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Biomedical subjects

D Vartsky

Publications and source records attributed to D Vartsky.

At least 19 recordsLinked to original sources

In vivo determination of prostatic zinc: phantom feasibility study.

This paper describes a phantom-based feasibility study for a potential in vivo determination of zinc in prostate, which could bring about improved diagnosis of prostate cancer. An x-ray fluorescence topographic technique was developed, which will permit determination of the Zn content in the prostate through the rectum, namely behind a 2-3 mm thick layer of the rectal wall. The topographic approach, together with a reconstruction method developed here, minimizes the interference of Zn from non-prostatic tissue. The phantom studies show that it will be possible to determine Zn in a prostatic compartment behind a few mm thick layer of tissue using a specially designed transrectal probe. Such a probe is currently under development in our laboratories.

Feasibility Studies↗

Prostatic zinc and prostate specific antigen: an experimental evaluation of their combined diagnostic value.

PURPOSE: In cancer affected prostate cells lose the ability to concentrate zinc, resulting in a substantial decrease in Zn in the prostate. We investigated the possibility of using prostatic zinc combined with prostate specific antigen (PSA) as a novel tool for the reliable diagnosis of prostate cancer. MATERIALS AND METHODS: Using the x-ray fluorescence method the Zn concentration was determined in vitro in prostate samples extracted by surgery from 28 patients. Clinical records included age, serum PSA, sextant prostate needle biopsy, previous medical therapy, surgical procedure and histological findings. RESULTS: A new relationship was found between Zn in prostate tissue and PSA in blood, which allows improved separation between prostate cancer and benign prostate hyperplasia, and might have a significant impact on the reliable diagnosis of prostate cancer. CONCLUSIONS: Zn concentration is not uniform even in the same anatomical region of the prostate, so that a number of measurements at various locations are required for a diagnostic procedure. The most interesting finding in this study is the relationship between Zn concentration and PSA. A combination of these parameters represents a significant improvement on the diagnostic value of each of them separately and provides a powerful tool for more accurate diagnosis. Although the method may be applied in vitro on biopsy samples, our study underlines the importance of developing a facility for in vivo Zn determination in the prostate.

Aged↗

Gamma resonance absorption. New approach in human body composition studies.

The main stream of body elemental analysis is based on the delayed, prompt, and inelastic neutron interactions with the main elements found in the human body, and subsequent analysis of the measured delayed or prompt gamma ray spectra. This methodology traditionally was, and still is, applied for whole body analysis and requires relatively high radiation doses. A new method, based on gamma nuclear resonance absorption (GNRA), is being established at Brookhaven National Laboratory as part of its body composition program. The method is element specific with a high tomographic spatial-resolution capability, at a small fraction of the radiation dose used in the current system. The new system, with its components and capabilities, is described below.

Adult↗

Gamma ray nuclear resonance absorption: an alternative method for in vivo body composition studies.

We have evaluated gamma ray nuclear resonance absorption (gamma-NRA) on nitrogen, a mature technology proposed and developed by Soreq NRC for detecting explosives, as an alternative to neutron activation for in vivo assaying of body nitrogen. The principles of the gamma-NRA method are outlined, and a test facility constructed at McMaster University's Accelerator Laboratory is described. The results of a feasibility study recently performed there on phantoms and animal tissue are presented and discussed. gamma-NRA is a full imaging technique that essentially constitutes element-specific absorptiometry--i.e., it can generate projections of the mass distribution for a specific element, along with a conventional radiograph of the patient. From the transmission profile of an individual scanned by 9.17 MeV gamma rays, local or whole body nitrogen content can be determined via the resonant attenuation undergone when the beam encounters regions of nitrogen concentration. The advantages of gamma-NRA over neutron activation are (a) radiation doses delivered to the body are at least one order of magnitude lower, thus allowing repeated measurements on individual patients and also rendering the method ethically acceptable for application to children; (b) gamma-NRA is inherently free from uncertainties related to nonuniform distributions of the element in question within the body; (c) it is applicable to patients of varying size and shape; and (d) it yields both nitrogen images and conventional radiographic images of the body.

Animals↗

Improvement of the prompt-gamma neutron activation facility at Brookhaven National Laboratory.

The prompt-gamma neutron activation facility at Brookhaven National Laboratory was upgraded to improve both the precision and accuracy of its in vivo determinations of total body nitrogen. The upgrade, guided by Monte Carlo simulations, involved elongating and modifying the source collimator and its shielding, repositioning the system's two NaI(Tl) detectors, and improving the neutron and gamma shielding of these detectors. The new source collimator has a graphite reflector around the 238PuBe neutron source to enhance the low-energy region of the neutron spectrum incident on the patient. The gamma detectors have been relocated from positions close to the upward-emerging collimated neutron beam to positions close to and at the sides of the patient. These modifications substantially reduced spurious counts resulting from the capture of small-angle scattered neutrons in the NaI detectors. The pile-up background under the 10.8 MeV 14N(n, gamma)15N spectral peak has been reduced so that the nitrogen peak-to-background ratio has been increased by a factor of 2.8. The resulting reduction in the coefficient of variation of the total body nitrogen measurements from 3% to 2.2% has improved the statistical significance of the results possible for any given number of patient measurements. The new system also has a more uniform composite sensitivity.

Gamma Rays↗

A proposed method for in vivo determination of lithium in human brain.

A method for measuring Li in vivo in human brain is presented. The technique is based on the measurement of tritium gas exhaled by the subject following neutron irradiation of the organ of interest. The gas collection facility used to separate minute amounts of tritium from the breath is described. Methods for reducing the background levels of tritium were investigated. The limit of detection of the system is estimated to be 350 micrograms of Li for the whole brain for a dose of 10 mSv. This detection limit is sufficient for the study of patients treated with lithium compounds, but is too high to study 'normal' brain lithium content. The rate of elimination of tritium gas from the body was also investigated in animal studies. The method also appears suitable for the measurement of lithium levels in the kidney.

Air↗

Whole body cellular and collagen nitrogen in healthy and wasted man.

The classical literature shows that wasting of body protein takes place mainly from the cellular compartment leaving high proportions of extracellular collagen. Whole body nitrogen ( WBN ) is proportional to whole body protein (cellular + extracellular) while whole body potassium ( WBK ) is almost entirely intracellular. WBK might be an adequate index of cellular wasting. WBN was measured by neutron activation and WBK by counting 40K in 29 healthy males and 131 male and female patients with wide ranges of body composition. Our wasted patients with Crohn's disease or ulcerative colitis, had higher WBN / WBK ratios than matched healthy controls and the difference between the two groups was in the cellular ratio (23.6 mol of N/mol of K, 0.33 g of N/mmol of K, 3 mmol of K/g of N). A multiple regression model for all the subjects represented cellular nitrogen by a term in WBK and extracellular nitrogen by simple anthropometric measurements. The partial regression coefficient of WBN on WBK was 22.6 +/- 1.1 (SE) mol of N/mol of K; this was also similar to the cellular ratio. Our results were compatible with extracellular protein (mainly collagen, which is 35% of normal whole body protein) remaining resistant to wasting even when severe loss of cellular protein occurs. The high ratios of WBN / WBK in wasted patients can be explained by this disproportionate wasting of cellular substances and they do not imply alterations in the cellular N/K ratio. We suggested that the stable ratio of WBK to cellular protein makes it an effective index of cellular wasting. The resistance of collagen to wasting and the preponderance of extracellular mass in the fat-free mass of wasted subjects, make WBN and fat-free mass unreliable guides to the extent of wasting.

Activation Analysis↗

An improved calibration for the in vivo determination of body nitrogen, hydrogen, and fat.

Additional investigation of the authors' original technique for measuring total body nitrogen by prompt gamma neutron activation has demonstrated the need for certain changes in the calibration procedures in order to apply the method to studies of patients with abnormal metabolism. In the present technique, total body nitrogen, hydrogen, and fat were derived, simultaneously, from data obtained by neutron capture gamma-ray analysis combined with the measurements of body weight, total body water, and total body calcium. In this improved calibration technique total body nitrogen is more accurately measured, not only in normal subjects, but also in obese subjects and in patients with marked changes in hydration, such as cancer patients. The fat values calculated do not rely on a fixed relationship of total body water or total body potassium with lean body mass as in the previous studies, but are calculated as the difference between body weight and the sum of body water, protein and bone mineral ash. This improved technique has been applied to the study of three groups of subjects, the general population with a normal weight distribution and two extremes represented by obese and cancer patients.

Adipose Tissue↗

Effects of caloric restriction on body composition and total body nitrogen as measured by neutron activation.

The purpose of this study was to compare the effects of two isocaloric diets (800 Kcals) on the changes in body composition during weight reduction. While the protein content of both diets was 70 g, the carbohydrate content of diet A was 10 g and that of diet B was 70 g. The various parameters of body composition were determined as follows: Total body potassium (TBK) by 40K counting, total body water (TBW) by the tritiated water technique, total body nitrogen (TBN) by prompt gamma neutron activation analysis (PGNAA) and total body fat was estimated by measuring the skinfold thickness. Routine serum chemistries were performed every 2 wk and serum insulin and triiodothyronine by radioimmunoassay were done at 4-wk intervals. Seventeen obese women who were at least 30% above ideal body weight volunteered for the outpatient study, (group A--10 subjects, group B--7 subjects). At the end of the 12 wk study, the percent changes in the above parameters of body composition were not significantly different for the two groups. The biochemical changes were consistent with the degree of caloric restriction. We conclude that: (1) the technique of prompt gamma neutron activation analysis can be used effectively to determine long term changes in total body nitrogen during weight reduction, (2) loss of lean tissue (water, potassium and nitrogen) as well as fat tissue occurred during weight reduction. The loss of TBN in absolute quantities was less for diet A compared to diet B; however, there was no significant difference between the two diets when the data was expressed as a percent change from the baseline values, and (3) TBK determination probably provides the best estimate of total body fat.

Adult↗

Evaluation of body composition and nitrogen content of renal patients on chronic dialysis as determined by total body neutron activation.

Total body protein (nitrogen), body cell mass (potassium), fat, and water were measured in 15 renal patients on maintenance hemodialysis (MHD). Total body nitrogen was measured by means of prompt gamma neutron activation analysis; total body water was determined with tritium labeled water; total body potassium was measured by whole body counting. The extracellular water was determined by a technique utilizing the measurement of total body chloride and plasma chloride. When compared with corresponding values of a control group of the same age, sex, and height, the protein content, body cell mass, and total body fat of the MHD patients were within the normal range. The only significant change was an increase in the extracellular water/body cell mass ratio in the male MHD patients compared to the controls. The lack of significant difference of the nitrogen values of the MHD patients compared to matched controls suggests that dialysis minimizes any residual effects of uremic toxicity or protein-calorie malnutrition. These findings further suggest that there is a need to reevaluate the traditional anthropometric and biochemical standards of nutritional status for MHD patients. It was concluded that it is particularly important to measure protein stores of MHD patients with low protein intake to ascertain nutritional status. Finally, in vivo measurement of total body nitrogen and potassium for determination of body composition provides a simple, direct, and accurate assessment of the nutritional status of MHD patients.

Adipose Tissue↗

Indexes of body cell mass: nitrogen versus potassium.

In vivo neutron activation has provided investigators with a powerful tool for research on body composition. Total-body nitrogen (TBN), total-body potassium (TBK), and total-body water (TBW) were measured in 133 normal subjects. TBN, measured by neutron activation, is a measure of total-body protein, an index of body cell mass. TBK, also measured by a nuclear reaction, is an index of body cell mass as well as lean body mass. The mass and protein content of two compartments, muscle and nonmuscle lean tissue, were determined from the combined TBN-TBK data by compartmental analysis. In this study, nitrogen was separated into the actively metabolizing body cell mass component and the slowly metabolizing structural component. The TBK, which is 95% intracellular, was found to be more closely related to the actively metabolizing nitrogen than to TBN. The relationship of body cell mass, a concept originally proposed by Moore, to lean body mass, is shown through the relationship of TBN and TBK. The clinical significance of this study, is that TBK is the more sensitive and reliable indicator of changes in body cell mass. Maximum information on body composition, however, is obtained by the measurement of both TBK and TBN.

Adult↗

A facility for in vivo measurement of lithium.

A facility for measurement of Li in-vivo based on measurement of exhaled HT gas has been constructed and tested. Li present in the brain of therapeutically treated individuals could be measured with a dose to the brain of 1 rem. It will be possible to locate grossly the non-uniformity of Li, left-right or front-back sides of the brain, by choosing the proper energy of neutrons. Experiments with larger animals such as sheep are planned.

Body Fluids↗

Applications of nuclear technologies for in vivo elemental analysis.

The objectives of this Department of Energy sponsored program are (1) to improve existing nuclear techniques, and (2) to develop new techniques for the analysis and solution of both medical problems and those associated with environmental pollution. Measurement facilities developed, to date, include a unique whole body counter, (WBC); a total body neutron activation facility (TBNAA); and a partial body activation facility (PBNAA). A variation of the prompt gamma neutron activation technique for measuring total body nitrogen has been developed to study body composition of cancer patients and the effect of nutritional regimens on the composition. These new techniques provide data in numerous clinical studies not previously amenable to investigation. The development and perfection of these techniques provide unique applications of radiation and radioisotopes to the early diagnosis of certain diseases and the evaluation of therapeutic programs. The PBNAA technique has been developed and calibrated for in vivo measurement of metals. Development has gone forward on prompt gamma neutron activation for the measurement of cadmium, x-ray fluorescence (XRF) for measurement of lead, and nuclear resonance scattering (NRS) for measurement of iron. Other techniques are being investigated for in vivo measurement of metals such as silicon and beryllium. Cardinal to all toxicological studies of Cd and other metal pollutants is an accurate and sensitive noninvasive technique for measuring organ burdens. In keeping with the mission of Brookhaven, these facilities have been made available to qualified scientists and members of the medical community throughout the world.

Adult↗

Changes in body composition of cancer patients following combined nutritional support.

The effects of combined nutritional support (parenteral, enteral, and oral) were measured in cancer patients unable to maintain normal alimentation. Changes in body composition were quantified by measurement of total body levels of nitrogen, potassium, water, and fat. The protein-calorie intake of the patients was also evaluated by dietary survey (4-day recall). Standard anthropometric and biochemical measurements for nutritional assessment were obtained for comparison. The dietary evaluation indicated that the dietary supplementation for all patients was more than adequate to meet their energy requirements. Almost all patients gained weight on the combined nutritional support regimens. Determination of body composition indicated that change in body weight was equal to the sum of the changes in body protein, total body water, and total body fat. The findings from the anthropometric nutrition indices (arm muscle circumference and triceps skinfold) were consistent with the results of the body composition study. Information on the nature of the tissue gained was obtained by comparison of body composition data with the ratio of protein:water:lean body mass for normal tissue. The mean gain of protein in the cancer patients was quite small (0.3-0.6 kg). The main change in body weight appeared to be the result of gains in body water and body fat. The total body nitrogen to potassium ratio served to define the extent of tissue anabolism following hyperalimentation. The ratio dropped in the cancer patients following hyperalimentation toward the value of the control subjects on ad libidum diets. The body compartment techniques described have demonstrated their usefulness in determining the effects of hyperalimentation on cancer patients.

Adipose Tissue↗

Total body nitrogen in health and disease: effects of age, weight, height, and sex.

Total body levels of nitrogen were measured by prompt-gamma neutron activation analysis in 136 healthy adults in the general population (age 20 to 80 years), in 55 cancer patients, and in 20 obese subjects. In order to evaluate the TBN values for the patients, it was necessary to normalize the data for possible differences due to body habitus. This normalization was defined as the ratio of the measured nitrogen level to a predicted nitrogen level derived from the normal population. The parameters of sex, age, Ht, Wt, and fat were used to calculate expected "normal" values of nitrogen. For the cancer patients, an average TBN deficit of less than 10% was observed. Individual patients, however, showed deviations from the TBNp value as large as 28%. For obese patients, the TBN values were normal to slightly high. When adjusted for body size, the deficit of TBN in the cancer patients was approximately half that observed for TBK.

Adult↗