., R.L. Huff, C.A. Tobias, and J.H. Lawrence. AIron Turnover Abnormalities in Patients Having Anemia: Serial Blood and In Vivo Tissue Studies with Fe⁵⁹.@Acta Haematologica. Vol. 9, No. 2, February 1953, pp. 73B96.

Huff, R.L., C.A. Tobias, and J.H. Lawrence. AA Test for Red Cell Production.@Acta Haematologica. Vol. 7, No. 3, March 1952, pp. 129B143.  "

LBL-13.

(Duplicate of LBL-10 in The DOE Roadmap)

LBL-14. Studies on the Rate of Uptake of Iodine-131 in the Thyroid

IN THE EARLY 1950s, studies were conducted at the University of California, San Francisco on various aspects of thyroid function in patients with normal and abnormal thyroid glands. The 427 study participants included patients with normal and abnormal thyroids as well as goiters or uncertain thyroid functions.

After the subjects drank a solution containing approximately 100 microcuries of iodine­131 (I¹³¹), an external gamma counter was placed over the thyroid to measure the uptake of radioiodine. A good correlation was found between high rates of uptake and hyperthyroidism, and between lower rates and absence of hyperthyroidism.

Further research was also conducted to study aspects of the physiology of the thyroid and other endocrine glands. Studies were conducted on obese patients, and on adult and child hyperthyroid patients requiring thyroid stimulating hormone. This research was funded by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

Miller, E.R., M.E. Dailey, A.V. Holmes, G.L. Alexander, and G.E. Sheline. AStudies with Radioiodine: I. Function and Rate of I¹³¹ Uptake of Thyroid.@Radiology. Vol. 57, No.1, July 1951, pp. 37B47.

Annual Report of Cancer Activities of the Radiological Laboratory. San Francisco: University of California School of Medicine, 1953, pp. 1B9. Special Collections, The Library, University of California, San Francisco.  "

LBL-15. Measures of Body Fat and Related Factors in Normal Adults Using Potassium-40, Cesium-137, and Tritium

DURING 1950 TO 1960,  the Donner Laboratory at the University of California, Berkeley, in collaboration with the California State Department of Public Health and the Bureau of Public Health Nutrition, conducted a series of experiments using natural potassium­40 (K⁴⁰) and cesium­137 (Cs¹³⁷) to measure body composition. The experiments were designed to accurately determine the human body=s total water content, body fat, protein content, and bone mineral content. In all, 2,301 healthy volunteers were used for these experiments.

The laboratory analyses included measurements of total-body water after an oral tracer dose of tritium, analysis of specific gravity by the helium dilution technique, and whole-body counting of K⁴⁰. This study was partly supported by a grant from the National Institutes of Health. (Included in The DOE Roadmap of February 1995)

References

Steinkamp, R.C., N.L. Cohen, W.R. Gaffey, T. McKey, G. Bron, W.E. Siri, T.W. Sargent, and E. Isaacs. AMeasures of Body Fat and Related Factors in Normal Adults­II.@Journal of Chronic Diseases. Vol. 18, 1965, pp. 1,279B1,289. "

LBL-16. Study of Ascitic Fluid Using Tritium-Labeled Water and Phosphorus-32

DURING 1951 AND 1952, the University of California Donner Laboratory and the Highland Alameda County Hospital, Oakland conducted experiments to determine the total amount of ascitic fluids in humans. Tritium (H³) was used to trace the flow of water into, and out from, the peritoneal cavity.

Six patients with ascites (a condition characterized by fluid buildup in the peritoneal cavity) were injected with 2 microcuries of tritium­labeled water, either intravenously or intraperitoneally. Over the following 7 to 24 hours, samples of blood and ascitic fluid were taken. Blood samples were labeled with phosphorus­32 (P³²) and 1 milliliter of the labeled blood was injected into the peritoneal cavity.

This study showed that the water content of ascitic fluid entered and left the peritoneal cavity at a very rapid rate. It also showed that the peritoneal surfaces of both normal and diseased subjects reabsorbed large volumes of fluid. This work was supported by the Life Insurance Medical Research Fund and the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

Prentice, T.C., W. Siri, and E.E. Jones. AQuantitative Studies of Ascitic Fluid Circulation with Tritium­Labeled Water.@American Journal of Medicine. Vol. 13, No. 6, December 1952, pp. 668B673.  "

LBL-17. A Physiological Study in the Peruvian Andes Using Iron-59

THE DONNER LABORATORY of Medical Physics, University of California, Berkeley used iron­59 (Fe⁵⁹) in high­altitude studies similar to the previously conducted studies using tritium (H³). The purpose of these experiments was to investigate the physiology of reduced barometric pressure, particularly as seen in high­altitude flights, and the physiology and treatment of various hematopoietic (blood­forming) disorders, especially polycythemia rubra vera, leukemia, and aplastic anemia.

In these studies, reported in 1952, healthy subjects (medical students from the University of San Marcos, Lima, Peru) and native Peruvians in the Andes mountains were studied. Four Andean natives suffering from pulmonary silicosis (as well as high­altitude polycythemia rubra vera) were also studied.

A few micrograms of Fe⁵⁹ were incubated for 20 minutes with 10 to 20 milliliters of the subject=s plasma and then injected into the subjects. After injection, Fe⁵⁹ analysis was made on plasma samples taken at hourly intervals for 4 to 5 hours. Acclimatization to high altitude was found to be related to changes in blood volume, plasma volume, and red blood­cell mass. Postexposure plasma­iron turnover rates and red cell renewal rates increased to roughly twice their normal values in less than 12 hours at high altitude. This study was supported by the U.S. Navy, the U.S. Air Force, and the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

Lawrence, J.H., R.L. Huff, W. Siri, L.R. Wasserman, and T.G. Hennessy. AA Physiological Study in the Peruvian Andes.@Acta Medica Scandinavica. Vol. 142, No. 2, 1952, pp.117B133.  "

LBL-18. Studies on the Metabolism of Glycine Labeled with Carbon-14

DURING THE EARLY 1950s, researchers at the University of California Donner Laboratory conducted studies on human carbon metabolism using carbon-14 (C¹⁴). Twelve patients participated in two studies that examined the distribution, retention, and excretion of C¹⁴.

In one study, four patients, ranging in age from 29 to 52 years, were intravenously administered 100 microcuries of C¹⁴-labeled glycine (an essential nutrient and a dietary supplement). Activity as C¹⁴O₂ was measured in their exhaled breath and in tissue samples subsequently collected at autopsy. Five additional patients received similar injections and C¹⁴ activity was measured in their urine samples.

In a second study, which examined the retention of C¹⁴ in hemoglobin precursors, three patients were administered 100 microcuries of C¹⁴-labeled glycine and activity was measured in hippuric acid isolated from their urine samples.

The results of these studies showed that exhalation of C¹⁴O₂ was the primary route of C¹⁴ excretion, with a small percentage being excreted through urine. The studies also showed a small concentration in tissue and a biological retention half-time for C¹⁴ of 50 days. Finally, the studies showed that retention in the blood was due to absorption by newly formed cells, not long-lived existing cells. This work was supported by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995, and since revised)

References

Berlin, N.I., B.M. Tolbert, and J.H. Lawrence. AStudies in Glycine-2-C¹⁴ Metabolism in Man: I. The Pulmonary Excretion of C¹⁴O₂.@Journal of Clinical Investigation. Vol. 30, 1951, pp. 73B77.

Berlin, N.I., B.M. Tolbert, and J.H. Lawrence. AStudies in Glycine-2-C¹⁴ Metabolism in Man: II. Tissue Distribution.@Journal of Clinical Investigation. Vol. 31, 1952, pp. 335B337.

Berlin, N.I., B.M. Tolbert, and H.C. Lee. AStudies in Glycine-2-C¹⁴ Metabolism in Man: III. The Urinary Excretion of C¹⁴ and Cumulative Radiation Dosimetry.@Journal of Clinical Investigation. Vol. 32, 1953, pp. 1B4.

Berlin, N.I., C. Hewitt, and C. Lotz. AHippuric Acid Synthesis in Man After the Administration of ["-¹⁴C] Glycine.@The Biochemical Journal. Vol. 58, 1954, pp. 498B503.  "

LBL-19. Astatine-211 and the Thyroid

THE OBJECTIVE of this experiment was to test the uptake of astatine­211 (At²¹¹) and to evaluate its potential benefits in the treatment of thyroid diseases. Eight subjects were injected with 50 microcuries of the 7­hour half­life alpha emitter At²¹¹. These experiments were conducted at the University of California Hospital during early 1954. (Previously described in #37 on the original list of 48 experiments released by DOE in June 1994 and included in The DOE Roadmap of February 1995)

References

Hamilton, J.G., P.W. Durbin, and M.W. Parrott. AAccumulation of Astatine by Thyroid Gland in Man.@In Proceedings of the Society for Experimental Biology and Medicine. Vol. 86, 1954, pp. 366B369.

Hamilton, J.G., P.W. Durbin, and M.W. Parrott. AComparison of Acute and Chronic Changes Produced in Rats by I¹³¹ and At²¹¹ at Lethal Levels. Preliminary Data on the Uptake of At²¹¹ in Patients with Thyroid Disease.@Chapter 24 in Proceedings of the 2nd Radioisotope Conference in Oxford, England. pp. 219B231. London: Butterworth Scientific Publications, July 1954.  "

LBL-20. Body Water at Sea Level and at High Altitudes by Tritium Analysis

IN 1954, SCIENTISTS from the Donner Laboratory, University of California, Berkeley, and the Instituto de Biologia Andina, Lima, Peru, used tritium (H³) to determine changes in weight and total-body water for subjects living in Lima at high altitudes and at sea level. Two groups of subjects were studied. The first group consisted of 15 young male medical students; the second group consisted of 13 normal male Peruvian Indian mine workers.

The tritium was administered both orally and intravenously. The mean values of body water for the two groups was normal for their age range and occupations. This research was supported by the U.S. Public Health Service, the U.S. Atomic Energy Commission, and the U.S. Air Force. (Included in The DOE Roadmap of February 1995)

References

Siri, W.E., C. Reynafarje, N.I. Berlin, and J.H. Lawrence. ABody Water at Sea Level and at Altitude.@The Journal of Applied Physiology. Vol. 7, No. 3, November 1954, pp. 333B334.  "

LBL-21. High-Energy-Beam Irradiation of Breast Cancer Patients

DURING THE 1950s AND EARLY 1960s, researchers at Donner Laboratory and Lawrence Radiation Laboratory, University of California conducted studies on therapeutic heavy particle beam irradiation. The purpose of these studies was to evaluate the results of pituitary irradiation in the treatment of a variety of hormone-dependent diseases.

An early study involved 26 breast cancer patients ranging in age from 27 to 70 years who received between 14,000 and 30,000 rads of 340-MeV (million electron-volt) radiation to the pituitary gland over periods of 9 to 63 days. Beginning in 1954, 159 breast cancer patients received therapy involving 900-MeV alpha particles produced by an accelerator. All patients were either in a terminal state or a state of rapid disease advancement despite all routinely available treatment. Radiation doses to the pituitary ranged from 14,000 to 17,000 rads delivered over 11 days. During the course of treatment, patients also underwent various diagnostic tests involving the use of internally administered iodine-131, carbon-14, and calcium-47. The results of these studies showed limited supression of tumor growth.

Beginning around 1956, 79 diabetes patients received heavy particle therapy in an attempt to slow degeneration of the retina. Doses ranged from 8,000 to 12,000 rads delivered over 11 days. The results of the study showed that diabetics with advanced complications did not benefit much from this therapy. Also beginning around 1956, 21 patients received therapy for acromegaly (a disease characterized by enlargement of the head, hands, feet, and thorax). Doses ranged from 3,000 to 7,200 rads delivered over 11 days. Follow-up studies showed beneficial changes in patients.

From 1957 to 1961, three female patients with Cushing=s disease received therapy of 5,000 to 10,000 rads delivered over 11 days. All showed some benefit, from minor improvement to general remission. Three patients received up to 10,000 rads over 11 days to treat malignant exophthalmos. One patient showed beneficial results.

In 1958, one breast cancer patient was treated with direct tumor therapy (not pituitary irradiation) of 2,500 rads over 6 days and experienced temporary remission. These studies were supported by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995, and since revised)

References

Lawrence, J.H., C.A. Tobias, J.L. Born, A. Gottschalk, J.A. Linfoot, and R.P. Kling. AAlpha Particle and Proton Beams in Therapy.@Journal of the American Medical Association. Vol. 186, No. 3, October 1963, pp. 236B245.

Tobias, C.A., J.H. Lawrence, J.L. Born, R.K. McCombs, J.E. Roberts, H.O. Anger, B.V.A. Low-Beer, and C.B. Huggins. APituitary Irradiation with High-Energy Proton Beams: A Preliminary Report.@Cancer Research. Vol. 18, No. 2, February 1958, pp. 121B134.  "

LBL-22. Iron-59 Metabolism in Patients with Cancer and Anemic Conditions

STUDIES WERE CONDUCTED in 1959 at the University of California Lawrence Radiation Laboratory on the metabolism of iron in humans using iron­59 (Fe⁵⁹) as a tracer. The aim of these studies was to determine the effects of age, gender, and health status on iron metabolism in humans. Approximately 80 cancer patients and subjects with various anemias, hemochromatosis (a disease characterized by an excessive absorption of iron), and iron deficiencies were used in these studies.

The rate of hemoglobin synthesis, mean red blood­cell life span, and mean time required for hemoglobin formation within the total red cell volume were measured. Gastrointestinal bleeding was correlated with iron and red cell movement in seven subjects. This work was supported by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

Polycove, M., and J.H. Lawrence. AIron Metabolism.@University of California Lawrence Radiation Laboratory Project Description. Berkeley, CA: Lawrence Berkeley Laboratory, June 30, 1959. Cornelius A. Tobias Papers, Accession 434­92­0154, File Code 19­14­43, Carton 21, Folder AProgram Book.@ "

LBL-23. Radionuclide Studies to Determine Bone Marrow Distribution in Humans

IN THE EARLY 1960s, at the Donner Laboratory and the Lawrence Radiation Laboratory, University of California, Berkeley, iron­52 (Fe⁵²), iron­59 (Fe⁵⁹) and technetium­99m (Tc^99m)Bsulfur colloid were administered to study marrow distribution. The marrow, liver, and spleen were then imaged, using conventional scanners or scintillation cameras. Administered activities ranged from 3 to 100 microcuries. Samples of bone marrow, plasma, red cells, and liver were analyzed to determine tissue activity over time. Subjects included hospital patients and normal volunteers, including children. This work was supported in part by the U.S. Atomic Energy Commission and in part by a grant from the National Cancer Institute of the National Institutes of Health. (Included in The DOE Roadmap of February 1995)

References

Lawrence, J.H. Positron Emitting Isotopes: Investigative and Diagnostic Studies. Berkeley, CA: Lawrence Berkeley Laboratory, pp. 247B262. John Hundale Lawrence Files, Accession 434­92­0066, File Code 19­14­6, Carton 15, Folder APositron Emitting Isotopes.@

Van Dyke D.C., H.O. Anger, and Y. Yano. AProgress in Determining Bone Marrow Distribution In Vivo.@Progress in Atomic Medicine. Vol. 2, 1968, pp. 65B84.  "

LBL-24. Iron Kinetics and Hemoglobin Synthesis in Human Subjects with Iron-59BBound Plasma

THIS STUDY WAS conducted in approximately 1959 at the University of California, Berkeley in collaboration with the Veterans Administration in Boston. Its purpose was to develop a suitable mathematical model of hemoglobin synthesis, using sequential measurements of iron­59 present in human plasma, red cells, and peripheral blood. Data were obtained from 13 normal, healthy subjects (1 female and 12 male volunteers) between the ages of 24 and 72 years, and 6 male hospital patients with endogenous hemochromatosis.

Five to 20 milliliters of plasma labeled with 10 to 40 microcuries of iron­59 (Fe⁵⁹) were intravenously injected into the subjects. Plasma and erythrocyte radioactivity were measured with a scintillation counter. This study was supported by the U.S. Atomic Energy Commission with partial support by a grant from the U.S. Public Heath Service. (Included in The DOE Roadmap of February 1995)

References

Pollycove, M., and R. Mortimer. AThe Quantitative Determination of Iron Kinetics and Hemoglobin Synthesis in Human Subjects.@Journal of Clinical Investigation. Vol. 40, 1961, pp. 753B772.   "

LBL-25. Intestinal Iron Absorption Studies Using Iron-52, Iron-55, and Iron-59

IN A STUDY CONDUCTED at the Donner Laboratory, University of California, Berkeley in 1966, radioactive isotopes of iron were used to measure the rate of iron absorption into the plasma and its distribution in the gastrointestinal tract.

Forty microcuries of iron­52 (Fe⁵²) were administered orally to six fasting normal subjects. Just prior to the oral dose, iron turnover studies were performed using 2 microcuries of transferrin­bound iron­59 (Fe⁵⁹) injected intravenously; the subjects were then whole-body counted. For the iron turnover studies, 20 to 30 microcuries of iron­55 (Fe⁵⁵) were injected into the same subjects. Photoscans of the abdomen using the Anger positron camera were taken throughout the study. The maximum rate of intestinal iron absorption was found to occur at the time when iron was in the upper gastrointestinal tract. This work was supported by the U.S. Atomic Energy Commission. (Included in The DOE Roadmap of February 1995)

References

Fawwaz, R.A., H.S. Winchell, M. Pollycove, T. Sargent, H. Anger, and J.H. Lawrence. AIntestinal Iron Absorption Studies Using Iron­52 and Anger Positron Camera.@Journal of Nuclear Medicine. Vol. 7, 1966, pp. 569B576.  "

LBL-26. Chromium-51 Metabolism Studies in Patients with Hemochromatosis

CHROMIUM-51 METABOLISM studies were conducted at Lawrence Berkeley Laboratory on healthy males and on patients with hemochromatosis (a disease characterized by an excessive absorption of iron).

Five normal male subjects were injected with 100 microcuries of chromium-51 (Cr⁵¹) to study the retention of chromium. This study was conducted to show that hemochromatic diabetes was due to the exclusion of chromium from either the carrying agent or from the liver because of saturation by iron.

Eleven subjects were injected with Cr⁵¹­chloride. Among the subjects were patients with varying degrees of hemochromatosis, including two hemochromatotic patients depleted of excess iron and two subjects with excess iron but no clinical disease. All of the subjects were followed by whole-body counting for up to 6 months.

The results showed that the exclusion of chromium occurs principally at binding sites in the liver. Two further studies were conducted on chromium metabolism using plasma analysis, Cr⁵¹ clearance rates, the whole-body scanner, and the whole-body counter. This work was supported by the U.S. Department of Energy. (Included in The DOE Roadmap of February 1995)

References

Lim, T.H., T. Sargent, and N. Kusubov. AKinetics of Trace Element Chromium (III) in the Human Body.@American Journal of Physiology. Vol. 244, Vol. 4, April 1983, pp. R445B454.

Sargent T.W., and H.H. Stauffer. AHuman In Vivo Kinetics of Radionuclide Trace Metals in Health and Disease.@University of California Lawrence Berkeley Laboratory Project Description. Berkeley, CA: Lawrence Berkeley Laboratory, May 1, 1976. Lawrence Berkeley Laboratory, Cornelius A. Tobias Papers, Accession 434­32­0154, File Code 19­14­43, Carton 22, UCLBL Project Descriptions.  "

LBL-27. Calcium-47 Retention Studies in Juvenile Diabetics

THIS RESEARCH was conducted at the Berkeley Donner Laboratory in the early 1970s. This study was undertaken to determine the rate of uptake and retention of calcium­47 (Ca⁴⁷) in juvenile diabetics. The subjects consisted of eight healthy individuals, of various ages and diets, and three juvenile diabetics (ages 23, 26, and 26).

One to 25 microcuries of Ca⁴⁷ was intravenously administered and the retention of Ca⁴⁷ in the whole body was determined by direct in vivo counting.

The whole-body retention of Ca⁴⁷ did not significantly vary over the wide range of calcium and protein intakes and ages of healthy subjects. Diabetics excreted Ca⁴⁷ at a higher rate.

This work showed a decreased rate of bone mineralization in diabetics. The research was supported by the U.S. Energy Research and Development Administration. (Included in The DOE Roadmap of February 1995)

References

Sargent, T., J. Linfoot, and H. Stauffer. ADecreased Whole-Body Retention of Ca⁴⁷ in Juvenile Diabetics.@IRCS Medical Science Journal. Vol. 4, 1976, p. 58.

Sargent T.W., and H.H. Stauffer. AHuman In Vivo Kinetics of Radionuclide Trace Metals in Health and Disease.@University of California Lawrence Berkeley Laboratory Project Description. Berkeley, CA: Lawrence Berkeley Laboratory, May 1, 1976. Lawrence Berkeley Laboratory, Cornelius A. Tobias Papers, Accession 434­32­0154, File Code 19­14­43, Carton 22, UCLBL Project Descriptions.  "

LBL-28. Whole-Body Counting Studies on the Retention of Copper-67 and Phosphorus-32 and Chromium-51

IN THE MID- TO LATE 1970s, the University of California Lawrence Berkeley Laboratory conducted studies on the retention of radionuclides in humans. The subjects were healthy individuals and patients with a variety of diseases.

Four subjects were injected with 100 microcuries of copper­67 (Cu⁶⁷) to determine copper uptake, retention, and excretion rates. Of the four subjects, three were healthy, and one had a copper storage disease. The results showed that there is no abnormality of total-body turnover of copper when iron stores are normal. Results also showed that for the subject with the copper storage disease, the excretion of copper was slower than for normal subjects by a factor of two.

Six subjects with diseases related to bone marrow production were injected with 1 to 5 millicuries of phosphorus­32 (P³²) to determine excretion rates. This was one of the first published studies on human whole-body phosphorus turnover.

Five subjects received injections of 100 microcuries of chromium-51 (Cr⁵¹). The whole-body retention and excretion rates of Cu⁶⁷, P³², and Cr⁵¹ were reported. This work was supported by the U.S. Department of Energy. (Included in The DOE Roadmap of February 1995 and since revised.)

References

Sargent, T.W., and H. Stauffer. AWhole-Body Counting of Retention of Cu⁶⁷, P³², and Cr⁵¹ in Man.@International Journal of Nuclear Medicine and Biology. Vol. 6, 1979, pp. 17B21.  "

LBL-29. Metabolism of Carbon-14 B Labeled Methionine in Schizophrenics

THIS RESEARCH was conducted in the 1980s at the Lawrence Berkeley Laboratory. Researchers suspected that a defect in the methyl­carbon metabolic pathway was a causative factor in schizophrenia. Methionine labeled with carbon­11 (C¹¹) or carbon­14 (C¹⁴) was administered to both schizophrenics and healthy subjects to test this hypothesis. The oxidation of methionine was studied in seven unmedicated schizophrenics, and the effect of high and low methionine in the diet was studied in control subjects. This research was supported by the National Institute of Mental Health, the Donner Laboratory, and the U.S. Department of Energy. (Included in the DOE Roadmap of February 1995)

References

Sargent, T.W. AMetabolism of [C¹⁴­Methyl]-Methionine in Schizophrenia and Affective Disorders.@U.S. Public Health Service, Food and Drug Administration, Radioactive Drug Research Committee, Report on Research Use of Radioactive Drug Study Summary. Berkeley, CA: Lawrence Berkeley Laboratory, Director=s Office, LBL Associated Laboratory, Director for Administration R&D FilesC1981B1987, Accession 434­91­0176, File Code 13­11­14, Carton 58/58, Folder ABiology/Medicine General FY87.@

Sargent, T.W. AMetabolism in Brain Disorders.@U.S. Department of Energy Field Task Proposal/Agreement. Berkeley, CA: Lawrence Berkeley Laboratory, April 1, 1982. Cornelius A. Tobias Papers, Accession 434­92­0154, File Code 19­14­43, Carton 21, Field Task Proposals/Agreements.

Sargent, T.W., N. Kusubov, S. Taylor, and T.F. Budinger. ATracer Kinetic Evidence for Abnormal Methyl Metabolism in Schizophrenia.@Biological Psychiatry. Vol. 32, 1992, pp. 1,078B1,090.   "

 ‡  ‡  ‡

LBL-30. Experimental Therapy of Multiple Myeloma with Phosphorus-32, Strontium-89, and Yttrium-90

FROM 1939 TO 1949, twenty-one male and female patients, ranging in age from 29 to 66 years, at the Donner Laboratory, University of California Radiation Laboratory, Berkeley received experimental radioisotope treatments for multiple myeloma.

Nine patients received phosphorus-32 (P³²) and strontium-89 (Sr⁸⁹); 11 received P³² alone; and 1 received colloidal yttrium-90. Levels of the administered activity differed for each patient. Subjects received 1 to 21 oral or intravenous administrations of activity, with total activity ranging from 0.3 to 103 millicuries.

The results of the treatment with P³² or Sr⁸⁹ were no better than results obtained from treatment with x­rays or stilbamidine. The Donner Laboratory was supported by the U.S. Atomic Energy Commission.

References

Lawrence, J.H., and L.R. Wasserman. AMultiple Myeloma: A Study of 24 Patients Treated with Radioactive Isotopes (P³² and Sr⁸⁹).@Annals of Internal Medicine. Vol. 33, 1950, pp. 41B55.  "

LBL-31. Experimental Therapy of Polycythemia Vera Using Phosphorus-32 and X­Rays

BETWEEN 1939 AND 1969, researchers at the Donner Laboratory, University of California Radiation Laboratory, Berkeley treated 181 polycythemia vera patients using intravenously administered phosphorus-32 (P³²) phosphate, or P³² plus x­rays. Doses usually totaled between 15 and 45 millicuries of P³² per patient. X­ray absorbed doses varied greatly between patients.

Excellent results were achieved in many cases, and the life expectancy was extended to nearly normal using this treatment. However, some of the polycythemia vera patients later developed splenic metaplasia and acute leukemia.

Follow-up studies were conducted in the late 1960s to evaluate the overall effectiveness of the therapy and to determine whether there was a relationship between therapy for polycythemia vera and the later incidence of leukemia. These studies indicated that the development of splenic myeloid metaplasia and acute leukemia are part of the evolutionary history of polycythemia vera, and that the incidence of acute leukemia in patients treated with P³² may be a result of prolonged survival rather than a direct effect of radiation dose. The Donner Laboratory was supported by the U.S. Atomic Energy Commission.

References

Lawrence, J.H. The Control of Polycythemia by Marrow Inhibition. Berkeley, CA: University of California Radiation Laboratory, Division of Medical Physics, UCRL-410, August 9, 1949.

Lawrence, J.H., H.S. Winchell, and W.G. Donald. ALeukemia in Polycythemia Vera: Relationship to Splenic Myeloid Metaplasia and Therapeutic Radiation Dose.@Annals of Internal Medicine. Vol. 70, 1969, pp. 763B771.

Wasserman, L.R., J.H. Lawrence, N.I. Berlin, R.L. Dobson, and S. Estern. AThe Bone Marrow Picture in Polycythemia Vera Before and After Treatment with Radioactive Phosphorus.@Acta Medica Scandinavica. Vol. 143, No. 6, 1952, pp. 443B449.  "

LBL-32. Studies of Iodine-131 Uptake in Hypothyroid Children

DURING THE EARLY 1940s, researchers at the University of California Medical School, San Francisco conducted tracer studies, using iodine-131 (I¹³¹) as sodium iodide as tracer, to measure the metabolism of iodine in normal and hypothyroid children.

Ten hypothyroid children and young adults ranging in age from less than 1 year to 19 years served as subjects. The amounts of I¹³¹ administered were about 25 to 50 millicuries, or what the researchers thought to be less than one-fiftieth the amount of radioiodine necessary to produce biologic changes. Uptake was measured with a Geiger counter. Six subjects were administered additional radioiodine a few months later. The results were compared with the radioiodine uptake of three normal children in a separate study.

This study showed that the thyroids of children with hypothyroidism and without goiters concentrated only small amounts of iodine compared to the thyroids of normal children or adults. This work was supported by grants from the Christine Breon Fund for Medical Research and the American Cyanamid Corporation. The principal investigator continued these studies and was supported by the Manhattan Engineer District (MED) during World War II. The University of California Medical School, San Francisco received funding from the MED through a contractual arrangement, and intermittently shared facilities and personnel with the MED-funded predecessors to LBL.

References

Hamilton, J.G., and M.H. Soley. AStudies in Iodine Metabolism of the Thyroid Gland in Situ by the Use of Radio-Iodine in Normal Subjects and in Patients with Various Types of Goiter.@American Journal of Physiology. Vol. 131, 1940, pp. 135B143.

Hamilton, J.G., M.H. Soley, W.A. Reilly, and K.B. Eichorn. ARadioactive Iodine Studies in Childhood Hypothyroidism.@American Journal of Diseases in Children. Vol. 66, 1943, pp. 495B502.

Handwritten Letter. Reilly, W.A. to J.G. Hamilton. January 4, 1949. The Personal Papers of Joseph Hamilton, Bancroft Library, The University of California, Berkeley, California.

Letter. Hamilton, J.G. to W.A. Reilly. January 10, 1950. The Personal Papers of Joseph Hamilton, Bancroft Library, The University of California, Berkeley, California.  "

LBL-33. Studies on Patients Treated with Total-Body X­Ray Irradiation

FROM 1942 TO 1946, researchers at the University of California, San Francisco conducted studies on the blood of patients at the University Hospital who had received therapeutic total-body irradiation (and directed tumor irradiation, in some cases). Patients were selected for radiation therapy by hospital staff physicians and radiation treatments were administered as part of the normal course of therapy for these patients. Only the ancillary blood studies were sponsored by the Manhattan Project.

Sixteen male and 13 female patients ranging in age from 20 to 75 years with metastatic carcinoma, lymphoma, or arthritis were studied. Patients received a series of daily fractional exposures of 5 to 50 roentgens, measured at the skin-surface entry point, with totals ranging from 100 to 300 roentgens. Patient blood samples were studied individually for up to 3 years after treatment. The purpose of this study was to determine whether the analysis of blood changes could be used to indicate occupational radiation exposures in workers on the Manhattan Project.

The studies of blood samples obtained at intervals from the treated patients showed an immediate decrease in the number of white blood cells that are formed in lymphoid tissue, followed by recovery to normal levels during the post-treatment period. Monocytes (very large white blood cells) increased in number during treatment, but returned to normal levels after treatment was completed. Significant deviations in total white blood-cell count were observed during both early and late post-treatment periods. The red blood-cell count and the concentration of hemoglobin decreased during treatment, but recovered during the early post-treatment period. A temporary anemia condition was observed in many patients during the late post-treatment period. These studies were supported by the Health Division of the Metallurgical Laboratory (a Manhattan Project site located in Chicago ).

References

Low-Beer, B.V.A., and R.S. Stone. AHematological Studies in Patients Treated By Total-Body Exposure to X­Rays.@In Industrial Medicine on the Plutonium Project, pp. 338B418. New York: McGraw-Hill, 1951.

Letter. R.S. Stone to A. Gregg. November 4, 1948.  "

LBL-34. Studies Using Radioactive Isotopes of Nitrogen, Argon, Krypton, and Xenon

BETWEEN 1943 AND 1949, the Divisions of Medical Physics and Medicine, and the Radiation Laboratory, University of California, Berkeley conducted studies on the exchange of isotopes of nitrogen, argon, krypton, and xenon gases between the body and the surrounding air. The isotopes used for this research included nitrogen-13, argon-41, krypton-79, krypton-81, krypton-85, xenon-127, xenon-133, and xenon-141. Fifteen subjects ranging in age from 17 to 26 years participated.

Subjects inhaled one of these radioactive gases for 30 to 120 minutes to receive an administered activity of about 0.4 millicurie of each isotope. The subjects were then either placed in a high-altitude chamber to simulate decompression or flown in airplanes to specific altitudes. The hands, legs, and knees of the subjects were placed into specially constructed Geiger counters to measure uptake and elimination rates of the gas isotopes. Counting of the isotopes continued for 1 hour after actual or simulated flight. Many of the subjects exercised at various Aaltitudes@in order to bring on Athe bends,@or the formation of nitrogen bubbles in the blood and tissues characterized by pain in the joints and abdomen. The subjects classified the degree of pain caused by the bends and this information was compared to the subjects=desaturation curves.

This study showed that diffusion plays very little role in the uptake of various gases by tissues, and that the rapidity of gas exchange is dependent on the ability of the blood to carry gas as well as the rate of perfusion of the tissues by blood. This work was supported by the Office of Scientific Research and Development and the Columbia Foundation. The Divisions of Medical Physics and Medicine, and the Radiation Laboratory at the University of California, Berkeley were supported by the U.S. Atomic Energy Commission.

References

Tobias, C.A., H.B. Jones, J.H. Lawrence, and J.G. Hamilton. AThe Uptake and Elimination of Krypton and Other Inert Gases by the Human Body.@The Journal of Clinical Investigation. Vol. 28, No. 6, November 1949, pp. 1,375B1,385.  "

LBL-35. Blood Oxygen Studies in Polycythemia Vera Patients and Normal Subjects Using Colloids of Zirconium-95 and Yttrium-90

IN APPROXIMATELY 1944 to 1947, scientists at the Donner Laboratory, University of California Radiation Laboratory, Berkeley conducted studies on blood oxygen saturation to learn more about the disease polycythemia vera. These studies involved measurements on 74 subjects, 48 of whom were polycythemia vera patients. Among the remainder, 18 were normal, healthy subjects, 4 had hypochromic anemia, and 3 had erythrocytosis (overproduction of red blood cells) and chronic pulmonary or cardiac disease. Blood volumes were determined for some of these subjects using colloids of zirconium-95 (Zr⁹⁵) and yttrium (probably Y⁹⁰, although not stated), or by the use of radioactively labeled red blood cells. No further details were given with regard to specific procedures or amounts of radionuclides administered as part of these studies. All patients also received chest x­rays to exclude polycythemia patients with pulmonary disease.

These studies showed that arterial blood oxygen saturation in polycythemia vera was within normal limits in resting subjects. This research was supported by the International Cancer Research Foundation, the U.S. Public Health Service, and the Sara Welt Fund. The Donner Laboratory was supported by the U.S. Atomic Energy Commission.

References

Dobson, E.L., J.W. Gofman, H.B. Jones, L.S. Kelly, and L.A. Walker. AStudies with Colloids Containing Radioisotopes of Yttrium, Zirconium, Columbium, and Lanthanum. II. The Controlled Selective Localization of Radioisotopes of Yttrium, Zirconium, and Columbium in the Bone Marrow, Liver, and Spleen.@Journal of Laboratory and Clinical Medicine. Vol. 34, No. 3, pp. 305B312.

Gofman, J.W. AStudies with Colloids Containing Radioisotopes of Yttrium, Zirconium, Columbium, and Lanthanum. I. The Chemical Principles and Methods Involved in Preparation of Colloids of Yttrium, Zirconium, Columbium, and Lanthanum.@Journal of Laboratory and Clinical Medicine. Vol. 34, No. 3, pp. 297B304.

Wasserman, L.R., R.L. Dobson, and J.H. Lawrence. ABlood Oxygen Studies in Patients with Polycythemia and in Normal Subjects. Journal of Clinical Investigation. Vol. 28, 1949, pp. 60B65.  "

LBL-36. Experimental Breast Cancer Treatment Studies Using Phosphorus-32

BETWEEN 1945 AND 1954, researchers at the University of California Medical School, San Francisco treated 89 breast cancer patients with phosphorus-32 (P³²) in combination with surgery and x­ray therapy. The treatment protocol included intravenous administration of 20 to 30 microcuries of P³² as sodium hypophosphate per kilogram of body weight, two or three times a week over 2 to 4 weeks. In addition, the treatment included local x­ray exposure up to 4,000 roentgens within 35 days. Total administered activity P³² ranged from 5.0 to 25.2 millicuries. In 1945 and 1946, eight additional breast cancer patients were treated. Treatments were suspended in 1947 because of concern regarding possible subsequent radiation-induced hematologic effects of internally deposited P³². Treatments were resumed in 1951 after no evidence of adverse effect had been observed among the previously treated patients, and an additional 81 subjects were treated over the next 4 years.

Follow-up of the treated patients through 1954 showed that 5 of the 8 patients treated during 1945 and 1946 were still alive, as were 75 of the 85 treated in 1951 or later.

The researchers concluded that further investigations and an expanded clinical experience were needed before a definitive conclusion could be reached about the success of this experimental treatment method. The University of California Medical School, San Francisco, received funding from the U.S. Atomic Energy Commission (AEC) through a contractual arrangement, and intermittently shared facilities and personnel with the AEC-funded predecessors to Lawrence Berkeley Laboratory.

References

Bell, H.G., and B.V.A. Low-Beer. ACancer of the Breast. A Preliminary Report on a New Approach to the Problem.@Journal of the American Geriatrics Society. Vol. 3, June 1955, pp. 396B398.

Low-Beer, B.V.A., and H.G. Bell. ASurgical and Radiation Treatment of Carcinoma of the Breast: A New Concept.@The American Journal of Roentgenology, Radium Therapy and Nuclear Medicine. Vol. 75, No. 6, June 1956, pp. 1,162B1,168.

Cancer Board Meeting Minutes, June 10 1953. Special Collections, The Library, University of California. Boldrey, Edwin Barkley, Papers, MSS 88-56, Carton 6. Folder ACancer Board 1953B54.@ "

LBL-37. Experimental Thyroid Cancer Treatment Using Iodine-131

BETWEEN 1945 AND 1954, researchers in the Department of Radiology, University of California Medical School, San Francisco evaluated the use of iodine-131 (I¹³¹) in the treatment of thyroid cancer. The cases of 124 patients with confirmed primary thyroid cancer were studied.

Most patients had received 1 to 2 millicuries of I¹³¹ to test their thyroid function before surgery. Of these patients, 101 showed no detectable tumor or I¹³¹ uptake after surgery. Among these subjects, 14 received 25 to 50 millicuries of I¹³¹ on one or two occasions; were then given thyroid extract; and were later checked for recurrence or development of radiation-induced effects. The 23 patients with inoperable thyroid cancer received 100 millicuries of I¹³¹. This was administered once monthly until there was no evidence of tumor tissue as indicated by the absence of I¹³¹ uptake, or until adverse effects of the treatment were observed.

The results showed that treatment of thyroid cancer with I¹³¹ often was not effective. Radiation-induced depression of all cell types in the circulating blood and bone marrow was evident to widely varying degrees, with the greatest effect being observed at the highest total I¹³¹ activity. However, the magnitude of the effect was not always correlated with the level of I¹³¹ activity. This research was funded by the U.S. Atomic Energy Commission.

References

Aggeler, P.M. The Effect of I¹³¹ On the Bone Marrow. San Francisco: University California at San Francisco, U.S. Atomic Energy Commission Report, UCSF-8. January 1954, pp. 38B57.

Alexford, A.R., and L. Berman. AThe Bone Marrow in Hyperthyroidism and Hypothyroidism.@Blood: The Journal of Hematology. Vol. 6, 1951, pp. 436B453.

Sheline, G.E., and E.R. Miller. AStudies with Radioiodine. VI. Evaluation of Radioiodine Treatment of Carcinoma of the Thyroid Based on the Experience at the University of California from 1938 to 1954.@Radiology. Vol. 69, 1957, pp. 527B545.

Miler, R.R., M.E. Dailey, A.V. Holmes, G.L. Alexander, and G.E. Sheline. AStudies with Radioiodine. I. Function and Rate of I¹³¹ Uptake of Thyroid.@Radiology. Vol. 57, No. 1, July 1951, pp. 37B47.  "

LBL-38. Metabolism and Effects of Iodine-131

A STUDY WAS CONDUCTED in 1947 and 1948 at the Radiation Laboratory, University of California, Berkeley to learn more about the effects of iodine-131 (I¹³¹) and its metabolism in normal subjects and patients with thyroid disorders. The objective of this study was to measure the uptake of I¹³¹ in the thyroid and the rate of its excretion in urine in order to determine the metabolism of iodine and its concentration in other sites in the body. Subjects included a few healthy physicians from the University of California Hospital, a series of patients with thyroid nodules but otherwise-normal thyroid function, and a group of subjects with confirmed thyroid cancer.

The normal subjects and patients with nodules received an oral dosage of 0.25 millicurie of I¹³¹. Subjects treated for hyperthyroidism received 0.25 to 4.0 millicuries or up to 12 millicuries over an extended period of time. Subjects with thyroid cancer received 2 millicuries at two different times, and one patient received 59 millicuries. Measurements were made at various times to measure I¹³¹ activity in the subjects=thyroids and urine.

Normal thyroids were found to retain between 5 and 35 percent of the ingested I¹³¹. This study also showed that the uptake of iodine in the thyroid was related to the degree of thyroid function. No adverse clinical effects of radioiodine were observed in most patients, including the patient receiving the greatest amount of I¹³¹. This work was supported by the U.S. Atomic Energy Commission.

References

Miller, E.R. AMetabolism and Effects of Radio-Iodine (I¹³¹).@Medical and Health Divisions Quarterly Report. Berkeley, CA: University of California Radiation Laboratory, UCRL-41, October 1947BJanuary 1948, pp. 37B52.  "

LBL-39. Studies Using Phosphorus-32 and Other Radioisotopes

FROM 1948 TO 1949, at the Laguna Honda Home in San Francisco (a hospital for destitute patients), researchers from the Laboratory of Experimental Oncology, University of California, conducted a variety of studies using phosphorus-32 (P³²) and other radioisotopes. Sixty-one patients participated as subjects.

Three patients underwent experimental therapy using various radioactive compounds. In the Laboratory=s Isotope Unit, 43 patients participated in uptake, excretion, and tissue assay studies involving P³². Seven patients participated in iodine-131 uptake studies. Uptake, excretion, and tissue assay studies were conducted on five patients using zirconium-95 and niobium-95, two patients using copper-64, and one patient using gallium-72. The research fellows working in the Isotope Unit were funded by the National Cancer Institute and the U.S. Atomic Energy Commission.

References

Laboratory of Experimental Oncology Annual Report 1948B1949.San Francisco: University of California at San Francisco. Special Collections Library, San Francisco Record Series: School of Medicine, Committee Reports 1917B1957, Carton 1, Folder ASchool of Medicine Research Committee 3.@ "

LBL-40. Studies of Electric Potentials in the Stomach Using Sodium-24

FROM 1948 TO 1949, researchers at the University of California Medical School, San Francisco investigated the electric potentials across cells in the lining of the stomach in order to better understand their relationship with physiologic processes in the stomach. Two patients of the Laboratory of Experimental Oncology at the Laguna Honda Home participated as subjects. Both received open surgical incisions in the stomach wall through which samples of stomach juices and electric measurements were obtained.

An unspecified amount of sodium-24 (Na²⁴) was administered by intravenous injection to each patient to determine the time between injection and the appearance of the Na²⁴ in the stomach. This interval was found to be less than 3 minutes. Attempts to correlate sodium and hydrogen ions were unsuccessful.

The studies were not completed. This work was funded by the National Cancer Institute through the University of California School of Medicine. The University of California Medical School, San Francisco, received funding from the U.S. Atomic Energy Commission (AEC) through a contractual arrangement, and intermittently shared facilities and personnel with the AEC-funded predecessors to Lawrence Berkeley Laboratory.

References

Laboratory of Experimental Oncology Annual Report 1948B1949. San Francisco: University of California at San Francisco, 1949, pp. 21B22. Special Collections Library, San Francisco Record Series: School of Medicine, Committee Reports 1917B1957, Carton 1, Folder ASchool of Medicine Research Committee 3.@  "

LBL-41. Studies of Methionine Metabolism Using Sulfur-35 as Tracer

IN 1948 AND 1949, researchers at the University of California Medical School, San Francisco; the Division of Biochemistry, University of California, Berkeley; the Metabolic Research Unit and the Department of Medicine, U.S. Naval Hospital, Oakland; and the Department of Chemistry, Mills College conducted collaborative studies on methionine metabolism using sulfur-35 (S³⁵) as a tracer of the metabolic processes involved. The purpose of these studies was to determine whether methionine was metabolized differently in patients with chronic liver disease, idiopathic hypoproteinemia (an abnormal decrease in the amount of protein in the blood), or Cushing=s syndrome.

Amounts of S³⁵-labeled DL-methionine ranging from 25 to 100 microcuries were administered by intravenous injection to three normal males, ages 19, 20, and 26 years; and to five patients with chronic illnesses, four males aged 22 to 43 years and one 39-year-old female. All subjects fasted before and after the injection. Blood, urine, and fecal samples were collected and analyzed for S³⁵ to determine the turnover rate of methionine into plasma protein and the rate of excretion.

This study showed that the three patients with chronic liver damage had a lower rate of incorporation of the S³⁵-labeled methionine. The patient with Cushing=s syndrome showed a pattern of metabolism similar to that of the control subjects, and the patient with idiopathic hypoproteinemia had an excessive rate of protein plasma turnover. This work was supported by the U.S. Navy and the Office of Naval Research, the latter under a contract with the University of California. The University of California Medical School, San Francisco, received funding from the U.S. Atomic Energy Commission (AEC) through a contractual arrangement, and intermittently shared facilities and personnel with the AEC-funded predecessors to Lawrence Berkeley Laboratory.

References

Kinsell, L.W., S. Margen, H. Tarver, J. McB. Frantz, and E.K. Flanagan. AStudies in Protein Metabolism with the Aid of S³⁵-Labeled Methionine. Journal of Clinical Investigation. Vol. 28, 1949, p. 793.

Kinsell, L.W., S. Margen, H. Tarver, J. McB. Frantz, E.K. Flanagan, M.E. Hutchin, G.D. Michaels, and D.P. McCallie. AStudies in Methionine Metabolism. III. The Fate of Intravenously Administered S³⁵-Labeled Methionine in Normal Adult Males, in Patients with Chronic Hepatic Disease, >Idiopathic=Hypoproteinemia and Cushing=s Syndrome.@Journal of Clinical Investigation. Vol. 29, 1950, pp. 238B250.  "

LBL-42. X­Ray Irradiation of the Normal Pituitary Gland During Conventional Cancer Therapy

BETWEEN 1948 AND 1949, at the Laguna Honda Home (a hospital for destitute patients) in San Francisco, the Laboratory of Experimental Oncology, University of California, conducted a study on the effects of adjuvant x­ray irradiation of the normal pituitary gland, during treatment of cancers in other tissues (e.g., skin melanoma, breast, and prostate).

The study was designed to deliver 8,000 to 10,000 rads to the subject=s pituitary gland in hopes that the reduced secretion of pituitary hormones would benefit the cancer treatment. At least one patient, a 60-year-old female with breast cancer and metastases of the skin, was treated by irradiation of her pituitary gland. Clinical laboratory indicators were evaluated to determine whether hypophysectomy by irradiation would be more effective than surgical removal of the pituitary gland.

Follow-up results of this study were apparently not reported. The Laboratory of Experimental Oncology at Laguna Honda Home was funded by the National Cancer Institute. The study was performed with support of a U.S. Atomic Energy Commission research fellow.

References

Laboratory of Experimental Oncology Annual Report 1948B1949. San Francisco: University of California at San Francisco, 1949, pp. 16B17 Special Collections Library, San Francisco Record Series: School of Medicine, Committee Reports 1917B1957, Carton 1, Folder ASchool of Medicine Research Committee 3.@ "

LBL-43. Experimental X­Ray Irradiation of the Pituitary in Patients with Melanoma or Hormonally Influenced Tumors

IN 1949 OR 1950, at the Laguna Honda Home in San Francisco (a hospital for destitute patients), researchers from the Laboratory of Experimental Oncology, University of California, San Francisco collaborated in a study of pituitary irradiation and its effect on advanced melanoma and breast cancer. The purpose of this experimental therapy was to induce hypophysectomy (removal or destruction of the pituitary) with radiation. It was hoped that this technique would interrupt the influence of pituitary hormones, which were believed to stimulate tumor growth.

Three female patients, two with advanced carcinoma of the breast and one with disseminated melanoma, received between 8,500 and 10,000 rads of x­ray radiation to their pituitary glands. However, no visible changes in the pituitary or in the clinical parameters under the control of pituitary hormones were apparent during initial observation.

Preliminary conclusions were that the pituitary is extremely resistant to x­rays. The project was sponsored by the Cancer Research Institute, School of Medicine, University of California, San Francisco, and partially funded by grants from the National Cancer Institute. It was also supported by the U.S. Atomic Energy Commission.

References

Application for Cancer Funds SF-1-50. Renewal (for 4th fiscal year) Report, Laboratory of Experimental Oncology, Laguna Honda Home, San Francisco, California, March 6, 1950, File Code 19-14-5, Carton 1/3, Folder AApplications for Cancer Funds.@ "

LBL-44 Blood Volume Studies Using Radioactive Phosphorus-32 as Tracer

FROM 1949 TO 1950, researchers at the Donner Laboratory, University of California Radiation Laboratory, Berkeley and at the Highland Alameda County Hospital, Oakland conducted studies on blood volume and the oxygen carrying capacity of the blood, using phosphorus-32 (P³²). The labeling technique consisted of incubating 5 milliliters of the patient=s blood with 500 microcuries of P³² (as sodium or orthophosphate in saline) for 2 hours. After additional processing and washing, the blood cells were injected into the same patient.

The purpose of one study was to determine the relation between the hematocrit (the percentage of the blood volume occupied by cells) and the total red cell volume, and to investigate the pathologic physiology of the blood volume in leukemia. Blood volumes were determined with P³²-labeled red blood cells in 24 cases of chronic lymphatic leukemia and 17 cases of chronic myelogenous leukemia, using hospital patients as subjects. Results showed that the variation of total red cell volume for a given hematocrit is so large that it is of negligible value for the prediction of the total red cell volume in either normal subjects or patients with chronic leukemia. Determination of the blood volume is of considerable value in the treatment of chronic leukemia patients.

The purpose of the second study was to determine normal blood volume and plasma volume in healthy adult women, using the same technique of labeling blood cells with P³². The 16 healthy volunteers ranged in age from 22 to 48 years. Results of these studies showed that blood volumes in the males did not differ from those in a similar normal male population, despite differences in percentages of body fat.

A third study was conducted to determine blood loss and red cell turnover rates (in terms of cubic centimeters per kilogram of body weight) during thoracic surgery. Twenty-seven patients ranging in age from 21 to 57 years participated as subjects. The patients=surgeries were conducted in association with tuberculosis therapy. This study provided data on blood loss for various thoracic surgical procedures and demonstrated the feasibility of using this technique to make accurate blood volume determinations. It is of considerable clinical value to know the blood volume in thoracic surgical patients.

A study involving 12 prisoners who were evaluated for total red blood-cell volume and plasma volume was mentioned; however, details were not provided in the supporting documents. These studies were supported in part by the U.S. Public Health Service and the U.S. Atomic Energy Commission.

References

Berlin, N.I., J.H. Lawrence, and J. Gartland. AThe Blood Volume in Chronic Leukemia as Determined by P³²-Labeled Red Blood Cells.@Journal of Laboratory and Clinical Medicine. Vol. 36, 1950, pp. 435B439.

Berlin, N.I., G.M. Hyde, R.J. Parson, J.H. Lawrence, and S. Port. ABlood Volume of the Normal Female as Determined with P³²-Labeled Red Blood Cells.@In Proceedings of the Society of Experimental Biology and Medicine. Vol. 76, 1951, pp. 831B832.

Berlin, N.I., D.F. Rowles, G.M. Hyde, R.J. Parsons, P.C. Samson, and S. Port. AThe Blood Volume and Blood Turnover in Thoracic Surgery as Determined by P³²-Labeled Red Blood Cells.@Surgery, Gynecology, and Obstetrics. Vol. 92, 1951, pp. 712B716.  "

LBL-45. Studies on the Distribution of Gases, Water, and Electrolytes in the Human Body Using Carbon-11, Sodium-24, and Iodine-131

DURING THE LATE 1940s AND EARLY 1950s, studies on carbon monoxide metabolism and the in vivo analysis of human body composition were conducted by researchers at the Donner Laboratory, University of California Radiation Laboratory, Berkeley. Tracer doses were administered during studies to both normal subjects and subjects with various diseases.

One specific objective of the studies was to identify the function of the liver in carbon monoxide metabolism. Carbon monoxide labeled with carbon-11 (C¹¹) was employed for this purpose. These studies measured the rate of equilibration of (stable) heavy water (deuterium oxide [D₂O]) and sodium-24 (Na²⁴) in normal subjects following the injection of a saline solution labeled with Na²⁴. Samples of plasma, drawn at intervals following the injection, were used to measure total-body water and sodium content.

Some of these studies involved measuring the total sodium space and total-body sodium in older subjects, particularly patients with cardiac edema and other health problems, for comparison to normal subjects. The subjectsCcardiac patients and normal volunteers (including 10 young normal adults, 13 older adults, 11 elderly adults with cardiovascular disease, and 20 elderly adults with congestive failure and edema)Cwere administered 100 microcuries of Na²⁴ in isotonic sodium chloride. Blood samples were later drawn and counted for Na²⁴.

Differences were found in total sodium space between young and old normal adults. These differences corresponded to an increase in age, and a marked increase in cardiac edema. Additional studies were made of Na²⁴ clearance from a limb as measured by in vivo counting in normal subjects and cardiac patients. Iodine-131 was also used for some of these studies to determine whether impaired circulation and altered fluid spaces had any effect on the Na²⁴ distribution curve. This research was supported in part by a grant from the Office of Naval Research and by the U.S. Atomic Energy Commission.

References

Warner, G.F., E.L. Dobson, C.E. Rodgers, M.E. Johnston, and N. Pace. AThe Measurement of Total Sodium Space and Total-Body Sodium in Normal Individuals and in Patients with Cardiac Edema.@Circulation. Vol. 5, 1952, pp. 915B919.

Letter. J.H. Lawrence to President R.G. Sproul. September 18, 1947. University of California, University Archives, Office of the President, Correspondence and Papers, CU-5, Carton 713, Folder 748 #4.

Correspondence. University of California to Office of Naval Research. MayBDecember 1949. University of California, University Archives, Office of the President, Correspondence and Papers, CU-5, Carton 760, Folder 748-L.  "

LBL-46. Total-Body Water Studies Using Tritium as a Tracer

DURING THE EARLY 1950s, researchers at the Donner Laboratory, University of California Radiation Laboratory, Berkeley conducted studies on total-body water measurements using tritium (H³) as a tracer. Thirty-seven patients at the Highland Alameda County Hospital, ranging in age from 30 to 80 years, and 20 normal male volunteers, ranging in age from 20 to 56 years, from San Quentin Prison participated as subjects.

Subjects were intravenously administered 2 millicuries of water labeled with H³. Blood samples were drawn at intervals of 2, 4, and 6 hours and the H³ activity in the plasma was measured.

This study showed that total-body water varies greatly from individual to individual, reflecting the variation in body fat. In pathologic states, where lean body mass cannot be assumed to remain constant in composition, body water determinations are of limited value without a method for measuring body fat. This work was supported by the U.S. Atomic Energy Commission.

References

Prentice, T.C., W. Siri, N.I. Berlin, G.M. Hyde, R.J. Parsons, E.E. Joiner, and J.H. Lawrence. AStudies of Total-Body Water with Tritium.@Journal of Clinical Investigation. Vol. 31, 1952, pp. 412B418.  "

LBL-47. Liver Blood Flow Studies Using Phosphorus-32 as a Tracer

DURING THE EARLY 1950s, scientists at the Donner Laboratory, University of California Radiation Laboratory, Berkeley studied the blood flow through the liver by measuring the removal rate of colloidal particulate matter from the blood stream. In this study, the particulate matter was colloidal chromic phosphate labeled with phosphorus-32 (P³²).

Subjects for this study were 29 healthy fasting men between the ages of 20 and 26. Each received an intravenous injection of colloidal chromic phosphate containing 2 to 4 microcuries of P³². Subsequently, blood samples were drawn at frequent intervals and measured for blood volume and specific activity.

The study found the average particulate disappearance rate corresponded to a liver blood flow of 1.5 to 1.8 liters per minute. This experiment was supported by the Office of Naval Research and the U.S. Atomic Energy Commission.

References

Dobson, E., G. Warner, C. Finney, and M. Johnston. AThe Measurement of Liver Circulation by Means of the Colloid Disappearance Rate.@Circulation. Vol. 7, May 1953, pp. 690B695.  "

LBL-48. Blood Volume Studies in Cirrhosis Using Phosphorus-32BLabeled Red Blood Cells

DURING THE EARLY 1950s, researchers at the Donner Laboratory, University of California Radiation Laboratory, Berkeley and at the Highland Alameda County Hospital, Oakland conducted studies on blood volume in cirrhosis patients using phosphorus-32 (P³²).

Twenty-eight patients with portal cirrhosis of the liver participated as subjects. Blood volume in each subject was measured using an established technique that included labeling 5 milliliters of blood drawn from the patient with 500 microcuries of P³², and reinjecting 1 milliliter.

The results of these studies showed that cirrhosis patients may exhibit various levels of total blood volume, red cell volume, or plasma volume. The study also showed that neither red cell volume nor plasma volume can be predicted from total cell volume in a blood sample. This work was supported in part by the U.S. Atomic Energy Commission.

References

Berlin, N.I., J.H. Lawrence, and J. Gartland. AThe Blood Volume in Chronic Leucemia as Determined by P³²-Labeled Red Blood Cells.@Journal of Laboratory and Clinical Medicine. Vol. 36, 1950, pp. 435B439.

Hyde, G.M., N. Berlin, R.J. Parsons, J.H. Lawrence, and S. Port. AThe Blood Volume in Portal Cirrhosis as Determined by P³²-Labeled Red Blood Cells.@Journal of Laboratory and Clinical Medicine. Vol. 39, 1952, pp. 347B358.  "

LBL-49. Studies of the Metabolism of Tritium-Labeled Cholesterol

DURING THE EARLY 1950s, researchers at the Donner Laboratory, University of California Radiation Laboratory, Berkeley conducted cholesterol metabolism studies using tritium (H³) as a tracer. The purpose of these studies was to investigate the relationship between dietary fat (lipids) and the development of atherosclerosis (hardening of the arteries) by tracing the absorption and turnover of ingested cholesterol in various compartments of the blood.

Four patients ranging in age from 42 to 69 years, all of whom had some degree of atherosclerosis, participated as subjects. Three were orally administered H³-cholesterol dissolved in warm vegetable oil emulsified into whole milk. The fourth patient received the H³-cholesterol in crystalline form dispersed in milk. The specific activity of the ingested H³ varied from 0.48 to 1.07 millicuries per gram of cholesterol (depending on the preparation used). Blood and tissue cholesterol samples were assayed to determine the rate and magnitude of the appearance of ingested cholesterol in the various blood compartments.

The studies showed that cholesterol absorption in man is slow and inefficient. The Donner Laboratory was supported by the U.S. Atomic Energy Commission.

References

Biggs, M.W., D. Kritchevsky, D. Colman, J.W. Gofman, H.B. Jones, F.T. Lindgren, G. Hyde, and T.P. Lyon. AObservations on the Fate of Ingested Cholesterol in Man.@Circulation. Vol. 6, September 1952, pp. 359B366.  "

LBL-50. Study of Sodium-24 Metabolism in Normal Individuals and Patients with Ascites

DURING THE EARLY 1950s, the Departments of Physiology and Medicine, University of California Medical School, San Francisco; the University of California Medical Service of the San Francisco Hospital; the San Francisco Department of Public Health; and the Donner Laboratory, University of California Radiation Laboratory, Berkeley conducted collaborative studies of sodium metabolism in humans using sodium-24 (Na²⁴). The purpose of the studies was to determine the Asodium space@and body sodium content, exchangeable with Na²⁴, in normal adult subjects with no history of electrolyte or fluid imbalance, and in patients with ascites (fluid accumulation in the abdominal cavity) due to liver damage associated with advanced chronic hepatitis.

Study subjects included 15 normal (13 male and 2 female) hospital convalescents ranging in age from 42 to 85 years and with no history of electrolyte or fluid imbalance who served as study controls; and 20 cirrhotic patients, 15 males and 5 females, ranging in age from 38 to 69 years with ascites. Each subject received an injection of approximately 100 microcuries of Na²⁴. Blood samples were drawn 12, 24, and 40 hours after the injection and analyzed.

The studies showed sodium space and body sodium content of the patients with ascites were markedly higher than those of normal subjects and that the increase was roughly proportional to the degree of ascites clinically observed in the patient. This work was supported by the Office of Naval Research and the U.S. Atomic Energy Commission.

References

Warner, G., N. Sweet, and E. Dobson. A>Sodium space=and body sodium content, exchangeable with sodium-24, in normal individuals and patients with ascites.@Circulation Research. Vol. 1, 1953, pp. 486B490.  "

LBL-51. Measurement of Total ASodium Space@and Total-Body Sodium Using Sodium-24 as a Tracer

DURING THE EARLY 1950s, researchers at the Donner Laboratory, University of California Radiation Laboratory, Berkeley; the Department of Physiology, University of California, Berkeley; and the University of California Medical Service Hospital, San Francisco conducted a study to measure the total Asodium space@and total-body sodium contents using sodium-24 (Na²⁴) as a tracer.

Four groups of adult male subjects participated, including 10 normal subjects, ages 21 to 29; 13 normal subjects, ages 42 to 83; 10 subjects ages, 40 to 75 with cardiovascular disease; and 14 subjects ages, 40 to 72 with cardiovascular disease, congestive heart failure, and edema. Each subject was intravenously administered approximately 100 microcuries of Na²⁴. Activity was measured in a single blood sample drawn 24 hours after administration.

The results of the study showed an increase in sodium content consistent with age. In subjects with congestive heart failure and edema, there was a marked increase in total sodium space and total-body sodium. This work was supported by the Office of Naval Research and the U.S. Atomic Energy Commission.

References

Warner, G.F., E.L. Dobson, C.E. Rodgers, M.E. Johnston, and N. Pace. AThe Measurement of Total >Sodium Space=and Total-Body Sodium in Normal Individuals and in Patients with Cardiac Edema.@Circulation. Vol. 5, June 1952, pp. 915B919.  "

LBL-52. Study of the Effects of Injection Volume on Intramuscular Sodium Clearance Rates Using Sodium-24

DURING THE EARLY 1950s, researchers from the Donner Laboratory, University of California Radiation Laboratory, Berkeley and the Department of Physiology, University of California, Berkeley conducted studies to measure the effect of injection volume on the intramuscular clearance rate of sodium using sodium-24 (Na²⁴). The purpose of this study was to develop a practical method for measuring regional blood flow.

Six normal males between the ages of 20 and 30 years each received intramuscular injections of 5 microcuries of Na²⁴ as isotonic sodium chloride into the calf muscles of both legs. The volume of the injection into one leg was 1.0 milliliter, while the volume of the injection into the other leg varied from 0.005 to 1.0 milliliters. Immediately after injection, external counters measured the activity remaining at the injection sites.

These studies showed that the rate of clearance increased as the volume of the injection decreased. This work was supported by the Office of Naval Research and the U.S. Atomic Energy Commission.

References

Warner, G.F., E.L. Dobson, N. Pace, M.E. Johnston, and C.R. Finney. AStudies of Human Peripheral Blood Flow: The Effect of Injection Volume on the Intramuscular Radiosodium Clearance Rate.@Circulation. Vol. 8, November 1953, pp. 732B734. "

LBL-53. Experimental Treatment of Bladder Tumors Using Cobalt-60 Beads

DURING THE EARLY 1950s, physicians in the Departments of Surgery, Urology, and Radiology, at the University of California Medical School, San Francisco treated 35 bladder cancer patients with radiocobalt beads.

Cobalt-60 (Co⁶⁰) beads, ranging in total administered activity from 20 to 90 millicuries per patient, were inserted into the bladder cavity. The beads delivered estimated doses of 5,000 to 6,000 rads to bladder wall tissue over a 7- to 10-day period. Some of the patients also received approximately 3,500 rads of x­ray radiation over a 35- to 40-day period.

The results of the study showed that noninfiltrating lesions could be treated successfully, but infiltrating lesions were only temporarily arrested. The University of California Medical School, San Francisco received funding from the U.S. Atomic Energy Commission (AEC) through a contractual arrangement, and intermittently shared facilities and personnel with the AEC-funded predecessors to Lawrence Berkeley Laboratory.

References

Hinman, F. Jr., J.W. Schulte, and B.V.A. Low-Beer. AFurther Experience with Intracavitary Radiocobalt for Bladder Tumors.@The Journal of Urology. Vol. 73, No. 2, February 1955, pp. 285B291.

Schulte, J.W., F. Hinman Jr., and B.V.A. Low-Beer. ARadiocobalt in the Treatment of Bladder Tumors.@The Journal of Urology. Vol. 67, No. 6, June 1952, pp. 916B924.  "

LBL-54. Red Blood-Cell Studies in Leukemia Patients Using Carbon-14BLabeled Glycine

DURING THE EARLY 1950s, researchers at the Donner Laboratory, University of California Radiation Laboratory, Berkeley conducted studies of the life span of red blood cells in chronic leukemia using carbon-14 (C¹⁴)Blabeled glycine.

Eight chronic leukemia patients, ranging in age from 24 to 68 years, participated as subjects. Each was intravenously administered approximately 100 microcuries of C¹⁴. A blood sample was drawn and measured for activity.

These studies showed that non-hemorrhage-induced anemia in leukemia is the result of a shortened life span of the red blood cells. This work was supported by the U.S. Atomic Energy Commission.

References

Berlin, N.I., J.H. Lawrence, and H.C. Lee. AThe Pathogenesis of the Anemia of Chronic Leukemia: Measurement of the Life Span of Red Blood Cells Glycine-2-C¹⁴.@Journal of Laboratory and Clinical Medicine. Vol. 44, December 1954, pp. 860B874.  "

LBL-55. Study of the Effect of Thyrotropic Hormone Using Iodine-131

DURING THE EARLY 1950s, researchers at the University of California Pediatric Clinic, San Francisco conducted a study on the effect of thyrotropic hormone in children as measured by an increase in iodine-131 (I¹³¹) uptake. The purpose of the study was to differentiate primary from secondary hypothyroidism (abnormally low thyroid activity) in infancy and childhood.

Five euthyroid (with normal thyroid function) children, and six hypothyroid children, ranging in age from 1 to 15 years, participated as subjects. Each subject was administered 15 to 40 microcuries of I¹³¹ either orally or through a polyethylene stomach tube. Uptake was measured after 24 hours. Thyrotropic hormone therapy was then initiated and continued over a period of 48 hours, after which I¹³¹ uptake was again measured.

This study showed an increase in I¹³¹ uptake in euthyroid children, little or no difference in hypothyroid children assumed to have primary end-organ deficiency, and an increase in uptake in hypothyroid children with collateral signs of pituitary insufficiency. The results suggested a method for differentiating primary from secondary hypothyroidism in childhood. This work was supported by the University of California, the Playtex Park Research Institute, and the U.S. Atomic Energy Commission.

References

Pickering, D.E., and E.R. Miller. AThyrotropic Hormone in Infants and Children.@American Medical Association Journal of Diseases in Children. Vol. 85, No. 2, 1953, pp. 135B140.  "

LBL-56. Blood Volume Studies in Cancer Using Phosphorus-32

DURING THE EARLY 1950s, ,researchers at the Donner Laboratory, University of California Radiation Laboratory, Berkeley and at the Highland Alameda County Hospital, Oakland conducted studies on blood volume in cancer patients using phosphorus-32 (P³²). The purpose of this study was to determine whether advanced stages of cancer were associated with anemia.

Sixty-six cancer patients, including both males and females ranging in age from 24 to 86 years, participated as subjects. Blood volume in each subject was measured using a technique involving the labeling of 5 milliliters of blood drawn from the patient with 500 microcuries of P³², and reinjecting 1 milliliter of labeled blood into the patient.

These studies indicated that 32 percent of the patients were anemic, possibly caused by a shortened red cell life span, as in leukemia. This study was supported by the U.S. Public Health Service. The Donner Laboratory was supported by the U.S. Atomic Energy Commission.

References

Berlin, N.I., G.M. Hyde, R.J. Parson, and J.H. Lawrence. AThe Blood Volume in Cancer.@Cancer. Vol. 8, No. 4, 1955, pp. 796B802.  "

LBL-57. Blood Volume Studies in Pregnancy Using Phosphorus-32

DURING THE EARLY 1950s, researchers at the Donner Laboratory, University of California Radiation Laboratory, Berkeley and at the Highland Alameda County Hospital, Oakland investigated the anemia associated with pregnancy to better understand the relationship between anemia, blood volume, and total red cell volume. Blood volumes were determined using phosphorus-32 (P³²)-labeled red blood cells in 181 women. These included 157 pregnant patients and 34 postpartum patients.

Blood volume in each subject was measured using a technique that included labeling 5 milliliters of blood drawn from the patient with 500 microcuries of P³², and reinjecting 1 milliliter. Blood samples were obtained at various times after injection, before and after delivery.

The results of these studies showed a true anemia during the first and second trimesters of pregnancy, confirmed a progressive increase of plasma volume up to the 9th month of pregnancy, and showed a decrease in blood volume at delivery. This work was supported in part by the U.S. Atomic Energy Commission.

References

Berlin, N.I., C. Goetsch, G.M. Hyde, and R.J. Parsons. AThe Blood Volume in Pregnancy as Determined with P³²BLabeled Red Blood Cells.@Surgery Gynecology and Obstetrics. Vol. 94, 1952, pp. 173B176.  "

LBL-58. Blood Volume Studies in Pre-Eclamptic Patients Using Phosphorus-32

DURING THE EARLY 1950s, researchers at the Donner Laboratory, University of California Radiation Laboratory, Berkeley and at the Highland Alameda County Hospital, Oakland conducted studies on blood volume in women with pre-eclampsia (hypertension due to pregnancy) using phosphorus-32 (P³²). Eight women in the last trimester of pregnancy and diagnosed with pre-eclampsia participated as subjects.

Blood volume in each subject was measured using a technique that included labeling 5 milliliters of blood that was drawn from the patient, with 500 microcuries of P³², and reinjecting 1 milliliter.

These studies showed a reduction in total blood, red cell, and plasma volumes in participating patients. This work was supported in part by the U.S. Atomic Energy Commission.

References

Berlin, N.I., J.H. Lawrence, and J. Gartland. AThe Blood Volume in Chronic Leucemia as Determined by P³²-Labeled Red Blood Cells.@Journal of Laboratory and Clinical Medicine. Vol. 36, 1950, pp. 435B439.

Berlin, N.I., G.M. Hyde, J.H. Lawrence, R.J. Parsons, and S. Port. AThe Blood Volume in Pre-Eclampsia as Determined With P³²-Labeled Red Blood Cells.@Surgery Gynecology and Obstetrics. Vol. 92, 1951, pp. 21B22.  "

LBL-59. Lipid Metabolism Studies Using Tritium-Labeled Cholesterol

DURING THE EARLY 1950s, scientists at the Donner Laboratory, University of California Radiation Laboratory, Berkeley conducted studies on lipid metabolism using tritium (H³) as a tracer. The purpose of these studies was to demonstrate a quantifiable metabolic defect in lipid metabolism.

The subjects of these studies were 10 hospital patients ranging in age from 34 to 52 years and included 2 with elevated cholesterol; 3 with clinical atherosclerosis; and 3 normal, healthy subjects. Each was administered 0.55 to 0.77 millicurie of cholesterol labeled with H³ dissolved in warm vegetable oil, emulsified into whole milk, and mixed together with ice cream. Serum cholesterol measurements were made 1, 7, and 14 days after ingestion by analysis for H³.

This study showed that patients with abnormal serum lipoprotein spectra carry a greater fraction of their newly absorbed cholesterol in the esterified form (an oxygen-linked form of cholesterol commonly found in the body) than do subjects with normal serum lipoprotein spectra. This research was supported by the U.S. Atomic Energy Commission.

References

Biggs, M.W., and D. Colman. AA Quantitative Metabolic Defect in Lipid Metabolism Associated with Abnormal Serum Lipoproteins in Man.@Circulation. Vol. 7, March 1953, pp. 393B402.  "

LBL-60. Blood Volume Studies Using Dextran and Phosphorus-32BLabeled Red Blood Cells

DURING THE EARLY 1950s, researchers at the Donner Laboratory, University of California Radiation Laboratory, Berkeley and Highland Alameda County Hospital, Oakland conducted studies on blood volume following administration of dextran (a plasma substitute) using phosphorus-32 (P³²)Blabeled red blood cells.

The subject pool for this study consisted of 24 patients with chronic lymphocytic leukemia, 17 patients with chronic myelogenous leukemia, and 10 males with fractures (one of whom had liver cirrhosis). The latter 10 patients were administered dextran. Three patients who served as controls received only saline. Each subject (aside from the three controls) underwent two blood volume measurements using an established technique that included labeling 5 milliliters of blood drawn from the subject with 500 microcuries of P³² and reinjecting 1 milliliter.

The results of these studies showed an increase in blood volume among the 10 subjects administered dextran. The three control patients showed no significant change in blood volume. This work was supported by the U.S. Atomic Energy Commission.

References

Berlin, N.I., J.H. Lawrence, and J. Gartland. AThe Blood Volume in Chronic Leukemia as Determined by P³²-Labeled Red Blood Cells.@Journal of Laboratory and Clinical Medicine. Vol. 36, 1950, pp. 435B439.

Meyer, L.M., N.I. Berlin, G.M. Hyde, R.J. Parson, and B. Whittington. AChanges in Blood Volume Following Administration of DextranCDetermined by P³²-Labeled Red Cells.@Surgery Gynecology and Obstetrics. Vol. 94, 1952, pp. 712B714.  "

LBL-61. Measurement of Blood Volume Using Chromium-51

DURING THE EARLY 1950s, researchers in the Department of Radiology, University of California Medical School, San Francisco with others in the Radioisotope Unit, Veterans Administration Hospital at Fort Miley, made measurements of blood volume using chromium-51 (Cr⁵¹). The purpose of this study was to determine if the anemia observed in cancer patients is due to excessive red blood-cell destruction, or to increased plasma volume. One hundred seventy-five hospitalized patients with various types of cancer and 87 normal individuals participated as subjects.

A sample of blood was drawn from each subject, labeled with Cr⁵¹, and reinjected intravenously. After 1 hour, another blood sample was drawn and activity was measured to determine blood volume, plasma volume, and red cell mass.

The studies showed that patients with nonmetastatic cancers exhibited lower-than-normal whole-blood volumes. Patients with all types of cancer, except colon cancer, had lower red cell masses and higher plasma volumes than normal. Patients with leukemia or cancer of the stomach, esophagus, or colon had higher than normal blood volumes. This work was supported by the U.S. Atomic Energy Commission.

References

Reilly, W.A., H.L. Helwig, and K.G. Scott. ABlood-Volume Measurements in Cancer Using the Cr⁵¹ Red Blood Cell Tagging Method.@Cancer. Vol. 9, MarchBApril 1956, pp. 273B276.  "

LBL-62. Body Composition Studies Using Tritium

IN THE EARLY 1950s AND 1960s, researchers at the Donner Laboratory, University of California Radiation Laboratory, Berkeley and the Division of Medical Physics, University of California, Berkeley conducted a series of studies on the fat, water, blood, and bone volumes in the human body. The procedure to determine a total water volume routinely made use of oral or injected tritium (H³)-labeled water as a tracer.

The total-body water and body composition of 100 normal subjects, ages 20 to 80, was evaluated using tritium. The experiment was designed to determine the deviations in body composition in various body types, from lean to obese.

The results indicated not only wide variations in body compositions from lean to obese subjects, but also wide variation in groups of subjects with similar densities or body water. This work was supported by the U.S. Atomic Energy Commission.

References

Berlin, N.I., and W.E. Siri. AIsotopic Determination of Body Composition in Man.@Progress in Atomic Medicine. 1965, pp. 34B53.

Siri, W. AFat, Water, and Lean Tissue Studies.@In Federation Proceedings of the American Physiological Society. Vol. 12, March 1953, p. 133.

Siri, W. AThe Gross Composition of the Body.@In Advances in Biological and Medical Physics, edited by J. Lawrence and C. Tobias, pp. 239B280. Vol. 4, 1956.  "

LBL-63. Blood Studies in Congestive Heart Failure Using Phosphorus-32 and Sodium-24

IN 1950, researchers at the Donner Laboratory, University of California Radiation Laboratory, Berkeley conducted tracer studies using phosphorus-32 (P³²) and sodium-24 (Na²⁴) to determine total red cell volume, plasma volume, and sodium space in patients with congestive heart failure. This research was conducted to better understand the physiological processes involved.

Twenty-seven male and female patients at the Highland Alameda County Hospital, ranging in age from 34 to 84 years, were used as subjects. Blood, red cell, and plasma volumes were determined using established techniques. Five milliliters of blood samples from each subject were labeled with 500 microcuries of P³² and 1 milliliter of the labeled sample was reinjected into the subject. Exchangeable body sodium was determined by administering 100 microcuries of Na²⁴ and then measuring the radioactivity in a plasma sample taken 18 hours after injection.

The study showed that 12 patients had normal blood, red cell, and plasma volumes. Fifteen patients had either an elevated blood volume, total red cell volume, or plasma volume. This work was supported by the U.S. Atomic Energy Commission.

References

Prentice, T.C., N.I. Berlin, G.M. Hyde, R.J. Parsons, J.H. Lawrence, and S. Port. ATotal Red Cell Volume, Plasma Volume, and Sodium Space in Congestive Heart Failure.@Journal of Clinical Investigation. Vol. 30, 1951, pp. 1,471B1,482.  "

LBL-64. Experimental Cancer Therapy Using Gold-198, Yttrium-90, and Chromium-51

FROM 1950 TO 1955, cancer patients with ascites (cancer-caused fluid in the abdominal cavity) and pleural effusions (fluid in the chest cavity) were treated at the Donner Laboratory, University of California Radiation Laboratory, Berkeley and at the Alta Bates Hospital using gold-198 (Au¹⁹⁸) or yttrium-90 (Y⁹⁰).

Sixteen female patients ranging in age from 34 to 62 years were administered 23 to 120 millicuries of Au¹⁹⁸ or Y⁹⁰ by injection into the affected body cavity. Small samples of fluid were removed after 24 hours to assess the activity of the isotope remaining in the cavity. Two patients received injections in the chest and abdomen and one patient underwent three separate abdominal injections. Follow-up consisted of observation for the return of ascitic fluid. One patient was also administered 0.5 millicurie of chromium-51 (Cr⁵¹). This material was deemed unsatisfactory, and the patient then was administered 61 millicuries of Y⁹⁰.

Of the 20 total treatments to the 16 patients, 11 were observed to render the patient free of ascites for a period of time. The Donner Laboratory was supported by the U.S. Atomic Energy Commission.

References

Lawrence, John H. Summary of Gold Treatment at Donner Laboratory/Summary Gold TreatmentCAlta Bates Hospital Series. Berkeley, CA: Lawrence Berkeley Laboratory, Individual Personnel Case Files, Radiation Biology & DNA Repair, Accession 434-91-0156, File Code 1-1-14, Carton 1 of 3, Folder 18.  "

LBL-65. Study of Local Blood Flow in Bone Marrow in Patients with Leukemia and Neoplastic Diseases Using Iodine-131

BETWEEN 1951 AND 1952, researchers at the Laboratory of Experimental Oncology, University of California, San Francisco; the National Cancer Institute; and the Division of Medicine and Cancer Research, University of California Medical School, San Francisco conducted studies on blood flow in human bone marrow using iodine-131 (I¹³¹) as a tracer. The purpose of the studies was to determine the relative rates of clearance of I¹³¹ from the bone marrow, to ascertain the blood flow in human bone marrow, and to obtain information on the clearance rates from the gastrocnemius muscle.

A total of 44 patients, with various neoplastic diseases, lymphoblastomas, and leukemia participated as subjects. The subjects were 31 males ranging in age from 9 to 79 years, and 13 females between 5 and 63 years of age. Ten to 30 microcuries of I¹³¹ were injected into the marrow tissue of each patient. Most patients also received intramuscular injections of 10 to 30 microcuries of I¹³¹. Activity was externally counted for 15 to 30 minutes following injection.

The results of these studies showed a selective increase in blood flow in the bone marrow in acute leukemia and in some cases of chronic lymphocytic leukemia and multiple myeloma. The studies also suggested that fundamental differences in the marrow vascular bed exist among the leukemic group of diseases. Use of I¹³¹ to evaluate blood flow in bone marrow was considered a research tool in studying cancer patients and applied over time, at least into the 1960s. The University of California Medical School, San Francisco received funding from the U.S. Atomic Energy Commission (AEC) through a contractual arrangement, and intermittently shared facilities and personnel with the AEC-funded predecessors to Lawrence Berkeley Laboratory.

References

Petrakis, N.L., S.P. Masouredis, and P. Miller. AThe Local Blood Flow in Human Bone Marrow in Leukemia and Neoplastic Diseases as Determined by the Clearance Rate of Radioiodide (I¹³¹).@Journal of Clinical Investigation. Vol. 32, 1953, pp. 952B963.

Scott, K.G. Radioactivity Research Center Report. San Francisco: University of California at San Francisco, 1962B63. Special Collections Library, School of MedicineCDean Papers, Accession AR 90-56, Carton 6, Folder AOrganized Research Radiology Laboratory.@ "

LBL-66 Localization of Deep-Seated Tumors Using Potassium-42

FROM 1954 THROUGH 1956, researchers at the University of California Medical School, San Francisco studied the effectiveness of potassium-42 (K⁴²) as an agent for localizing deep-seated tumors. The purpose of this study was to find better means of localizing deep tumors and to determine metabolic activity in tumor tissue.

Thirty-three patients were administered K⁴² to localize and identify deep-seated tumors by surface measurement methods. A scintillation counter with a collimator was used to localize tumors, which were presumed to have a high metabolism of potassium.

Available information indicates that the results of these studies were inconclusive. This work was supported by the U.S. Atomic Energy Commission.

References

Project Summary. AThe Use of K⁴² as an Indicator for the Localization of Deep-seated Tumors.@Edwin B. Boldrey, M.D. Papers. University of California at San Francisco. Special Collections Library. Accession Number MSS 88-56, Carton 1, Folder S.

Letter. E.B. Boldrey to R.S. Stone. January 30, 1956. Boldrey, Edwin Barkley M.D. Papers. University of California at San Francisco. Special Collections Library. Accession Number MSS 88-56, Carton 1, Folder S.  "

LBL-67. Measurement of Residual Fluid in the Fasting Stomach Using Zirconium-95/Niobium-95 as Tracer

DURING THE MID-1950s, researchers at the Department of Medicine and the Radioactivity Research Center, University of California Medical School, San Francisco measured the rate of gastric fluid secretion and amounts of gastric fluid remaining in empty stomachs. These measurements were made using zirconium-95/ niobium-95 (Zr⁹⁵/Nb⁹⁵) complex as a tracer. Thirty-six patients, none with clinical evidence of gastric retention, participated as subjects. Each was administered 0.5 microcurie of Zr⁹⁵/Nb⁹⁵, mixed with a quantity of water and a chelating agent (versene or EDTA). Within 1 minute, samples were drawn from the stomach and activity was measured to determine the amount of dilution.

The study showed that the gastric volume remaining after aspiration varied uniformly from 3 to 83 milliliters. Seventy-five percent of the participants had a residual volume of 20 milliliters or more. The University of California Medical School, San Francisco received funding from the U.S. Atomic Energy Commission (AEC) through a contractual arrangement, and intermittently shared facilities and personnel with the AEC-funded predecessors to Lawrence Berkeley Laboratory.

References

Liebowitz, D., H.H. Stone, D. LeVine, K.G. Scott, and T.L. Althausen. ARadioactive Dilution Indicator: Measurement of Residual Fluid in the Fasting Stomach.@Gastroenterology. Vol. 32, No. 2, February 1957, pp. 265B267.  "

LBL-68. Measurement of Sodium-24 Movement in Normal Subjects

DURING THE MID-1950s, researchers at the Donner Laboratory, University of California Radiation Laboratory, Berkeley conducted studies on the movement of sodium in the human body using sodium-24 (Na²⁴). The purpose of the studies was to correlate the early movement of sodium with age and gender to determine the relationship between blood circulation and aging.

Study subjects included 63 healthy male and 70 healthy female volunteers ranging in age from 22 to 90 years. Each subject was intravenously administered 30 to 50 microcuries Na²⁴ as chloride (Na²⁴Cl). Movement of the radioisotope was measured for 35 to 120 minutes.

These studies showed that the sodium mixing rate slowed with increasing age, and that the mixing rate was generally higher among women than among men. This work was supported by the National Heart Institute, the National Institutes of Health, and the U.S. Atomic Energy Commission

References

Strajman, E., H.B. Jones, P.J. Elmlinger, J.W. Gofman, and G.E. Ward. ARelationship of Age and Sex to Early Mixing of Na²⁴ in Normal Man.@Journal of Applied Physiology. Vol. 8, No. 5, March 1956, pp. 540B555.  "

LBL-69. Aspirin Absorption Studies Using Carbon-14

DURING THE MID-1950s, researchers at the Donner Laboratory, University of California Radiation Laboratory, Berkeley conducted studies to determine and compare the absorption levels of two different aspirin products using an unstated amount of carbon-14 (C¹⁴) as a tracer. Seven study subjects ingested aspirin that had been labeled with C¹⁴. Measurement of exhaled C¹⁴ dioxide (C¹⁴O₂) indicated the absorption rate of the aspirin.

The results of these studies indicated no difference in the absorption rate of the two products. The Donner Laboratory was supported by the U.S. Atomic Energy Commission.

References

AThe Henry B. Freiberg Memorial Lecture.@BioMed Donner Lab Scientists=Papers, Dr. John Lawrence, 1940B1985. LBL Accession 434-94-0016, File Code 19-4-6, Folder AFreiberg Lecture.@

Letter. H.G. Parker to M.L. Painter. October 14, 1958. Dr. Howard G. Parker Research & Development Files. LBL Accession 434-94, File Code 19-14-153, Carton 112, Folder AHG ParkerCPersonal.@  "

LBL-70. Studies on Protein-Bound Iodine­131 in Children

DURING THE MID-1950s, researchers at the Departments of Pediatrics and Radiology, University of California Medical School, San Francisco; the San Francisco Veterans Administration Hospital; and the San Francisco Children=s Hospital conducted studies to measure protein-bound iodine in human plasma.

Fourteen children ranging in age from 4 to 14 years with poliomyelitis, but normal thyroid function, participated as subjects. Each received oral doses of 10 to 30 microcuries of iodine-131 (I¹³¹) as a tracer. Blood samples were drawn at intervals and the plasma was treated with anionic resin. Samples were counted to determine the amount of plasma protein-bound iodine.

When compared with data from another study involving 27 euthyroid (normal thyroid) adults, this study showed that children appear to release protein-bound iodine earlier, and in greater amounts, than adults. The University of California Medical School, San Francisco, received funding from the U.S. Atomic Energy Commission (AEC) through a contractual arrangement, and intermittently shared facilities and personnel with the AEC-funded predecessors to Lawrence Berkeley Laboratory.

References

Reilly, W.A., K.G. Scott, R.W. Winters, and H.L. Helwig. AAnionic Resin Measurement of Protein-Bound I¹³¹ in Euthyroid Children.@American Medical Association Journal of Diseases in Children. Vol. 89, 1955, pp. 572B574.  "

LBL-71. Studies of Red Blood-Cell Production in Patients with Polycythemia Vera Using Iron-59 and Phosphorus-32

DURING THE 1950s AND EARLY 1960s, researchers at the Donner Laboratory, University of California Radiation Laboratory, Berkeley conducted studies on red blood-cell production using iron-59 (Fe⁵⁹). The purpose of these studies was to classify the patterns of red cell production in patients with polycythemia vera (a chronic disease characterized by an abnormal increase in red blood-cell production) to aid in diagnosis of the disease.

Sixty-four patients ranging in age from 6 to 78 years participated as subjects. For each subject, plasma was obtained from a blood sample and mixed with 10 to 40 microcuries of Fe⁵⁹. Five to 20 milliliters of this solution were then injected into the same donor. Blood samples were then drawn over the next 14 days and analyzed for plasma and red cell radioactivity. Surface measurements over the liver, spleen, and sacral bone marrow were also obtained to determine Fe⁵⁹ activities in these organs. Plasma and red cell volumes were determined, independently, by conventional methods involving the administration of Fe⁵⁹ and phosphorus-32 (P³²). Seven of the patients participated in repeat studies over a 12-year period. The clinical course and pathologic findings at postmortem examination (autopsy) on the patients were correlated with the previous study data.

The results of these studies provided data for classifying the diagnosis of polycythemia vera according to red cell activity and for determining appropriate therapy. This work was supported by the U.S. Atomic Energy Commission.

References

Pollycove, M., H.S. Winchell, and J.H. Lawrence. AClassification and Evolution of Patterns of Erythropoiesis in Polycythemia Vera as Studied by Iron Kinetics.@Berkeley, CA: University of California Lawrence Radiation Laboratory, UCRL-16246, Spring 1965.

Pollycove, M., H.S. Winchell, and J.H. Lawrence. AClassification and Evolution of Patterns of Erythropoiesis in Polycythemia Vera as Studied by Iron Kinetics.@Blood: The Journal of Hematology. Vol. 28, No. 6, December 1966, pp. 807B829.  "

LBL-72. Experimental Treatment of Cancer with Heavy Charged Particles

FROM THE MID-1950s THROUGH THE MID-1970s the Lawrence Berkeley Laboratory=s 184-inch synchrocyclotron was used to create heavy particle beams for use in experimental treatment and clinical trials of cancer therapy. Early experiments included three cases of patient brain tumor irradiation in 1961 and 1962. Subsequent cases utilizing the Bragg peak of the 910-MeV (million electron volt) alpha-particle beam for treatment included at least six patients with brain tumors, three patients with pulmonary metastases, two patients with Parkinson=s disease, and one case of acromegaly with large hypophyseal tumor. The maximum doses to the tumors in these cases ranged from 2,500 to 6,000 rads.

In the early 1970s, Donner Laboratory researchers began preparations for what would become the clinical trials of the program of cancer treatment with heavy charged particles. The tumors considered for treatment with heavy nitrogen and heavy neon beams in this phase included craniopharyngioma, pinealoma, brain-stem tumor and glioblastoma multiforme, esophageal carcinoma, advanced carcinoma of the cervix, osteogenic sarcoma, Ewing=s tumor, soft-tissue sarcomas and synoviomas (especially of childhood), chordomas and malignant tumors of the vertebral bodies, parotid and middle ear tumors, chest wall lesions, breast cancer, and carcinoma of the prostate. The total dose to the tumor site was between 5,000 and 7,000 rads.

Clinical trials in the mid-1970s were concerned with the establishment of a protocol and the study of technical matters such as dosimetry for the helium-ion beam and other heavy-ion therapies that were eventually used. The program at this point was supported by the U.S. Energy Research and Development Administration and by a grant from the National Cancer Institute.

References

Gottschalk, A., J.T. Lyman, and L.W. McDonald. Use of the Bragg Peak for Brain-Tumor Therapy. Berkeley, CA: Lawrence Berkeley Laboratory. Donner Laboratory Scientists=Papers, Dr. John Lawrence, 1940B1985. Accession 434-92-0066, File Code 19-14-6, Carton 3 of 18, Folder ALung Meta Brain Tumors.@

Tobias, C.A. Documents relative to treatment of cancer with helium and heavy ions, 1977B1978.Berkeley, CA: Lawrence Berkeley Laboratory. Group R&D Administrative Files (C.A. Tobias), Radiation Biophysics Group Proposal Files 1973B1986. Accession 434-92-0338. File Code 19-10-20, Carton 2, Folder 18, ABMD-38.@

Manuscript. J.H. Lawrence. Brain Tumors (labeled AExcerptCItaly Chapter@). Berkeley, CA: Lawrence Berkeley Laboratory. Biomed Donner Laboratory Scientists=Papers, Dr. John Lawrence, 1940B1985. Accession 434-92-0066, File Code 19-14-6, Carton 3 of 18, Folder ALung Meta Brain Tumors.@

Letters. J.H. Lawrence to V. Collins. May 17, 1971 and September 29, 1971. J.H. Lawrence to R.L. Clark. March 28, 1972. The Bancroft Library. John H. Lawrence Correspondence. BANC MSS87/86c. Carton 7. Folder AC Correspondence 1971B72.@

Letters. J.H. Lawrence to W.E. Powers, September 29, 1971, May 26, 1972 and July 3, 1972. J.H. Lawrence to W.M. Preston. May 3, 1971. W.E. Powers to J.H. Lawrence. June 5, 1972. The Bancroft Library. John H. Lawrence Correspondence. BANC MSS 87/86c. Carton 7, Folder APi-Q Correspondence 1970B1973.@

Letters. J.H. Lawrence to Drs. Chong, Garcia, Hollander, Landaw, Linfoot, Manougian, McRae, Okerlund, Van Dyke, and Winchell. October 8, 1971. The Bancroft Library. John H. Lawrence Correspondence. BANC MSS87/86c, Carton 7, Folder AD Correspondence 1971B73.@

Letters. J.H. Lawrence to Drs. S.D. Bloom and H. Barschall, November 22, 1971. J.H. Lawrence to N.I. Berlin. February 24, 1972. The Bancroft Library. John H. Lawrence Correspondence. BANC MSS87/86c. Carton 7. Folder ABa-Bl Correspondence 1970B73.@

Letter. C.Y. Chong to J.H. Lawrence and J.G. Archambeau. March 13, 1972. The Bancroft Library. John H. Lawrence Correspondence. BANC MSS87/86c. Carton 7. Folder AA Correspondence 1971B72.@  "

LBL-73. Studies of Human Growth and Development Involving the Use of Tritium, Sodium-24, and Iodine-131 as Tracers

FROM 1954 THROUGH THE EARLY 1970s, researchers at the Donner Laboratory, University of California Radiation Laboratory, Berkeley conducted studies of human growth and development in collaboration with several departments on the Berkeley campus, including the Institute of Human Development, the School of Optometry, the Department of Physiology-Anatomy, Medical Physics and Nutritional Sciences, and the Colwell Memorial Hospital. The researchers studied individuals who had been subjects in a series of earlier studies of the physical, physiological, and psychological aspects of childhood and adolescent growth that were initiated at Berkeley in the late 1920s and early 1930s.

The Donner Laboratory studies involved the 120 traceable participants among the Oakland Growth Study group, that in 1932 comprised about 200 male and females, who were members of the fifth grades at five schools in Oakland. This subgroup, all members in their thirties, participated in a comprehensive series of medical examinations that included about 100 different measures of physical status, body composition, urine and blood chemistries, renal and circulatory systems function, basal metabolism, respiration, and sensory functions. Some of these tests involved the use of iodine-131 (I¹³¹), tritium (H³), and sodium-24 (Na²⁴) as tracers of the biological processes. The amounts of activity administered to each subject were not provided in the supporting documents. However, early test material mixtures contained about 0.17 millicurie of I¹³¹, 2.0 millicuries of H³, and 12.0 microcuries of Na²⁴ together in 50 milliliters of water.

These studies yielded valuable information about changes in physiological measurements associated with growth, development, and the aging process. This work was funded by the U.S. Public Health Service. The Donner Laboratory was supported by the U.S. Atomic Energy Commission.

References

Jones, Harold E. AThe Oakland Growth Study: Fourth Decade.@Newsletter of the Gerontological Society. Vol. 5, No. 1, 1958.

Letter and attached funding application. J.H. Lawrence to J. McDaniel, Jr., December 2, 1955. University of California, The Bancroft Library. Hardin Jones Correspondence & Papers, Banc Mss 79/112c, Box 6, Folder ALawrence, John Hundale.@

Letter. R.D. Tuddenham to H.B. Jones. December 27, 1968. University of California, The Bancroft Library. Hardin Jones Correspondence & Papers, Banc Mss 79/112c, Box 11, Folder AT Miscellaneous.@

Letter and attached grant application. P.S. Timiras to H.B. Jones. September 3, 1969. University of California, The Bancroft Library. Hardin Jones Correspondence & Papers, Banc Mss 79/112c, Box 11, Folder ATimiras, Paola Silvestri.@ "

LBL-74. Study of the Effects of Altitude on Red Cell Production and Volume Using Tritium, Phosphorus-32, and Iron-59

FROM SEPTEMBER 6 TO OCTOBER 10, 1957, researchers from Donner Laboratory, University of California Radiation Laboratory, Berkeley conducted blood studies in Bolivia using phosphorus-32 (P³²) and iron-59 (Fe⁵⁹). The purpose of the studies was to examine red cell production and volume at high altitudes. Four volunteer medical students and four Indian miners participated as subjects.

A series of tests were administered to the students in La Paz, Bolivia, and later repeated at a mountain laboratory at 17,000 feet of elevation. The same tests were administered to the miners, who had lived at an elevation of about 17,000 feet for about 4 years. Phosphorus-32 was administered in a blood volume test and Fe⁵⁹ was administered in tests of plasma turnover, plasma volume, and red cell uptake. Tritium (H³) was also administered in a total-body water test.

Preliminary study results showed that red cell volume has a slight tendency to increase at higher elevations, that plasma volumes remain the same, and that plasma turnover increases at higher altitudes. This work was supported by the U.S. Public Health Service and the U.S. Atomic Energy Commission, in cooperation with the University Mayor de San Andres, the High Altitude Cosmic Ray Laboratory, and the General and Labor Hospitals of La Paz, Bolivia.

References

Siri, W.E., and C. Webster. Report on Studies Conducted in Bolivia by Donner Laboratory. Berkeley, CA: Lawrence Berkeley National Laboratory, Administration Division, Lawrence Berkeley Laboratory Business Manager Research and Development Administrative Files, 1946B1957. Lawrence Berkeley Laboratory Accession 434-90-0020, File Code 13-11-14, Carton 26/26, Folder AReport-Donner Lab-Bolivian Project.@ "

LBL-75. Estimates of Lean-Body Weight and Skeletal Size Using Tritium and X­Rays

DURING THE PERIOD from 1958 to 1959, scientists at the U.S. Naval Radiological Defense Laboratory, San Francisco and at the Donner Laboratory, University of California Radiation Laboratory, Berkeley collaborated in a study of lean-body weight and skeletal size in humans. The purpose of this study was to determine reference values for normal, healthy individuals. Thirty-one healthy Navy personnel served as subjects for a study of lean-body weight, total-body water, and skeletal size.

Total-body water was determined by the tritium space method using water labeled with an unreported amount of tritium (H³) that was taken orally. Samples of urine were collected and analyzed for tritium activity. Using standard techniques, x­ray radiographs were taken of 22 of the same healthy subjects to determine the sizes of various skeletal structures, including the size of arm, leg, chest, and pelvis bones. The gonads received only negligible exposures, being outside the primary x­ray beam. The Donner Laboratory was supported by the U.S. Atomic Energy Commission.

References

Behnke, A. AThe Estimation of Lean Body Weight From >Skeletal=Measurements.@Human Biology. Vol. 31, No. 4, December 1959, pp. 296B316.  "

LBL-76. A Study of the Effectiveness of Silver-111 as a Tracer in Liver Functions Tests

IN APPROXIMATELY 1959, researchers from the San Francisco Veterans Administration Hospital and the University of California Medical School, San Francisco studied the human metabolism of radiosilver using silver-111 (Ag¹¹¹). The purpose of these studies was to determine if radioactive silver might be used as a tracer to measure liver function. The 24 study subjects included cirrhotic patients and patients with normal liver function. Ten to 30 microcuries of Ag¹¹¹ were incubated with plasma obtained from each subject and were injected intravenously.

The results of the study showed that Ag¹¹¹ was removed from the plasma principally by the liver, with the rate of removal being less in the cirrhotic subject than in the normals. Following maximal uptake, the clearance half-time of Ag¹¹¹ in normal subjects was about 11 days, compared to 20 days in cirrhotic subjects. Seven of the patients involved in the study were considered terminally ill at the time of administration of the silver and subsequent autopsy specimens showed that the largest proportion of Ag¹¹¹ in the body was deposited in the liver. One subject who had received radiosilver 8 days before death had 99.6 percent of the remaining radioactivity in the liver.

The study also showed that radiosilver was not a promising tracer for liver function assays (tests) due to the difficulty of its preparation and its long retention in the liver. The University of California Medical School, San Francisco received funding from the U.S. Atomic Energy Commission (AEC) through a contractual arrangement, and intermittently shared facilities and personnel with the AEC-funded predecessors to Lawrence Berkeley Laboratory.

References

Reilly, W.A., K.G. Scott, and G.L. Searles. AThe Clearance of Ag¹¹¹ from Plasma and Liver of Cirrhotic and Non-Cirrhotic Patients.@Journal of Nuclear Medicine. Vol. 1, No. 191, July 1960, pp. 191B194.  "

LBL-77. Iodine Uptake Studies in Thyroid Cancer Patients Using Iodine-131

DURING THE EARLY 1960s, researchers at the San Francisco and Berkeley campuses of the University of California conducted metabolic studies using iodine-131 (I¹³¹) as tracers. Forty-three cancer patients at the Fort Miley Veterans Administration Hospital participated as subjects.

The studies showed that in some cancer patients, I¹³¹ remained in the bloodstream or concentrated in tumors and other tissues, rather than accumulate in the thyroid gland as expected. This phenomenon was described as Aiodine trapping.@This work was supported by the American Cancer Society and the University of California, San Francisco. The University of California Medical School, San Francisco, received funding from the U.S. Atomic Energy Commission (AEC) through a contractual arrangement, and intermittently shared facilities and personnel with the AEC-funded predecessors to Lawrence Berkeley Laboratory.

References

Scott, K.G. Listing of Slides. Berkeley, CA: University of California at Berkeley, Bancroft Library, BANC 80/81, Box 1, Folder AD.H. Papers.@

President Kerr=s Report to the Regents. Berkeley, CA: University of California at Berkeley, June 23, 1961. Bancroft Library, BANC 80/81, Box 1, Folder AMiscellaneous.@

Memorandum. R. Papac to W.M. Silliphant. April 19, 1960. University of California at Berkeley, Bancroft Library, Hardin B. Jones: Committees, Speeches, Reprints, Papers, BANC 79/112c, Box 1, Folder AUCB Cancer Board Meetings, MayBJune, 1960.@ "

LBL-78. Studies on Iron Loss Using Iron­59

DURING THE EARLY 1960s, researchers at the Donner Laboratory, University of California Radiation Laboratory, Berkeley conducted studies on daily total-body iron loss using iron-59 (Fe⁵⁹) as a tracer.

Twelve normal males ranging in age from 19 to 43 years participated as subjects. Two subjects received intravenous administration of 18 microcuries of Fe⁵⁹ that had been incubated with plasma. Ten subjects received injections of 5 microcuries of Fe⁵⁹ that had not been incubated with plasma. Activity was measured over the next 300 days by whole-body counting and by analysis of urine and stool samples.

These studies showed that the average daily iron loss rate was 0.03 percent, and that the whole-body counter was an accurate, simple means of measuring iron loss. This work was supported by the U.S. Atomic Energy Commission.

References

Saito, H., T. Sargent, H.G. Parker, and J.H. Lawrence. Whole-Body Iron Loss in Normal Man, Measured with a Gamma Spectrometer. Berkeley: Berkeley, CA: University of California Lawrence Radiation Laboratory, UCRL-11387, Spring, 1964.  "

LBL-79. Blood Volume Studies in Healthy Humans Using Chromium-51 as Tracer

DURING THE EARLY 1960s, scientists at the University of California Medical School, San Francisco conducted blood volume studies using chromium-51 (Cr⁵¹) as tracer. The purpose of these studies was to collect data to develop standards for predicting normal values of red cell mass and plasma volumes, and to derive an equation that related blood volumes with height and weight. The subjects for this study were 17 healthy males, 101 healthy females, and 201 healthy male prison inmates.

Fifteen milliliters of each subject=s blood were drawn and labeled with 50 to 200 microcuries of radioactiveCr⁵¹ as sodium chromate. Ten milliliters of the labeled blood were returned by intravenous administration to each subject. Blood samples were drawn within 35 minutes of administration for Cr⁵¹ analysis. Regression equations were derived, and from those equations, blood volume and red blood-cell volumes for males and females were estimated.

The results showed that females had a higher red cell volume and a lower plasma volume than males of comparable height and weight. The results also showed that age, physical habits, and muscularity had little influence on blood volume. This work was supported by the U.S. Public Health Service, American Heart Association, the Robert Harris Fund, and the James Edwards Memorial Fund. The University of California Medical School, San Francisco received funding from the U.S. Atomic Energy Commission (AEC) through a contractual arrangement, and intermittently shared facilities and personnel with the AEC-funded predecessors to Lawrence Berkeley Laboratory.

References

Berlin, N.I., G.M. Hyde, R.J. Parsons, and J.H. Lawrence. ABlood Volume in Various Medical and Surgical Conditions.@New England Journal of Medicine. 1952, Vol. 247, pp. 675B684.

Brown, E., J. Hopper, Jr., J.L. Hodges, Jr., B. Bradley, R. Wennesland, and H. Yamauchi. ARed Cell Plasma and Blood Volume in Healthy Women Measured by Radiochromium Cell­Labeling and Hematocrit.@Journal of Clinical Investigation. Vol. 41, 1962, pp. 2,182B2,190.

Reilly, W.A., French, R.M., Lau, F.Y.K., K.G. Scott, and W.E. White. AWhole Blood Volume Determined by Radiochromium-Tagged Red Cells: Comparative Studies on Normal and Congestive Heart Failure Patients.@Circulation. Vol. 9, 1954, pp. 571B580.

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.

Wennesland, R., E. Brown, J. Hopper, Jr., J.L. Hodges, Jr., O.E. Guttentag, K.G. Scott, I.N. Tucker, and B. Bradley. ARed Cell, Plasma, and Blood Volume in Healthy Men Measured by Radiochromium (Cr⁵¹) Cell Tagging and Hematocrit: Influence of Age, Somatype, and Habits of Physical Activity of the Variance after Regression of Volumes to Height and Weight Combined.@Journal of Clinical Investigation. Vol. 38, 1959, pp. 1,065-1,077.

Wennesland, R., E. Brown, J. Hopper, Jr., K.G. Scott, J.L. Hodges, Jr., and B. Bradley. AExperiences with the Radiochromium Method for Determination of Red Cell Volume.@Scandinavian Journal of Clinical and Laboratory Investigation. Vol. 14, 1962, pp. 355B367.

Yamauchi, H., E.G. Biglieri, and J. Hopper, Jr. ABlood Volume and Aldosterone Secretion in Hypertension and Primary Aldosteronism.@In Proceedings of the Society of Experimental Biology and Medicine. Vol. 107, 1962, pp. 728B731.  "

LBL-80. Studies of Blood Flow to Bone Using Fluorine-18

DURING THE EARLY 1960s, researchers at the Donner Laboratory, University of California Radiation Laboratory, Berkeley conducted studies on blood flow to bone using fluorine-18 (F¹⁸). The purpose of the studies was to correlate F¹⁸ distribution with skeletal growth rate and various disease states. One 19-year-old female with a leg fracture and four patients with Paget=s bone disease participated as subjects.

Two hundred microcuries of F¹⁸ were administered intravenously to each subject, and the resulting activity in bone was assayed using a positron gamma camera.

The studies showed that distribution of F¹⁸ administered intravenously was uneven in normal skeletons, and was markedly altered in pathological conditions. Furthermore, F¹⁸ accumulated at fracture sites, tumor sites, and in the lesions of Paget=s disease; a finding attributed to increased numbers of blood vessels (vascularity) in these areas. This work was supported in part by the U.S. Atomic Energy Commission.

References

Van Dyke, D., H.O. Anger, Y. Yano, and C. Bozzini. ABone Blood Flow Shown with F¹⁸ and the Positron Camera.@American Journal of Physiology. Vol. 209, JulyBDecember 1965, pp. 65B70.

Letter. D. Van Dyke to H.B. Jones. March 29, 1968. University of California, The Bancroft Library. Hardin Jones Correspondence & Papers, Banc Mss 79/112c. Box 11. Folder: AVan Dyke, Donald.@  "

LBL-81. Blood Volume Studies Using Chromium-51 and Iodine-131 in Diagnosis of Aldosteronism

IN 1961, researchers at the University of California Department of Medicine; the Cardiovascular Research Institute; the Radioactivity Research Center; and the University of California Department of Statistics, San Francisco and Berkeley conducted blood volume studies to improve the diagnosis of hypertension and aldosteronism (a disorder caused by excessive secretion of the hormone aldosterone). An improved method for measuring total blood volume was tested on about 201 healthy male and 101 healthy female volunteers.

Samples of each subject=s blood were labeled with 50 to 75 microcuries of Cr⁵¹ as sodium chromate, and reinjected. Samples of circulating blood were then counted for Cr⁵¹ activity. This method was applied as part of a study of hypertension and primary aldosteronism involving two hospital patients with aldosteronism and five patients with hypertension. Plasma volumes were also determined using iodine-131Blabeled human serum albumin to allow calculation of true whole blood volume and body hematocrit (the percentage of the volume of a blood sample occupied by red cells).

The results showed that primary aldosteronism could be diagnosed by observing an increase in plasma volume with normal hematocrit. These studies were supported by the U.S. Public Health Service, the American Heart Association, and the Committee on Research of the University of California Medical School. The Radioactivity Research Center at the University of California Medical School, San Francisco was supported by the U.S. Atomic Energy Commission.

References

Wennesland, R., Brown, E., Hopper, J., Scott, K. G., J. L. Hodges, and B. Bradley. AExperiences with Radiochromium Method for Determination of Red Cell Volume.@Scandinavian Journal of Clinical and Laboratory Investigation.Vol. 14, 1962, pp. 355B367.

Yamauchi, H., E. G. Biglieri, and J. Hopper, Jr. ABlood Volume and Aldosterone Secretion in Hypertension and Primary Aldosteronism.@InProceedings of the Society of Experimental Biology and Medicine. Vol. 107, 1962, pp. 728B731.  "

LBL-82. Experimental Therapy for Leukemia Using Yttrium-90

IN JUNE OR JULY OF 1961, physicians at the Donner Laboratory, University of California Radiation Laboratory, Berkeley administered yttrium-90 (Y⁹⁰) to a 3-year-old child for treatment of acute leukemia. This resulted in an estimated 200 rads of internal radiation to the lymphatic tissue. The purpose of this effort was to treat acute leukemia with a form of Y⁹⁰ that was thought to concentrate in lymphatic tissues.

The therapy resulted in a temporary remission with complete disappearance of all abnormal lymphocytes from the peripheral blood and bone marrow, and with little effect on the granulocytes or red cells. The Donner Laboratory was supported by the U.S. Atomic Energy Commission.

References

Speech. J.H. Lawrence, AIsotopes and Nuclear Radiations in Medicine or A Quarter Century of Nuclear Medicine.@Evening lecture delivered at the International Conference on the Use of Radioisotopes in Animal Biology and the Medical Sciences, sponsored by the International Atomic Energy Agency, the Food and Agriculture Organization of the United Nations and the World Health Organization, Mexico City, November 24, 1961. Biology and Medicine, Scientists Papers, Dr. John Lawrence, 1932B1984, Accession 434-92-0277, File Code 19-14-6, Carton 3/6, Folder ASpeeches-JHL.@

Paper. S. Winchell, M. Pollycove, A.C. Andersen, and J.H. Lawrence. ASelective Beta Irradiation of the Lymphatic System of the Dog Using Y⁹⁰-DTPA: Kinetics, Dosimetry, and Biologic Evaluation.@Presented at the Meeting of the American Society for Clinical Research, Carmel, CA, January 1962.  "

LBL-83. Studies of Fatty Acid Metabolism Using Palmitic Acid Labeled with Carbon-14 as a Tracer

BETWEEN 1961 AND 1963, researchers at the University of California Medical School, San Francisco conducted metabolic studies using palmitic acid labeled with carbon-14 (C¹⁴) as a tracer. The purpose of these studies was to examine the relationship between free fatty acids in the plasma and triglyceride fatty acids.

Two male subjects, ages 48 and 56 years, were intravenously injected with approximately 100 microcuries of palmitic acid labeled with C¹⁴ complexed to human serum albumin. Serial blood samples were drawn over the following 72 hours to measure C¹⁴ activity. This study showed that free fatty acids in the plasma are the major precursors of triglyceride fatty acids.

Palmitic acid labeled with C¹⁴ was used in two similar studies with different test subjects. Between January 1, 1962, and June 30, 1963, palmitic acid labeled with C¹⁴ was intravenously injected into young diabetic subjects hospitalized in the metabolism ward of Moffitt Hospital. In another study, a group of subjects over 40 years old received constant intravenous infusions of C¹⁴-labeled palmitic acid during exercise.

This work was supported by the U.S. Public Health Service, the American Heart Association, and the Monterey and Napa Valley Heart Associations. The University of California Medical School, San Francisco received funding from the U.S. Atomic Energy Commission (AEC) through a contractual arrangement, and intermittently shared facilities and personnel with the AEC-funded predecessors to Lawrence Berkeley Laboratory.

References

Havel, R.J. AConversion of Plasma Free Fatty Acids into Triglycerides of Plasma Lipoprotein Fractions in Man.@Metabolism Clinical and Experimental. Vol. 10, No. 12, December 1961, pp. 1,031B1,034.

Radioactivity Research Center Report. San Francisco: University of California at San Francisco, School of Medicine, January 1, 1962 to June 30, 1963. Dean, Papers. AR90-56. Carton 6 of 13. Folder AOrganized Research Radiology Lab 1962/63.@Special Collections, The Library, University of California, San Francisco.  "

LBL-84. Bone Marrow Distribution of Iron Using Iron-59 and Iron-52 as Tracers

IN 1963, researchers at Donner Laboratory, University of California Radiation Laboratory, Berkeley conducted studies on bone marrow distribution using iron-59 (Fe⁵⁹) and iron-52 (Fe⁵²). The purpose of the studies was to evaluate methods for determining total marrow in the skeleton.

Three adult malesCone normal control and two anemic patientsCparticipated as subjects. Each received an intravenous injection of 40 microcuries of Fe⁵⁹. Distribution within the marrow was measured by whole-body scanning. One subject was administered an unstated amount of Fe⁵² to measure marrow distribution in selected areas of the body.

The results of these studies showed considerable peripheral extension of bone marrow after prolonged, massive stimulation. Increases in red cell production up to 13 times normal could be achieved without any great marrow extension. This work was supported in part by the U.S. Atomic Energy Commission.

References

Van Dyke, D., H. Anger, and M. Pollycove. AThe Effect of Erythropoietic Stimulation on Marrow Distribution in Man, Rabbit, and Rat as Shown by Fe⁵⁹ and Fe⁵².@Blood: The Journal of Hematology. Vol. 24, No. 4, October 1964, pp. 356B371.  "

LBL-85. Physiological Studies on Mount Everest Climbers Using Iron-59 and Tritium

IN 1963, researchers at the Donner Laboratory, University of California Radiation Laboratory, Berkeley conducted high-altitude physiological studies using iron-59 (Fe⁵⁹) and tritium (H³). Members of the 1963 American Mount Everest Expedition, including 17 healthy males ranging in age from 24 to 44 years, participated as subjects.

Plasma iron turnover rate, plasma volume, and red cell volume measurements were made by drawing a sample of blood, labeling it with Fe⁵⁹, and reinjecting it into the subject. Total body water was measured by orally administering tritium and analyzing the activity in subsequently collected urine samples. Studies were conducted both at the Donner Laboratory and in the field at various altitudes.

The studies showed increased plasma iron turnover rates and higher red cell volumes at high altitudes and a rapid decrease in red cell volume upon return to sea level. This work was supported by the U.S. Air Force Office of Scientific Research and the U.S. Atomic Energy Commission.

References

Siri, W.E. Final Report of Physiological Studies on Mt. Everest Climbers. Berkeley, CA: University of California, The Bancroft Library, June 1965. William Siri Mt. Everest Expedition Files, BANC MSS 88/22c, Carton 1, Folder APhysiological Studies on Mt. Everest Climbers.@

Siri, W.E., D.C. Van Dyke, H.S. Winchell, M. Pollycove, H.G. Parker and A.S. Cleveland. AEarly Erythropoietin, Blood, and Physiological Responses to Severe Hypoxia in Man.@Journal of Applied Physiology. Vol. 21, JanuaryBNovember 1966, pp. 73B80.  "

LBL-86. Tumor Localization Studies Using Selenium-75, Mercury-197, Technetium-99m, and Strontium-85

IN THE MID-1960s, researchers at the Radioisotope Service; Veterans Administration Hospital; and the Radioactivity Research Center, University of California Medical School, San Francisco conducted brain scanning studies using selenium-75 (Se⁷⁵) in collaboration with the San Francisco Veterans Administration Hospital. The purpose of these studies was to determine whether radioactive selenium would improve diagnostic accuracy in scanning for brain and bone tumors. Fifty-two patients with intracranial disease and 25 patients with focal bone lesions participated as subjects.

Four microcuries of Se⁷⁵ as sodium selenite per kilogram of body weight were administered intravenously to each subject, and scans were accomplished 1 to 6 days following injection. Preliminary brain scans were performed with either mercury-197 (Hg¹⁹⁷), 10 microcuries per kilogram of body weight, or technetium-99m (Tc^99m), 100 microcuries per kilogram of body weight. Routine bone scans also were made after administration of 10 microcuries of strontium-85 (Sr⁸⁵).

The results of these studies showed that Se⁷⁵ was superior to Sr⁸⁵, Tc^99m, or Hg¹⁹⁷ in differentiating between brain tumors and vascular lesions, and superior also in differentiating bone tumors from non-neoplastic lesions. Because of its relatively long half-life (45 days), Se⁷⁵ was recommended as a secondary scanning agent. The Radioactivity Research Center at the University of California Medical School, San Francisco was supported by the U.S. Atomic Energy Commission.

References

Cavalieri, R.R., and K.G. Scott. ASodium Selenite Se⁷⁵: A More Specific Agent for Scanning Tumors.@Journal of the American Medical Association. Vol. 206, No. 3, October 14, 1968, pp. 591B595.  "

LBL-87. Iron Kinetics Studies Using Iron­59

DURING THE LATE 1960s, researchers at the Donner Laboratory, University of California Radiation Laboratory, Berkeley conducted studies of erythropoiesis (red blood-cell formation and turnover) and developed new methods for investigating heme (the oxygen-carrying component of hemoglobin) synthesis and degradation in healthy and diseased subjects. The purpose of this work was to develop a simplified means of obtaining clinical information about heme synthesis, mean red-cell turnover time, and rates of iron storage exchange.

Two or more hospital patients, including a 9-year-old boy with cystic fibrosis and an enlarged spleen, participated as subjects. Each was intravenously administered plasma that had been labeled with 2 to 5 microcuries of iron-59 (Fe⁵⁹) as ferrous citrate. Plasma samples were obtained at 10,15, 20, 30, 45, 60, and 90 minutes following the injection to determine plasma iron-turnover rate. Whole-body scans were obtained the day after injection and again 2 weeks after injection. Plasma iron-turnover rate was determined by a blood sample at the time of the second scan. The Donner Laboratory was supported by the U.S. Atomic Energy Commission.

References

Winchell, H.S., and S.A. Landaw. Letter to the Editor: AIron Kinetics and Whole-Body Scanning of Iron Using Less Than 5:Ci of Fe⁵⁹.@Journal of Nuclear Medicine. Volume 11, No. 4, pp. 180B181.

Letter. H.S. Winchell to H.B. Jones. March 28, 1968. The Bancroft Library. Hardin Jones Correspondence & Papers. BANC MSS79/112c. Box 11. Folder AW Miscellaneous.@

Application. S.A. Landaw, ARevision and Supplement to Research Career Program Application.@U.S. Public Health Service Research Career Program Application No. 1-K4-HE-17, 693-01A1, April 1969; January 5, 1970. The Bancroft Library. John Hundale Lawrence Correspondence. BANC MSS87/86c. Carton 7. Folder AD Correspondence 1971-1973.@ "

LBL-88. Experimental Tumor Imaging Using Gallium-67

DURING THE LATE 1960s, researchers at the Donner Laboratory, University of California Radiation Laboratory, Berkeley in collaboration with the Oak Ridge Associated Universities, conducted studies on tumor imaging using gallium-67 (Ga⁶⁷). The purpose of these studies was to evaluate the effectiveness of Ga⁶⁷ as a tumor-visualizing agent using the Anger whole-body camera, scintillation camera, and tomographic scanner. Eighteen patients, nine men and nine women with established diagnoses of malignant tumors, participated as subjects.

Approximately 4 millicuries of Ga⁶⁷ citrate were administered to each subject by intravenous injection. In addition, one patient was administered an unspecified amount of technetium-99m for comparison of image quality using this radionuclide. Patient imaging took place over the next 6 days using cameras at various settings.

The results of these studies showed that Ga⁶⁷ was useful in clinically evaluating the presence and distribution of malignant neoplastic tissue in humans. This work was supported by the U.S. Atomic Energy Commission.

References

Winchell, H.S., P.D. Sanchez, C.K. Watanabe, L. Hollander, H.O. Anger, J. McRae, R.L. Hayes, and C. Edwards. AVisualization of Tumors in Humans using Ga⁶⁷-Citrate and the Anger Whole-Body Scanner, Scintillation Camera and Tomographic Scanner.@Journal of Nuclear Medicine. Vol. 11, No. 7, 1970, pp. 459B466.  "

LBL-89. Study of Metabolic Abnormalities in Asparagine-Dependent Tumors Using Carbon 14

DURING THE LATE 1960s, researchers at the Donner Laboratory, University of California Radiation Laboratory, Berkeley used UL-L-asparagine (an amino acid) labeled with carbon-14 (C¹⁴) to demonstrate and assess abnormalities in asparagine metabolism in L-asparagineBdependent tumors. The purpose of this study was to develop a method of assessing the effectiveness of treatment of this type of tumor.

Two female patients with advanced L-asparagineBdependent tumors, a nonwhite 19-year-old and a white 54-year-old, participated as subjects. They had malignant lymphatic tumors with primary bone involvement and multiple myeloma with widespread involvement of bone and organs, including the kidneys or stomach, respectively.

Each subject received 5 to 10 microcuries of C¹⁴-UL-L-asparagine by intravenous injection, followed several weeks later by chemotherapy specific to their disease. Carbon-14 excretion, as measured by C¹⁴ activity in expired carbon dioxide (C¹⁴O₂), was determined for each subject both before and after administration of the chemotherapy.

The percent of C¹⁴O₂ excreted per minute was increased in both C¹⁴-asparagine treated subjects after chemotherapy compared with the pre-chemotherapy values. The researchers concluded the C¹⁴O₂ measurement method may be useful in assessing the effectiveness of treatment of this type of tumor and that it might form a basis for studying metabolic abnormalities associated with various neoplastic processes. This work was supported by the James Picker Foundation and the U.S. Atomic Energy Commission.

References

Chaudhuri, T.K., and H.S. Winchell. ADiminished Oxidation of C¹⁴-UL-L-Asparagine to C¹⁴O₂ in Mice and Humans with Tumors: A Possible Means for Assessing Efficacy of Therapy?@Journal of Nuclear Medicine. Vol. 11, No. 10, 1970, pp. 597B601.  "

LBL-90. Carbon-14 Bicarbonate Kinetics in Adult Males

AROUND 1969, researchers at the Donner Laboratory, University of California Radiation Laboratory, Berkeley conducted studies on normal bicarbonate-CO₂ excretion kinetics in resting and exercising humans.

In one study, 1.4 to 6.3 microcuries of sodium bicarbonate labeled with carbon-14 (C¹⁴) as tracer were administered intravenously to 13 normal male subjects at rest, breathing normally into a breath-analysis apparatus. The C¹⁴O₂ and total CO₂ excretion in the breath were monitored continuously in each subject for a minimum of 2 hours following injection.

In a related study, five of the same subjects were studied at rest and during physical exertion on an exercise bicycle. Before the administration of the C¹⁴-bicarbonate, bicycle exercising was continued for a sufficient time to ensure that oxygen consumption and CO₂ production had reached a steady state. Two microcuries of C¹⁴-labeled sodium bicarbonate were then injected intravenously; and the subject=s C¹⁴O₂ excretion was studied while the subject continued a constant level of exercise over the ensuing 2-hour period.

These studies showed that exertion of a limited group of muscles resulted in a selective increase in blood flow to these muscles without alteration of the absolute blood flow rate to unexercised muscles. This work was supported by the U.S. Atomic Energy Commission.

References

Slanger, B.H., N. Kusubov, and H.S. Winchell. AEffects of Exercise on Human CO₂-HCO₃ Kinetics.@Journal of Nuclear Medicine. Vol. 11, No. 12, 1970, pp. 716B718.

Winchell, H.S., H. Stahelin, N. Kusubov, B. Slanger, M. Fish, M. Pollycove, and J.H. Lawrence. AKinetics of CO₂-HCO₃ in Normal Adult Males.@Journal of Nuclear Medicine. Vol. 11, No. 12, 1970, pp. 711B715.

Letter. B. Slanger to J. Born. August 25, 1969. Lawrence Berkeley Laboratory. Biology & Medicine R&D Administrative Files, Accession 434-90-0209, File Code 16-5-22, Carton 1, Folder ABlood Reimbursement Approvals.@  "

LBL-91. Study of Methionine Metabolism in Folic-AcidBDeficient and Vitamin B₁₂-Deficient Patients Using Carbon-14

IN 1969, RESEARCHERS at the Donner Laboratory, University of California Radiation Laboratory, Berkeley conducted studies on metabolic abnormalities associated with deficiencies of B₁₂ and folic acid, using carbon-14 (C¹⁴) as a tracer.

Four patients were intravenously administered 11 to 15 microcuries of L-histidine (an amino acid) labeled with C¹⁴. They then ingested various amounts of L-methionine (also an amino acid) prior to another administration of the labeled L-histidine. Their breath was analyzed for the presence of carbon dioxide labeled with C¹⁴.

The results of the studies failed to show any effect of ingestion of L-methionine on the production of carbon dioxide labeled with C¹⁴ resulting from the administered L-histidine. This, in turn, failed to confirm in humans the results of previous animal studies. This research was supported by the U.S. Atomic Energy Commission.

References

Stahelin, H.B., H.S. Winchell, and N. Kusubov. ALack of Effect of L-Methionine Ingestion on C¹⁴O₂ Excretion from L-Histidine (Imidazole-2-C¹⁴) in Folic Acid and Vitamin B₁₂ Deficient Humans.@Blood: The Journal of Hematology. Vol. 35, No. 1, January 1970, pp. 86B89.  "

LBL-92. Visual Perception Studies Using Neutron Beams

IN THE EARLY 1970s, researchers at the Donner Laboratory, University of California Radiation Laboratory, Berkeley and the University of Washington Department of Radiology, Seattle conducted studies on the effects of neutron beam exposure on vision. The purpose of these studies was to duplicate and determine the cause of brilliant flashes and streaks reported by astronauts during space flights. Berkeley scientists had observed this effect as early as 1952.

In a 1976 follow-up experiment, six subjects were exposed to neutrons produced by the University of Washington=s cyclotron. Each subject received a total dose of approximately 200 millirads during a 100-second exposure. All reported seeing colorless Astars@and Astreaks,@with intensity proportional to the energy level of the exposure.

In another study at the University of California at Berkeley three scientists were exposed to high-energy neutron beams produced at the Bevatron accelerator. All reported a variety of visual sensations in response to different experimental protocols.

The results of these studies suggested that the visual phenomenon experienced by astronauts was caused by interaction between the retina and alpha particles produced by neutron radiation encountered during space flight. This research was supported by the National Aeronautics and Space Administration and the U.S. Atomic Energy Commission.

References

Budinger, T.F., H. Bichsel, and C.A. Tobias. AVisual Phenomena Noted by Human Subjects on Exposure to Neutrons of Energies Less than 25 Million Electron Volts.@Science. Vol. 172, May 21, 1971, pp. 868B870.

Budinger, T.F., J.T. Lyman, and C.A. Tobias. AVisual Perception of Accelerated Nitrogen Nuclei Interacting with the Human Retina.@Nature. Vol. 239, No. 5369, September 22, 1972, pp. 209B

Tobias, C.A., C.T. Gaffey, M.J. Malachowski, and T.C. Yang. AEffects of Heavy Ions on the Neuron System with Special Reference to Vision.@Annual Progress Report. Berkeley, CA: Lawrence Berkeley National Laboratory, NASA P.O. T7163B, December 1976. Division of Biology and Medicine, Lawrence Berkekely Laboratory, Berkeley, California.  "

LBL-93. Nutritional Studies Using Carbon-14 as Tracer

IN 1971, RESEARCHERS at the Donner Laboratory, University of California Radiation Laboratory, Berkeley collaborated in nutritional studies using carbon-14 (C¹⁴) as a tracer for serum glycerides in lipoproteins. The purpose of the study was to assess serum glyceride turnover rate during a period of acute weight loss to improve the understanding of lipoprotein metabolism and its role in obesity in humans. Eight obese but otherwise healthy females participated as subjects.

As part of a controlled, 63-day weight loss program, each subject was intravenously administered approximately 10 microcuries of glycerol labeled with C¹⁴. Blood samples were obtained at specific time intervals and analyzed for C¹⁴ activity to determine glyceride turnover rate.

This study showed that glyceride turnover rate was higher for obese women than for normal-weight women. There was no significant change in turnover rate during periods of significant weight loss. This research was supported in part by the U.S. Atomic Energy Commission.

References

Jourdan, M., S. Margen, and R.B. Bradfield. AThe Turnover Rate of Serum Glycerides in the Lipoproteins of Fasting Obese Women During Weight Loss.@The American Journal of Clinical Nutrition. Vol. 27, August 1974, pp. 850B858.

Letter. H.B. Jones to C.W. Koch. July 16, 1971. The Bancroft Library. Hardin Jones Correspondence and Papers. BANC MSS 79/112c. Box 13. Folder ALetters written by Jones, JulyBDecember 1970.@

Letter. H.B. Jones to A. Grendon. July 1971. The Bancroft Library. Hardin Jones Correspondence and Papers. BANC MSS 79/112c. Box 13. Folder: ALetters written by Jones, July B December 1970.@

Letter. C.W. Koch to H. Jones. July 12, 1971. The Bancroft Library. Hardin Jones Correspondence and Papers. BANC MSS 79/112c, Box 6, Folder AKoch, Charles William.@  "