Attachment 4 August 9, 1949 A. Graham Moseley, Jr., M.D. Asst. Chief, Radioisotope Section Research and Education Service Department of Medicine and Surgery Veterans Administration Washington, 25, D.C. Dear Dr. Moseley: Thanks very much for sending me the "proceedings" of the March 17-18 meeting of the Radioisotope Unit representatives in Chicago. We are very pleased to note that another meeting and a tentative date of October 6 has been set, with the selection of Los Angeles as the place. All of us will be very glad to have suggestions of the obligations and responsibilities of our group in making this meeting a success. There is a good deal of material here which can be given and which I am sure will be of interest to those attending. I cannot make much of a recommendation for a local program at this moment because Drs. Laiby, Dowdy and others are away on vacation and expect to be back by the end of August. I am likewise leaving for a brief two weeks at the end of this week, but if you will send on anything that you wish to have done, we will get at it in Washington as to what our possibilities are. With very best wishes, I remain Cordially yours, Stafford L. Warren, M.D. SLW:jh Dean, School of Medicine cc: Dr. Andrew Dowdy Dr. E.V. Edwards ILLEGIBLE metastases of thyroid cancer. With enthusiastic support of the Chiefs of Surgery and Pathology, Dr. Hagelstein has been preforming tracer studies and radioautographic studies of all thyroid tissues and nodules removed in operation. The results will be of considerable assistance in evaluation the functional status of thyroid nodules and indicating the advisability of therapy with I131 Use of radioiron to label erythrocytes and determine their maximum age has shown that in patients with ILLEGIBLE nocturnal ILLEGIBLE newly formed erythrocytes behave quite differently from older erythrocytes, and also, quite differently from newly formed erythrocytes in normal individuals. The results of this study were real by title at the meeting of the American Society of Clinical Investigation at Atlantic City, May 2, 1949. Studies of erythrocyte fragility by this technique are continuing. WORK CONTEMPLATED DURING THE CURRENT YEAR: a. Therapy. We will continue to treat leukemia and polycythemia with p32. It is our belief that this treatment of choice in most cases of chronic myelogenous leukemia and lymphocytic leukemia, and in case but not all cases of polycythemia vera. Use of I131 will be continued in selected cases of Graves Disease and in cases of thyroid carcinoma in which the neoplastic cells show assimilation of I131. We propose to us Au198 in treatment of advanced neoplasms if the Surgical Service can be interested in such treatment. b. Diagnosis. We will cooperate with Dr. Silverstone in the use of p32 in Localization and demarcation of neoplastic processed in the central nervous system. The use of I131 in the study of thyroid abnormalities will be increased. This will involve quantitative evaluation of the pickup of I131 by the thyroid, quantitative assay of urinary ILLEGIBLE of tracer doses, and surveys of various regions of the body for evidence of metastatic thyroid malignancy. Radioautographic techniques will be used in evaluating the functional nature of thyroid adenomas and neoplasms. c. Research. The use of p32 to tag erythrocytes will be employed in the study of blood volumes of patients with cardiac diseases, nephrosis and various types of hematologic abnormalities. The techniques will also be used to evaluate blood volumes of patients subjected to radical surgical procedures. We propose to develop the radioautographic technique from a technical standpoint and employ it with the morphology of the thyroid gland. Studies are being initiated of the distribution of radioiron between the blood and various tissues. This will involve tracer loses of radioiron to patients with neoplastic disease with quantitative tissue analyses for radioiron in the foreseeable future. 2. Unit for such determinations, when hyperthyroidism was suspected. These patients required a total of 700-individual tracer studies, in addition to 560-individual invitro examinations of excretions. Tracing of aberrant thyroid tissue has been performed in several cases referred by medical and surgical services. Detection of metastatic thyroid carcinoma was undertaken in 13-patients. The Neurological Service has joined in the employment of radioactive radiofluorescein for the pre-operative diagnosis of brain tumors, in six cases. A special field of interest has been the use of radiophosphorus in diagnosis of malignant tumors of the testicle. A total of 15-patients with suspected malignant tumors of the testicle were traced preoperatively. A paper presenting the results of this work has been accepted by the Journal of Urology. Summary of Therapy and Diagnosis Carried Out No. Patients Therapy Diagnosis No. Patients 126 27 No. doses 182 46 No. in-vivo studies 936 134 No. in-vitro studies 708 176 c. Research. Animal and human studies are in progress employing red blood cells labeled with p32 to determine blood volumes. In cooperation with the Dermatology Section preliminary studies are under way employing the application of radiophosphorus to superficial benign and malignant skin lesions. Four patients with multiple lesions are under treatment. Accurate determination of erythema values is of special interest. Complete and extended follow-up of thyroid gland uptake and excretion of radioiodine in suspected cases of hyperthyroidism is expected to yield valuable data of prognostic significance. Preliminary studies of this kind are under way and will be reported in the literature. WORK CONTEMPLATED FOR THE COMING YEAR: a. Therapy. Radioiodine will be employed in a larger number of cases of hyperthyroidism, and the prognostic use of extensive follow-up data will be evaluated. Studies will be undertaken on the complex problems attending the treatment of metastatic thyroid carcinomas, ILLEGIBLE efforts made to increase the uptake of radioiodine by such agents as propylthiouracil and thyroid stimulating hormone. The management of chronic leukemia and malignant lymphomas with radiophosphorus will be ILLEGIBLE and ILLEGIBLE of dosage by various methods attempted. b. Diagnosis. Hyperthyroidism will be our major interest. Simulating conditions such as anxiety neurosis, cardiac states, neurocirculatory asthma, etc. will be carefully studied in large groups. c. Research. The possibilities of radiophosphorus as a diagnostic and prognostic tool in a variety of malignant tumors will be the subject of special attention. Modification of radioiodine dosage for management. 5 ABSTRACT OF PROGRESS REPORT FORT HOWARD Authorized September 14, 1948, with Dr. John E. Dovers as Director PHYSICAL FACILITIES: A separate brick building has been assigned to the Unit. A construction project for alternations and fined equipment for this building has been approved after a long delay, and the project is now in progress. The finished building will contain a large central laboratory, an instrument room, a clinical laboratory, storage and preparation room, small animal room and office totaling about 3000-square feet. One-half of a former gymnasium has also been assigned and is in use for storage and assembly of equipment and will be used for classroom purposes. Equipment procurement has been carried out satisfactorily and time has been spent on calibration and assembly of instruments. PERSONNEL: In addition to the Director, who serves as a Consultant basis, personnel consists of a biochemist, a physicist, an instrument technician and a biological aid. All of these have been successfully employed under Civil Service. Papers are being processed for an M.D. with extensive research experience who will join the Unit shortly. WORK IN PROGRESS: There have been no clinical applications of radioisotopes as yet. Much time has been ILLEGIBLE in standardizing techniques for the preparation, use, recovery, and measurement of radioiodine and radiophosphorus. Other results are represented by progress in procurement of supplies and equipment assembly of equipment, planning and calibration. WORK CONTEMPLATED FOR THE COMING YEAR: a. Therapy. Radiophosphorus will be used in the treatment of appropriate doses of chronic myeloid leukemia, chronic lymphoid leukemia, multiple myeloma, and polycythemia vera. Radioiodine will be used for therapy of thyroid carcinoma and selected masses of hyperthyroidism - ILLEGIBLE those with complicating heart disease or evidence of recurrent nerve or parathyroid injury 7 b. Diagnosis. Studies on red cell volume by the Surgical Service, using radiophosphorus. Radioactive sodium will be used in studies on ILLEGIBLE circulation in occlusive arterial disease and in studies on volume competency. Radioiodine will be used in thyroid studies and for ILLEGIBLE proteins for studies on plasma volume. c. Research. The major field of interest is in studies of endocrine and metabolic system in health and disease. For example radioiodine will be used as a tool for study of abnormal thyroid relationships by following its uptake after administration of ILLEGIBLE. Compound C, ILLEGIBLE ILLEGIBLE and Neo-epinephrine. We would also like to study the effects on ILLEGIBLE and radioiodine uptake. ILLEGIBLE will be used to study the effect of varying concentrations of iodine in the medium on the development of the thyroid gland. We would like also to determine if those ILLEGIBLE which decrease the sensitivity of normal tissue to radiation will similarly affect neoplastic tissue. SPECIAL ACTIVITIES: An educational program was instituted soon after the activation of the Unit. Discussions were held, for the staff of the hospital and others, on effects of radiation, toxicity of radio-isotopes, use of radioiodine and other radioisotopes, and on instrumentation and methods of measurement. The University of Maryland has suggested that it would like to assign resident physicians to the Unit for three months rotation. Future plans are for a training activity in this Unit. This would allow assignment of Veterans Administration personnel for varying periods of in-service training in radioisotope technique. Some work has been carried out in the direction of teaching courses of varying type for this purpose. ************************ 8 ABSTRACT OF PROGRESS REPORT CLEVELAND Period of September 1948 to September 1949; Dr. Maurice Sachs, Director PHYSICAL FACILITIES: The Unit moved from temporary quarters to the newly equipped laboratory of approximately 2,200-square feet in January 1949. The new space consist of ten rooms as follows: Biochemistry Laboratory, High Level Laboratory, Low Level Laboratory, Repair Room, Counting Room, Auxiliary Counting Room, Dark Room, Storage Room, two Offices. These laboratories are completely equipped with adequate furniture, except that a hood is needed in one laboratory and some additional work benches and storage cabinets should be added to the Biochemistry Laboratory. Satisfactory equipment has been installed, calibrated and is in use. PERSONNEL: Personnel added during the year include a Chemist, two Chemistry Technicians and a Physical Science Aid. Total personnel now total 8, in addition to the Director. Only one technician is under Civil Service, all other personnel being employed as Consultants per Annum. One additional technician will be requested during the year. WORK COMPLETED AND IN PROGRESS: a. Therapy. The major therapeutic use has been treatment of diffuse toxic gaiter with I131. More recently we have undertaken the treatment of leukemia with p32. b. Diagnosis. The major diagnostic application has been the study of all types of thyroid cases with I131. Total patients receiving ILLEGIBLE doses of I131, either at VA or ILLEGIBLE Hospitals, number 65, involving 30-doses. Seven patients undergoing thyroidectomy at VA Hospital have had tracer doses of I131, with three receiving treatment with I131 for recurrent hyperthyroidism following thyroidectomy. c. Research. Blood volumes studies have been performed for 30-patients conILLEGIBLE with Western Reserve University, under the guidance of Fr. Friedell and with the support of Dr. Shuamy. Localization of brain tumors with I131 labelled diiodofluorescein has been attempted but the study has not progressed enough to warrant conclusions. A study on the labeling of human serum albumin with radioiodine, and the technical problems attendant thereto has been initiated. Attempts to impregnate silver with large amounts of radioiodine have been only partially successful. Work toward the development of a scintillation counter has not been successful as yet. 9 A few radioautographic of thyroid tissues may have been made, but until recently the number of surgical thyroid doses available for study was small. The occasional administration of thorium ILLEGIBLE has offered us opportunities to study its radiation dosage and this has been done when possible. WORK CONTEMPLATED FOR THE COMING YEAR: a. Therapy. Alternate cases of diffuse tonic gaiter will be treated with radioiodine and surgery, It is anticipated that cases of myelogamous leukemia and polycythemia will be treated with p32. b. Diagnosis. Studies of various thyroid abnormalities will be continued with I131. Such cases as may be available will be used in attempts to localize brain tumors with labelled diiodofluorescein. c. Research. It is anticipated that a satisfactory maximum yield of iodinated albumin will be obtained. The attachment of radioiodine to metallic silver will be further investigated. A major program will be the investigation of changes in blood volume cases of malnutrition, anesthesia, the Smithwick procedure and polycythemia. Dr. Hayman hopes that we may be able to investigate the utilization of iron by nephritic patients, using radioiron tracer methods. An effort will be made to acquire as much information as possible on patients not known to have thyroid disease. Use of radioiodine in patients receiving anti-thyroid drugs will be a basis for attempting to determine the interval in which such drugs take effect. SPECIAL ACTIVITIES: At present patients are being treated in the Metabolism Ward, which may not be available indefinitely. It is hoped that additional space may become available to provide a histological laboratory, additional office space, and a clinical laboratory for GM accounting of patients with stationary equipment over extended periods of time. Dr. Manov of the Bureau of Standards visited the Unit in November 1948 and assisted in formalizing our radioassay procedures. Open house on the post was held in January 1949 to acquaint the personnel of the hospital with the Unit and its purpose. Interdepartmental Conferences were held in February 1949 for determining policy on thyroid cases, and in July 1949 for determining policy on thyroid cases, and in July 1949 for discussion of a program for determining blood volumes in cases of acute gastrointestinal hemorrhages. Mr. Gray delivered talks to the Physiotherapy Department and to the Nursing Department. Mr. Kromer talked to the Unit personnel on precautions and safety. 10 ABSTRACT OF PROGRESS REPORT HINES Period of September 1948 to September 1949; Dr. George V. LeRoy, Director PHYSICAL FACILITIES: During the year additional space has been assigned and equipped from Section funds, without a construction project application. Total floor space for the Unit is approximately 1,600-square feet. This including a microcurie laboratory, a millicurie laboratory, instrument room, radiophysisc laboratory, treatment room, and office. All except the office are air conditioned. The laboratories have stainless steel benches and excellent fluorescent lighting. Equipment procurement has proceeded rapidly and is satisfactory. PERSONNEL: Dr. LeRoy accepted appointment to a full-time position as Director effective July 28, 1949. Mr. Theodore Fields was appointed as Radioisotope Scientist (Physics) in February and has been actively working toward improvement of instrumentation and related problems. Other personnel include Dr. Tweedy, Associate Director; Miss Zorn, Biochemist; two technicians; a biological aide; a secretary; and a nurse for the radioisotope treatment center. WORK COMPLETED AND IN PROGRESS: a. Therapy. A total of 24-patients with blood dvscrasias has been treated with p32. I131 has been used in treatment of 12-cases of hyperthyroidism and 7-cases of thyroid carcinoma. Au198 has been used in two cases for interstitial radiation of neoplasms. b. Diagnosis. Studies using I131 have been made on 150- patients, with the routine study including uptake-excretion measurement and determination of precipitable protein; bound I131. Studies on space-filling intra-cranial lesions, using diiodofluorescein, have been made on 54-patients. c. Research. The study of parathyroid function continues and we are now able to determine as little as 1.0 USO units of parathyroid hormone. The study of technical methods for utilizing I131 for thyroid studies in general hospitals continues. WORK CONTEMPLATED FOR THE COMING YEAR: a. Therapy. Development of technique of therapy with colloidal Au198 and other colloidal compounds of radioelements. 11 b. Diagnosis. Equipment is being prepared on measure blood volume, cardiac output and cardiac function time factors. c. Research. Continuation of the studies currently in process. A systematic study of thyroid function. A study of parathyroid function in selected patients. A study if radioautography of tumors. SPECIAL ACTIVITIES: Informal training in radioisotope techniques has been given to two residents in neurosurgery and one member of the University of Illinois faculty. A more formalized program of training is being studied. A formal two weeks training program for nurses has been drafted and will be undertaken this fall. A great deal of time and effort has been devoted to fundamental studies of the application of tracer mechoiology to clinical problems. These include: a. Technique for precipitable protein-bound iodine. b. Makeup studies of the geometry involved in estimations of I131 uptake by the thyroid. New arrangements will decrease the standard error from 25% to less than 8%. Better tubes (Sylvania) will increase counting efficiency by a factor of 10. c. Differential GM counters have been devised for the radiofluorescein study. d. Instrumentation, calibration and radioassay have been studied in great detail with the cooperation of Dr. Jaffrey. We now agree with the NBS p32 within 2%. e. A number of small pilot studies have been made to explore techniques for future use. These include partition of p32 between RBC and ILLEGIBLE: analysis of thyroid tissue removed at surgery, for I131 content: assay with studies relating to National Defense. Dr. LeRoy has been appointed a Consultant to the AEC in connection with studies relating to National Defense. Procurement of radioisotopes in processing packaged and standardized units from Abbott Laboratories has been found to be very satisfactory. 12 ABSTRACT OF PROGRESS REPORT MINNEAPOLIS Period of September 1948 to September 1949; Dr. Howard L. Horns, Director PHYSICAL FACILITIES: During the past year remodeling of the space assigned to the Unit has been completed. However, a serious delay in delivery of laboratory furniture was encountered due to the contract for this furniture being awarded to a firm which has since gone into receivership. Prospects now indicate completion of facilities in the near future. All necessary laboratory equipment has been procured and most instruments have been set up and calibrated. Some are in use for the measurement of radioactivity. PERSONNEL: Dr. Horns had been appointed Assistant Dean of the University of Minnesota Medical School, effective July 1, 1949. This appointment has made it necessary for him to curtail his activities in the Unit. He will continue as Director until a replacement is available. Dr. Leslie ILLEGIBLEieve has been recommended to become Director on January 1, 1950. He already holds a full-time position in the Department of Medicine and Surgery, and has recently attended the course at University of California Medical Center. Other personnel now include a secretary and a physicist (part-time). Dr. Armstrong takes a direct part on a commitment basis. WORK COMPLETED AND IN PROGRESS: A. Therapy. Two cases of hyperthyroidism have been treated with I131. These represent cases in which other therapeutic measures were contra-indicated, according to the current policy of the Medical and Surgical Services. One case of polycythemia rubra vera has been treated with p32. This represents the only suitable case admitted to the Minneapolis hospital. B. Diagnosis. The only case in this ILLEGIBLE was a tumor mass internal to the thyroid whose nature was in question. In this case the I131 uptake was studied. C. Research. A study of the transport of I131 labeled dilILLEGIBLEdofluorescein across the blood-drain barrier is being carried out in cases of surgical brain tumor. This study is incidental to the experimental use of the tagged diiodoflurescein for localization of brain tumors. The suggestion was made that patients completely incapacitated with severe emphysema might benefit from a reduced oxygen requirements 13 secondary to reduced thyroid function. These patients represent impossible surgical risks and as a group are sensitive to many compounds, suggesting I131 as a possible therapy. Studies on six patients with advanced ILLEGIBLE have a deficient uptake of I131 in spite of normal basal rates and histologically normal thyroid glands. WORK COMPLETED DURING THE COMING YEAR: a. Therapy. Expansion of therapy of hyperthyroidism. ILLEGIBLE and treatment of suitable cases of thyroid carcinoma. Continuation of treatment of polycythemia rubra vera by p32. b. Diagnosis. Localization of brain tumors with I131 labeled ILLEGIBLE stain. c. Research. Continuation of projects currently in progress. A comparison of total circulating red cell volume as determined by tracer technique and by the plasma dye-hematocrit method in cases of primary and secondary polycythemia and cases of severe anemia. This comparison is expected to indicate sources of error in the plasma dye-hematocrit method. ************ 14 ABSTRACT OF PROGRESS REPORT DALLAS Period of September 1948 to September 1949; Dr. Julian H. Acker, Director PHYSICAL FACILITIES: The Unit laboratory facilities, housed in a separate building, were completed in the spring of 1949. The laboratories are completely equipped with necessary furniture and fixtures and are air-conditioned. Shop facilities are installed in the same building and have been invaluable in the fabrication of items of special apparatus by Mr. Scaff. Most apparatus has been received and is in use, though a few special items, such as an electrophorese outfit are still in order. PERSONNEL: In addition to the Director, personnel consists of Dr. Henry Lanz, Biophysicist, Mr. William Scaff, Radioactive Scientist (Biology), a secretary and a laboratory helper. All these are under Civil Service in suitable grades. Active consultant assistance on per diem basis is furnished by a bio-chemist, a radiologist, a pathologist and a physicist. During the year it is hoped to obtain a technician and a research assistant trained in chemistry. WORK COMPLETED AND IN PROGRESS: a. Therapy. The clinical program was authorized in March 1949, after adequate development of procedures, standardization and consultant cooperation. Cases of hyperthyroidism, leukemia, polycythemia and psoriasis have been and are being treated by the Unit. b. Diagnosis. Numerous radioiodine uptake studies have been made on cases on suspected thyroid disorders. Radioautograph have been prepared from excised thyroiac of several patients with thyroid ILLEGIBLE. This examined tracer dose of I131 has been 50 micro-curies. NA14 has been used in several cases to determine total ILLEGIBLE cellular fluid volume and for differential circulatory studies in cases pr peripheral vascular disease. p32 has been used in a few cases for determination of blood volume. c. Research. Our major research problem to date has been toward development of a new method of determining cardiac output, using radioactive materials. 15 Diiado Trypan Blue labelled with I131 is being used as the injected substance. Animals will be used until the method is proved suitable and safe. Assistance has been given the ILLEGIBLE Medical Research Program in studies on intravenous administration of oxygen, and the determination of cerebral blood flow. WORK CONTEMPLATED DURING THE COMING YEAR: a. Therapy. The present uses will be continued and expanded to include treatment of thyroid carcinoma. Radiophosphorus will be used in treatment of other types of leukemia and generalized carcinoma cases. b. Diagnosis. To the current program will be added sodium clearance studies us Na32, localization of brain tumors using ILLEGIBLE, and the study of breast tumors with p32. c. Research. The major problem will continue to be the cardiac output study. Other projects planned are: 1. The determination of the inhibitory affect of orally administrated ILLEGIBLE thyroid on the function of normal thyroid glands. 2. Experiments investigating the relationship between the human tubercle bacilli and phospholipid in the phagocytic cells, using p32. 3. Studies to determine the tissue distribution of various radio-elements as a function of the age of the experimental animal. SPECIAL ACTIVITIES The personnel of the Unit have given a series of lectures to the medial staff of the hospital on the medical applications of radioisotopes and the physical fundamentals for the intelligent appraisal of the field. ************ 16 ABSTRACT OF PROGRESS REPORT NASHVILLE Authorized December 23, 1949, with Dr. George R. ILLEGIBLE as Director PHYSICAL FACILITIES: Approximately 4000 sq. ft. of space were allocated to the Unit in the existing hospital. Great progress has been made in equipping this space with work desks and hoods. The desks were fabricated locally from Youngstown steel kitchen units, with special tops covered with linoleum. Stainless steel trays, also fabricated locally, are used in areas of possible contamination. An adequate hood has been constructed. Special items of equipment include Warburg and Tiselius apparatus. PERSONNEL: Personnel in addition to the Director are two biochemist, a physiologist, a biostatistician and a laboratory helper. These are Consultants per Annum except for the helper. An endocrinologist and a biophysicist also visit the Unit once each week on a Consultant basis. WORK IN PROGRESS: a. Therapy. An active program with I131 is in progress in conjunction with surgery. Patients are treated in three categories in this study: 1. Uncomplicated toxic diffuse gaitre -- treated with I131. 2. Uncomplicated toxic modular gaitre -- iodothiourucil followed by subtotal thyroidectomy. 3. Complicated toxic gaitre -- according to clinical judgment with I131, Lugel's, propythicurcil and/or iodothiouracil. Four cases have been managed, two with I131. b. Diagnosis. Thirteen cases of thyroid disease have been studied, with experience resembling published results of others. c. Research. Much time has been spent on instrumentation. This includes construction of certain special instruments as well as extensive calibrations. Iodine standardization is quite unsatisfactory. Arrangements have been made to secure a Bureau of Standards I131 standard. Biochemical research is along two major lines: 1. A study of basic cellular metabolism of the rapidly growing accessory sex organs of the rat. This is under Dr. Rudolph. Testosterone labelled with C14 will be administrated to castrated rats and observations made of activities, radioautograph and Warburg investigation. This is a study 17. of growth and the effect of steroids thereon and constitutes cancer research under the definition of the National Research Council. 2. A study of the effect of anemia and ischemia on heart muscle. This continues the work of Dr . Mensely and associates, and will be primarily the responsibility of Dr. Lamley. C14 and p32 will be used to explore the intimate metabolism of myocardium under anoxic and ischemic insult. Work to date indicated this leads to injury of capillary endothelium, which accounts for irreversible lesions of the heart following temporary ischemia. Physiological Research is primarily the responsibility of Dr. Friedlander. This is along two lines: 1. A study of peripheral circulation using labelled protein, as well as Na24 and p32. Here rapid fixation by freezing of various tissues will be used to determine the relation between intra-and extra-vascular distribution of the injected activity. Biostatistical study of the natural history of polycythemia vera in 30 cases followed at Vanderbilt over 30 years, is being made by Mrs. Ball. This may shed light on the merits of various forms of therapy in this disease, and clarify some of the present confusion regarding the outlook for such patients. WORK COMTEMPLATED FOR THE COMING YEAR: Continuation of the program outlined, which is just getting underway. It is hoped also to develop a colloidal radio-gold therapy program. Arrangements are nearly complete for a clinical peripheral vascular study using p32 and Na24. ************* 18 ABSTRACT OF PROGRESS REPORT VAN NUYS Period of September 1948 to September 1949; Dr. E.M. Morton, Director PHYSICAL FACILITIES: The present laboratory facilities consist of 433- square feet adjacent to the Clinical and Investigate Medical Laboratories. There is also a Radioisotope Ward of nine private rooms. A construction project has been in process for some months for alterations and equipment for 1800 square feet adjacent to the Radioisotope Ward. After much delay the funds for this work have been earmarked, but have not been released to the station pending some further details of work. During the year a circular Barcroft-Warburg apparatus, a Klett Electrophoresis apparatus and a Mass Spectrometer have been received. The Mass Spectrometer has been assembled and is in use. Much of the special remote control devices and shielding equipment has been designed and constructed on the station. PERSONNEL: In addition to the Director, personnel consists of Dr. H.G. Schashrer, four Radioisotope Scientists in low grade levels, two technicians and a secretary. In the ward there are five nurses assigned from general hospital personnel and five ward attendant furnished from Radioisotope Unit funds. One additional technician and one or two scientists in P-1 grade would be described when the new quarters are available. WORK COMPLETED AND IN PROGRESS: a. Therapy. Fifteen cases of hyperthyroidism have been treated with I131. One case of synovisma and two of embryonal carcinoma of the tactes were extensively studied following attempted radioisotope therapy, which was tried after all other forms of therapy had failed and the patients were moribund. I131 as diiodofluorescein Br12 as sodium bromide and Na24 and NaC1 were used. Postmortem tissues are examined chemically and by radioautography. These results will appear as case reports. Two cases of chronic lymphatic leukemia and one of chronic myelogenous leukemia are under treatment with p32. ILLEGIBLE marrow uptake was compared with lymph nodes and blood, and conversion of phosphate into phospholipid was measured. Topically applied p32 has been compared with equivalent soft x-ray dosage in two cases of mycosis ILLEGIBLE. Two cases of this disease are being treated with intravenous p32 as controls. 19. b. Diagnosis. The following studies have been made: 151 studies of thyroid function, which in some cases were repeated as often as 6-times in the same individual. 5 cases with pulmonary lesions suspected of being thyroid metastases. 1 case of metastatic carcinoma of the femur of unknown primary. All cases of nodular thyroid which go to surgery are routinely studied with I131. The lands histology is correlated with function by radioautography and by chemical analysis for radio- iodtyrosine and radiothyroxine. A case report is in preparation describing the metabolism of globulin iodinated with I131 in a patient with hypoglobulinemia and absence of immune bodies as shown by electrophoratic analysis and immologic studies. One case received I131 prior to surgery for carcinoma of the testis, to determine uptake. Autoradiograms were also made. Two cases of Hogkins disease were studied with p32, indicating that lymph modes invaded Hogkins had an uptake of p32 7-6 times as great as bone marrow. C. Research. The mechanisms of thyroxine synthesis and utilization are under investigation in-vitro and in-vivo. Methods of synthesis of radioiodinated thyroxine, diiodithyroxine and diiodothyresine of very high specific activity are under study, in order to study the metabolism of these compounds clinically, in the various states of thyroid function. WORK COMPLETED DURING THE COMING YEAR: a. Therapy. The therapeutic use of radioisotopes will be continued and ILLEGIBLE in the accepted channels. In addition techniques employing colloidal suspensions of radioactive particles even as radiogold, manganese and chronic phosphate will be applied in selected cases of cancer. b. Diagnosis. Diagnostic studies of thyroid function will be continued. Chronic phosphate suspension containing p32 and radioactive dyes is being prepared for use in ILLEGIBLE lymph node localization for radium poisoning will be examined by external beta ray measurements for localization and by expired breath measurements for the quantity of ILLEGIBLE ILLEGIBLE. Diagnostic procedures of peripheral vascular status such as use of Na24 and p32 will be evaluated. c. Research. A clinical program is projected for the study of the metabolism of carbon and nitrogen compound using the mass spectrometer and ILLEGIBLE isotopes. Determination of the rate of disappearance of thyroxine from the circulation will be measured with radiothyroxine, which will require that the patient be exposed to a much smaller amount of radiation than with current radioiodine studies. 20. ABSTRACT OF PROGRESS REPORT LOS ANGELES Period of October 15, 1948 to September 1, 1949; Dr. Raymond L. Libby, Acting Director PHYSICAL FACILITIES: The present laboratory facilities at this Unit consist of 9- rooms as follows: Chemical Laboratory equipped with hood, Immunochemical and Bacteriological Laboratory, Counting Room, Small hot Laboratory, Electron Microscope Laboratory, Dark Room, Machine Shop and office space. These laboratory rooms are completely equipped with the exception of the Dark Room and Machine Shop. Equipment for detection, monitoring research and general laboratory work have been installed, calibrated and in use. Special equipment including Electron Microscope, one Isotope Ratio Mass Spectrometer, one Infra-red Spectrometer and one Visible Spectrometer with ultra violet range attachment are also in use at this Unit. PERSONNEL: Including the Acting Director, personnel at this Unit total seven. All personnel, except the Acting Director, are properly classified Civil Service Employees. Personnel have been organized, trained and are directed to perform in four functions, (1) preparation and source of all radioisotopes used by the staff of the hospital for therapy and diagnosis, (2) provide facilities and personnel on a service basis for various clinical problems and research involving radiotracers, (3) its own research program, (4) a training program designed to familiarize the staff of the hospital with the principles of nuclear physics and with fundamental radioisotope techniques. WORK COMPLETED AND IN PROGRESS: a. Therapy. Therapeutic use of radioisotopes was purposely limited to the use of p32 in two cases of polycythemia ILLEGIBLE and one case of leukemia, awaiting the addition of a qualified M.. to the staff of the Radioisotope laboratory. An M.D. joined the staff on July 10, 1949. It is contemplated that the scope of the therapeutic applications will increase during the next year. b. Diagnosis. The major diagnostic application has been the conducting of ILLEGIBLE-blood volume determinations on cardiac patients using p32. A routine procedure was established after preliminary experiments on p32 uptake by red cells. C. Research. Investigation and preparation of two published reports has been accomplished. The subjects of the reports are "Remote Pipetting, Apparatus for Dispensing Solutions of Radioisotope." and "The Effect of Temperature on the Uptake of Radiophosphorus by the Red Cells." 22. Preliminary experiments have been performed which show promise as a ILLEGIBLE of determining in-vivo the quantity of ILLEGIBLE I127 in the inorganic form, which may be labelled with I131. Warburg apparatus incubation of various combinations of thyroid intermediated and end products with and without catalysts will be carried out. SPECIAL ACTIVITIES: A training program for physicians was inaugurated with Dr. Herbert C. Allen as the first trainee. He received approximately six months of training on half time in all phases of the activities of the Unit. Ward attendants and nurses have received extensive training in health physics, handling of radioisotopes, disposal of wastes, external measurements and other topics. Our laboratory technicians are graduates in chemistry and have received training in nuclear physics and radiochemistry in the Unit. It seems possible that some of these may receive research credit for this training toward advanced college degrees. A Radioisotope Clinical Evaluation Board meets once weekly for considering the use of radioisotopes for diagnosis or therapy of individual cases. A series of seminars for hospital physicians and laboratory personnel has been held and is continuing as a weekly Radioisotope Discussion Group. Seminars have been presented on the clinical use of radioisotopes to the Physiology Research Seminar of USC Medical School, St. Joseph's Hospital Staff Meeting, Graduate Medical Seminar of L.A. County Hospital and the Medical Faculty Club of UCLA. ************ 21 By increasing the incubation temperature from 37o C to 45o C and increasing the sensitivity of the radioactivity detection techniques it was found that it is possible and practical to use a 15-minute incubation period to tag the red cells used for blood volume determinations instead of the two-hour incubation period at 37o I recommend in the literature. With the aid of p32, studies vera undertaken to determine the rate of uptake, specific activity and organic synthesis on E. Coli. The work now in progress is largely analytical. Starting with tagged lyophilized bacteria, an attempt in being made to separate out and identify various phosphorus fractions such as soluble organic and inorganic P., Phospholipids, ATF, glucose phosphates, ribo- nucleotides and thymonucleotides. Flat copper discs were used wherever possible in counting p32 samples. Scotch tape covers on discs, under standard conditions of geometry, gave an increase of five to seven percent in observed counts per minute. The basic ground work has been laid during the past 8 months on which will be built an extensive investigative program on Insulin Metabolism. WORK COMPLETED DURING THE COMING YEAR: a. Therapy. Three types of diseases will be considered for therapy: 1. Polycythemia Vera (p32) 2. Leukemia (p32) 3. Metabolic dysfunction of the Thyroid (I131) b. Diagnosis. The work on blood volume determination with tagged red blood cells will be continued and investigation directed toward improving the techniques will be extended. c. A series of studies will be initiated concerned with the peripheral vascular circulation. It is planned to use tagged red cells, or iodinated human proteins. d. I131 will be employed as an aid in the diagnosis of thyroid dysfunction. e. Research. All of the problems under investigation during the past year will be continued. Additional investigations will be conducted in: a. The biochemical and physiological phenoma associated with insulin resistance. b. Distribution and metabolism studies on ILLEGIBLE tagged with G35 in experimental animal investigations. c. Tagged antigens for immunochemical studies. d. Studies in diffusion of ions into tissue transplants using radiophosphorus and ILLEGIBLE. e. Cooperative study with the caner central laboratory UCLA Medical School on tagged antibiotics (I131) to determine their distribution in normal and cancerous animals. 23. f. Metabolic studies on the rate of uptake of tagged glycine in antibody molecules under various physiological conditions. (N15 tagged glycine) g. Electron microscopy of thin sections of normal and malignant tissues. h. Distribution studies of diiodoflucrescein containing I131 in experimental animals. SPECIAL ACTIVITIES: A series of lectures and demonstrations on nuclear physics, and tracer techniques will be given during the current year for hospital resident and Radioisotope Unit personnel and interested members of the UCLA Medial School Faculty. Experiences in training Radioisotope Laboratory personnel have proved successful. Consequently, a number of people have been accepted for training during the current year. The first of these trainees will be Dr. DeVenanzi, Assistant Professor of Pathological Physiology, University of Venezuela. Dr. DeVenanzi is expected to arrive about September 1. ************ 24 ABSTRACT OF PROGRESS REPORT SAN FRANCISCO Authorized September 14, 1948; Dr. Wm. W. Saunders, Director PHYSICAL FACILITIES: Laboratory space of approximately 1000-square feet was assigned and made available in February 1949, but great delay has been met in a project for alteration and equipping of this space. Authority for the Manager to carry out the work was released from Central Office Construction Service on September 2, 1949. Some work is being carried out in this space on makeshift tables. Procurement of apparatus has been successfully carried out. Assembly and calibration has been carried out for some of this equipment. Some accounting equipment has been installed in the Basal Metabolism and Electrocardiograph Laboratories and has been in use in these locations. PERSONNEL: In addition to the Director, one full-time Radioisotope Scientist (Biology) has been employed in a Consultant per Annum basis. Dr. Scott (Experimental Radiology) and Dr. Reavis (Internal Medicine) are also Consultants per Annum. A secretary has been employed. When facilities allow, a biochemist and two technicians will be needed. WORK COMPLETED AND IN PROGRESS: a. Therapy. Seven hyperthyroids have been treated with I131, only two of whom had uncomplicated thyrotoxicosis without previous therapy. All are asymptomatic or improved enough to allow further observation. Three patients treated with p32 included one multiple myeloma, one chronic myelogenous leukemia and one chronic lymphatic leukemia. Only the third case has survived and shown improvement. b. Diagnosis. A total of 38 uptake studies using I131 have been made on 29 patients. Of these 15 were euthyroid, 10 hyperthyroid and 4 were hypothyroid. The initial rate of uptake and the maximum uptake have been found accurate as indicators of thyroid function. Radioactive ILLEGIBLE has been tried in localization of brain tumors without success. This is believed to be due to apparatus variation, and this project will be dropped unless a competent neuro-surgeon becomes more interested. No use has been made of p32 in diagnosis. Radiosodium has been used in 10-patients, normal and with various cardiovascular diseases. Special apparatus is being assembled for this necessary rapid high-resolution recording of precardia count rates. 25 Nearing completion is Dr. Wayranch's investigation of the safety of renal biopsy, using particulate chronic phosphate to measure leakage. His results indicate probable safety of the biopsy process. A study is in process, using facilities of Donner Laboratory, of iron metabolism in patients with chemias secondary to neoplastic and chronic inflammatory disease. This study employs Fe59 as a tracer to measure depot concentrations of iron over a long period. WORK CONTEMPLATED DURING THE COMING YEAR: a. Therapy. Present programs using I131 and p32 will be continued and expanded. Consideration is being given to converting the I131 work to a semi-routine procedure administrated by the departments concerned, with stocking and handling of radioactive material being handled by the Unit. b. Diagnosis. Coordination of symptoms and laboratory results in I131 uptake studies will be continued. Circulation time studies using Na24 have just been started and will continue. c. Research. Twenty to fifty selected patients will be studied in the continuation if the Fe59 study referred to at Donner Laboratory. When facilities permit this work will be transformed to this hospital. A study is proposed on the effect of gold salts in rheumatic fever patients. This proposal has been referred to our consultants for recommendation. SPECIAL ACTIVITIES: Much time has been spent in assembling apparatus for convenient working; Dr. Scott has spent a great deal of time in coordination our activity standards with these of Cracker Laboratories and University of California Medical School. We now have workable standard for I131 and p32 and suitable UX2 Beta standards for general calibration work. ************ 26 ABSTRACT OF PROGRESS REPORT FORT LOGAN Authorized May 9, 1949; Dr. Martin G. Goldner, Acting Director PHYSICAL FACILITIES: The Unit is located in a brick building with the Medical Research laboratory. The space assigned to the Unit, totaling 1835-square feet, adjoins the General Medical Research laboratory but is entirely separate from it. Stainless steel-topped desks, stainless steel hoods and other equipment have been built by local firms from Radioisotope Section funds. A request is in process for a small amount to complete necessary partitions. The proposed plan will provide excellent quarters. The work is nearing completion and is expected to be ready for use within the month of September. The desks and hoods were patterned after those designed by Dr. Puck for the University of Colorado Medical Center. PERSONNEL: In addition to the Acting Director, five positions have been authorized; of which three will be filled within the near future. A biochemist, Dr. Joe Meyer, has been employed under the Radioisotope Scientist Series. It is proposed to add a part-time biophysicist and a technician shortly and fill the other two positions later in the year. WORK IN PROGRESS: Work to date has been limited to details of selecting and ordering equipment, and the problem of alteration and installation of fixed equipment. Excellent progress has been made in this ILLEGIBLE. Authority for use of radioisotopes is limited to animal use ILLEGIBLE pending assembly of adequate staff, equipping of laboratory space and development of instrumentation to a satisfactory point. It is hoped that work will progress to the point of allowing diagnostic and therapeutic use of radioiodine and therapeutic use of radiophosphorus within a few months. Several research projects have been under consideration but are not yet sufficiently formulated to present to the Radioisotope Committee for recommendation. Dr. ILLEGIBLE had experience with C14 and hopes to develop some work with this material.