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Pacific Northwest Laboratories Human Subjects Comni tteeolom t\sC Ib - 15 Additional Studies o f Regional Muscle Mass Changes i n Humans by Measuring the Naturally Occurring 40K The Human Subjects Committee has recently given approval t o make ‘+OK measurements on volunteers participating i n exercise programs toin - crease muscle mass. This letter is a request for this approval t o be extended t o patients of the local Orthopedic and Fracture Group Need and Purpose of Work The 4 0 K measurements on the upper legs of exercising volunteers have resulted i n some interesting observations and an indication of some muscle mass changes, but have not yet demonstrated that ‘+OK is or is not a good measure of muscle mass. vat ions are 1 isted below: Some of the more important obserAlthough the standard deviation of the count r a t e should be +1%, subjects who are not on an exercise program and whose muscle mass is presumably changing very slowly show random deviation of 5 or 6% during a period of a few weeks. If a subject has two successive 15-minute counts, the second count i s always lower than the first which indicates a possible transfer of ‘+OK containing fluids o u t of the legs into the upper regions of If a person’s leg i s counted several times during a day, his count i n the afternoon is usually lower than i n the morning. If a person is counted and then does deep knee bends u n t i l the legs are fatigued, an immediate second count will be as much as ‘6%higher than the count made before the exercise. This higher count is accompanied by more pressure of the legs against the positioning devices which hold the legs in place and indicates increased blood flow into the fatigued muscle. The 6% increase i n count rate cannot be accounted for by blood flow alone since (1) the blood normally contains only 8%o f the total body K and a l l of the blood or even a large fraction cannot be i n the legs a t one time and ( 2 ) increased volume of the legs should result i n a few percent reduction i n count due to self-absorption. If one subtracts out the self-absorption, the change in40K count would be even greater. This suggests that intracellular potassium may not be as constant i n concentration as normally assumed and there may be significant transfer o f K temporari ly to fatigued muscles.
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5) Volunteers from a health spa do not make good subjects for renot committed enough to the purposes of the study. already significant stress on these muscles i n normal walking and There is still a need t o determine if 40K can be used t o measure regional muscle mass and to determine the conditions under which it is useful for this purpose. tent and meaningful measurements they must be done a f t e r several hours of rest when the body is in a state of equilibrium with respect more recently NIH through their Diet, Nutrition and Cancer Program have expressed interest in these types of measurements. They are planning t o spend about $750 Kin the development o f these types of methods (see attached copy of proposed projects) and will be spending millions on studies which will use these methods. Under the arrangements which existed they were 6) The legs a r e a poor place to increase muscle mass since there i s I t may be that in order to obtain consisNASA is still vitally interested i n these studies and In discussions w i t h Drs. Pettee, Field, and Zirkle of the Tri-City Orthopedic and Fracture Group, Inc., they indicate that some of their patients lose upto 2" circumference i n their upper leg during the period i n which the leg isina cast. loss of muscle mass which i s slowly replaced after the cast i s should be easy to study. encourage appropriate patients t o allow 4 0 K measurements on their legs. The attached description will be given t o the patient who will then decide i f he will volunteer for the study. t o extend the age limit for these volunteers down t o 1 6 years of age since injuries are more comnon i n this age group and they regenerate lost muscle mass faster. This corresponds to about 20% This could provide a significant muscle mass change which These physicians are willing t o refer and We would like The measurement procedure will be the same as that used with the exercise volunteers except t h a t only one of the legs will be counted rather than both. The volunteers will be counted once each week for the f i r s t month and then twice a month until the end of the study which may last three o r The volunteers will be paid at the rate of $10 per measurement plus an additional $5 per measurement if they continue t o the end of the study.
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The volunteers will sign a consent form and i f under 21 their parents will sign the form before measurements are started. The proposed consent form i s attached. We will not require a physical examination since these volunteers are
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RESEARCH AREA: Therapy Study o f the changes i n body composition produced by OBJECT IVE : To quantify the changes. i n major body compartments induced by cancer development and t o develop the technique necessary for this evaluation. Adequate clinical data with direct measurements o f body pools are lacking, making i t impossible t o determine whether a1 te rations in a specific subcomponent (e.g. hemoglobin o r serum albumin) are manifestations of a generalized or a specific target of cachexia. clinical data are therefore needed. This project will cover three separate but related areas. To answer immediate questions on the alte7ation of body conpartments, long-term studies using currently available techniques, in clu d in q 4oK dpterminati'on, w i 11 be conducted. A t the same time, neutron activation studies t o develop techniques and procedures for who1 e-body n i trogen determinations will be begun. In addition techniques for stable isotope analysis, with emphasis on h i and 13C, will be evaluated and developed as necessary f o r use as a research and diagnostic tool. A report evaluating the effects of specific cancer types on body compartments will be produced. Other reports will describe the feasibility of using neutron activation and stable isotope analysis for future metabol i c studies. Expertise with available techniques, including 4oK deter - minations; cancer and control patients ; and ability to develop and apply instrumentation techniques and procedures $250,000 for year one
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MUSCLE MEASUREMENT STUDY In several types of diseases and during spaceflight there i s a significant loss of muscle from the body. has been asked by the National Aeronautics and Space Administration (NASA) and the National Institutes of Health (NIH) to study and develop methods to measure the amount o f muscle loss which may occur. Your unfortunate leg injury and placement i n a cast has probably resulted in some loss o f muscle due to the lack of normal stress on your leg. using your leg this muscle will be gradually replaced. Scientists at Battelle-Northwest would like to measure the muscle content of your leg during this muscle rebuilding period. The measurements would be done once each week and would require about 20 to 30 minutes. The measurement consists of lying on a bed for about 20 minutes with your leg between two scintillation detectors which measure the very small amount of naturally occurring radioactivity which is associated with all muscle tissue. There is no pain, X-rays, injections, or other body insults. The measurements will be done at the Battelle Whole Body Counter located two blocks from the Orthopedic and Fracture Group building (see attached map). Upon removal of your cast and as you again start If you would like to make a personal contribution to medical science and the NASA Space Program by allowing measurement of your leg, it would be very much appreciated. The measurement period would extend for a period of two to three months and would be done once per week for the first month and then two times per month thereafter. your time and effort Battelle-Northwest will pay $10 for each measurement and an additional $5 per measurement i f you continue to the end of the study. to the \/hole Body Counter or call Mr. H. E. Palmer at 942-6102 between For additional information and details please come
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INFORMED CONSENT FOR MUSCLE MEASUREMENT STUDY I agree t o participate ina study for the purpose of measuring changes i n muscle mass i n the upper and lower legs which may have been caused by my leg injury. I will allow the muscles of my legs t o be measured once each week for the first month and twice each m o n t h for the remainder of the study which will continue f o r three t o four months. The measurements will consist of placing radiation detectors above and below the legs and measuring the natural potassium which i s associated with all muscle tissue. The information obtained from this study will be used t o develop methods of measuring muscle mass changes which may develop i n astronauts during spaceflight and in parti - There are no known risks involved. T h e volunteers may withdraw from the study a t any time without penalty of prejudice and will be paid according t o the portion of the experiment completed. I understand the above procedure and have had a n opportunity t o As parent or guardian of I consent t o his participation in this study. 9