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Biomedical subjects

F A Dilmanian

Publications and source records attributed to F A Dilmanian.

At least 19 recordsLinked to original sources

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

Single-and dual-energy CT with monochromatic synchrotron x-rays.

We explored the potential for clinical research of computed tomography (CT) with monochromatic x-rays using the preclinical multiple energy computed tomography (MECT) system at the National Synchrotron Light Source. MECT has a fixed, horizontal fan beam with a subject apparatus rotating about a vertical axis; it will be used for imaging the human head and neck. Two CdWO4-photodiode array detectors with different spatial resolutions were used. A 10.5 cm diameter acrylic phantom was imaged with MECT at 43 keV and with a conventional CT (CCT) at 80 kVp: spatial resolution approximately equal to 6.5 line pairs (lp)/cm for both; slice height, 2.6 mm for MECT against 3.0 mm for CCT; surface dose, 3.1 cGy for MECT against 2.0 cGy for CCT. The resultant image noise was 1.5 HU for MECT against 3 HU for CCT. Computer simulations of the same images with more precisely matched spatial resolution, slice height and dose indicated an image-noise ratio of 1.4:1.0 for CCT against MECT. A 13.5 cm diameter acrylic phantom imaged with MECT at approximately 0.1 keV above the iodine K edge and with CCT showed, for a 240 micrograms I ml-1 solution, an image contrast of 26 HU for MECT and 13 and 9 HU for the 80 and 100 kVp CCT, respectively. The corresponding numbers from computer simulation of the same images were 26, 12, and 9 HU, respectively. MECT's potential for use in clinical research is discussed.

Acrylates

A modified bottle manikin phantom for in vivo neutron activation analysis.

An artificial skeleton was designed and placed inside a bottle manikin absorber phantom to provide a new reference standard for measurements of total body calcium by in vivo neutron activation analysis at Brookhaven National Laboratory. The composition of the epoxy-based calcium and phosphorus mixture used to construct the skeleton, the dimensions and weight of each bone are given for two phantoms representing an adult male and female. Also, the dimensions, composition, and weights of overlays designed to simulate the influence of obesity on in vivo neutron activation analysis are given for each.

Adult

Calibration of the delayed-gamma neutron activation facility.

The delayed-gamma neutron activation facility at Brookhaven National Laboratory was originally calibrated using an anthropomorphic hollow phantom filled with solutions containing predetermined amounts of Ca. However, 99% of the total Ca in the human body is not homogeneously distributed but contained within the skeleton. Recently, an artificial skeleton was designed, constructed, and placed in a bottle phantom to better represent the Ca distribution in the human body. Neutron activation measurements of an anthropomorphic and a bottle (with no skeleton) phantom demonstrate that the difference in size and shape between the two phantoms changes the total body calcium results by less than 1%. To test the artificial skeleton, two small polyethylene jerry-can phantoms were made, one with a femur from a cadaver and one with an artificial bone in exactly the same geometry. The femur was ashed following the neutron activation measurements for chemical analysis of Ca. Results indicate that the artificial bone closely simulates the real bone in neutron activation analysis and provides accurate calibration for Ca measurements. Therefore, the calibration of the delayed-gamma neutron activation system is now based on the new bottle phantom containing an artificial skeleton. This change has improved the accuracy of measurement for total body calcium. Also, the simple geometry of this phantom and the artificial skeleton allows us to simulate the neutron activation process using a Monte Carlo code, which enables us to calibrate the system for human subjects larger and smaller than the phantoms used as standards.

Body Composition

Subacute neuropathological effects of microplanar beams of x-rays from a synchrotron wiggler.

Microplanar beam radiation therapy has been proposed to treat brain tumors by using a series of rapid exposures to an array of parallel x-ray beams, each beam having uniform microscopic thickness and macroscopic breadth (i.e., microplanar). Thirty-six rats were exposed head-on either to an upright 4-mm-high, 20- or 37-microns-wide beam or to a horizontal 7-mm-wide, 42-microns-high beam of mostly 32- to 126-keV, minimally divergent x-rays from the X17 wiggler at the National Synchrotron Light Source at Brookhaven National Laboratory. Parallel slices of the head, separated at either 75 or 200 microns on center, were exposed sequentially at 310-650 grays (Gy) per second until each skin-entrance absorbed dose reached 312, 625, 1250, 2500, 5000, or 10,000 Gy. The rats were euthanized 2 weeks or 1 month later. Two rats with 10,000-Gy-entrance slices developed brain tissue necrosis. All the other 10,000- and 5000-Gy-entrance slices and some of the 2500- and 1250-Gy-entrance slices showed loss of neuronal and astrocytic nuclei and their perikarya. No other kind of brain damage was evident histologically in any rat with entrance absorbed doses < or = 5000 Gy. Brain tissues in and between all the 312- and 625-Gy-entrance slices appeared normal. This unusual resistance to necrosis is central to the rationale of microplanar beam radiation therapy for brain tumors.

Animals

Calcium supplementation with and without hormone replacement therapy to prevent postmenopausal bone loss.

OBJECTIVE: To determine whether augmentation of dietary calcium is effective in the prevention of early postmenopausal bone loss. DESIGN: Three-arm, placebo-controlled, randomized parallel trial. The study duration was 2.9 +/- 1.1 (SD) years. SETTING: General community. PARTICIPANTS: 118 healthy, white women 3 to 6 years after spontaneous menopause, recruited by community announcement. INTERVENTIONS: Random allocation to daily intake of 1700 mg of calcium (calcium carbonate given in divided doses with meals); placebo; or conjugated equine estrogens (0.625 mg; days 1 to 25), progesterone (10 mg; days 16 to 25), and 1700 mg of elemental calcium daily. Each participant received 400 IU of vitamin D daily. MAIN OUTCOME MEASURES: Total body calcium measured by delayed gamma neutron activation analysis and whole-body counting; bone mineral density of the spine, femur, and radius measured by photon absorptiometry. RESULTS: Bone mineral density declined in the placebo group for the lumbar spine (-2.1%/y; 95% Cl, -3.3 to -0.9), femoral neck (-2.0%/y; Cl, -2.6 to -1.2), trochanter (-1.6%/y; Cl, -2.4 to -0.8), Ward triangle (-2.7%/y; Cl, -3.7 to -1.7), and total body calcium (-2.0%/y; Cl, -2.2 to -1.8). Rates of change were intermediate for calcium augmentation compared with placebo and estrogen-progesterone-calcium but statistically significant compared with placebo for total body calcium (-0.5%/y; Cl, -0.9 to -0.1; P = 0.006) and the femoral neck (-0.8%/y; Cl, -1.4 to -0.2; P = 0.03). CONCLUSIONS: Although less effective than estrogen-progesterone-calcium, calcium augmentation alone significantly retards bone loss from the femoral neck and improves calcium balance in recently postmenopausal women. Dietary calcium augmentation should be recommended as a strategic option in helping to prevent early postmenopausal bone loss.

Analysis of Variance

Calibration for measuring total body nitrogen with a newly upgraded prompt gamma neutron activation facility.

A description is given of the calibration and performance of the upgraded facility at Brookhaven National Laboratory (BNL) for measuring total body nitrogen using the technique of prompt gamma neutron activation analysis. With the improved calibration, total body nitrogen can be more accurately measured not only in normal subjects but also in obese and wasted patients. Body hydrogen is used as an internal standard. We examined the effect of a heavy-water premoderator on the uniformity of composite sensitivity, nitrogen and hydrogen measurement statistics, and dose to the subject. The calibration technique corrects the ratio of nitrogen-to-hydrogen counts measured from the subject for body size. Additionally, a correction for subcutaneous adipose tissue on the nitrogen-to-hydrogen count ratio is introduced. The newly upgraded BNL facility provides precision in counting statistics using a Remcal anthropomorphic phantom filled with a tissue-equivalent solution of 2.1% for a body dose of 0.35 mSv using a 2.5 cm D2O premoderator. The measurements were made at five 20 cm sections, counting for 200 s per section.

Calibration

Body composition and aging: a study by in vivo neutron activation analysis.

Human body composition can be organized into five levels; atomic, molecular, cellular, tissue-system and whole body. Six elements (carbon, nitrogen, calcium, potassium, sodium and chlorine) can be directly measured in vivo at the atomic level using three neutron-activation systems at Brookhaven National Laboratory. When combined with an estimate of total body water, the six elements can be used to quantify the major chemical components at molecular level. In the present report, we first describe the neutron-activation approach to evaluating chemical compartments in vivo. Then, we present an example of how in vivo estimates of human chemical composition can be used to study the validity of two-compartment indirect methods of quantifying total body fat in the elderly. Our studies and the work of other investigators at Brookhaven National Laboratory suggest that neutron activation analysis provides an important opportunity to study the relation between aging and changes in elemental and chemical composition of humans in vivo.

Aging

Low-dose gallium nitrate for prevention of osteolysis in myeloma: results of a pilot randomized study.

PURPOSE: Since osteolysis is a major cause of morbidity in myeloma, we conducted a pilot study to evaluate whether the addition of gallium nitrate to standard antimyeloma treatment could preserve or increase bone mass in patients with osteolytic disease. METHODS: Patients stabilized on cytotoxic therapy were randomized to treatment with gallium nitrate for 6 months, or to observation only for the first 6 months followed by gallium nitrate treatment during the subsequent 6 months. Gallium nitrate was administered in monthly cycles by daily subcutaneous injections (30 mg/m2/d) for 2 weeks, followed by 2 weeks with no therapy, supplemented by an intravenous infusion (100 mg/m2/d) for 5 days every other month. RESULTS: Paired 6-month comparisons were available for seven observation periods and 13 gallium nitrate treatment periods. Total-body calcium assessed by delayed-gamma neutron activation (DGNA) decreased in four of seven patients during observation, but increased in nine of 13 patients during gallium nitrate treatment; the mean difference in total-body calcium (TBCa) between the two groups at 6 months was 3%. Median regional bone density assessed by dual-photon absorptiometry (DPA) declined by 1.4% in patients under observation (range, +6.7% to -18.3%), but was unchanged during gallium nitrate treatment (median change, 0%; range, -10.5% to +14.4%). The group mean vertebral fracture index assessed by lateral spine x-rays decreased by 27% during observation compared with 2% during gallium nitrate treatment. Mean body height decreased by 0.57 inches in the observation group and .06 inches in the gallium nitrate group. Patient self-assessment of bone pain showed that seven of 12 gallium nitrate-treated patients rated themselves as experiencing major reductions in bone pain, compared with zero of seven patients who were observed. One episode of hypercalcemia occurred in a patient under observation. CONCLUSION: Adjuvant treatment with low-dose gallium nitrate attenuates the rate of bone loss in myeloma and may be useful for ameliorating the consequences of skeletal morbidity in patients with cancer-related osteolysis.

Adult

Body-fat measurement in patients with acquired immunodeficiency syndrome: which method should be used?

Malnutrition is common in patients with acquired immunodeficiency syndrome (AIDS), which distorts the chemical contents in the fat-free mass (FFM) and alters the assumptions underlying the traditional methods for calculating body-fat content so that such measurements may not be accurate. In vivo neutron-activation analysis (IVNA) measures FFM independently of the traditional assumptions, thereby providing more accurate measurements of body fat. We compared seven methods for measuring body fat in 18 male patients with AIDS: IVNA, total body water (TBW by 3H2O dilution), total body potassium (TBK by 40K counting), dual-photon absorptiometry (DPA), bioelectrical impedance analysis (BIA), and two well-calibrated anthropometric methods. FatTBW and fatDPA were not significantly different from fatIVNA. FatTBW gave the highest correlation with fatIVNA and the smallest SEE of +/- 1.8% (1.1 kg). The traditional and widely available TBW and the newer DPA method provide reliable estimates of fatIVNA in patients with AIDS.

Absorptiometry, Photon

A 1-y walking program and increased dietary calcium in postmenopausal women: effects on bone.

The effects of a supervised 1-y walking program and increased dietary calcium (milk supplement, 831 mg/d, vs placebo drink, 41 mg/d) on bones were examined in 36 postmenopausal women (60.2 +/- 6.5 y). Trabecular bone-mineral density (BMD) of the lumbar spine (L1-L3), measured by computed tomography, increased by 0.5% in exercising women (n = 18) and decreased by 7.0% in sedentary women (n = 18; P = 0.02). Femoral-neck BMD measured by dual-photon absorptiometry (DPA) increased by 2.0% in women consuming high dietary calcium (n = 18) and decreased by 1.1% in those on moderate calcium intake (n = 18; P = 0.001). Neither exercise nor dietary calcium had an effect on lumbar spine (L2-L4) measured by DPA, distal radius measured by single-photon absorptiometry, or total body calcium measured by in vivo neutron activation. The varying proportions and rates of turnover of trabecular and cortical bone from one site to another suggest that exercise and high dietary calcium may preferentially alter bone density at different skeletal sites.

Absorptiometry, Photon

Chemical and elemental analysis of humans in vivo using improved body composition models.

Six chemical compartments [water, protein, mineral (osseus and cellular), glycogen, and fat] consisting of 11 elements (N, C, Ca, Na, Cl, K, H, P, O, S, and Mg) comprise greater than or equal to 99% of body weight in living humans. The combination of three neutron-activation systems, whole body 40K counting, and 3H2O dilution at Brookhaven National Laboratory now potentially makes it possible to quantify greater than or equal to 96% of the chemical and elemental determinants of body weight in vivo. The aims of the present study were 1) to develop 6- and 11-compartment chemical and elemental models, respectively, and 2) to evaluate these models in a group of 20 healthy adults. Results demonstrated that body weight estimated from either chemical or elemental components was highly correlated with (both r = 0.97, P less than 0.001) and on average differed by less than 4% from actual body weight. The compartmental results obtained using the chemical model were also evaluated by comparing calculated and actual body density (Db) estimated by underwater weighing. Calculated Db [1.041 +/- 0.017 (SD) g/ml] agreed closely and was highly correlated with actual Db (1.039 +/- 0.018 g/ml; r = 0.82; P less than 0.001). Hence a near-complete chemical and elemental analysis of living human subjects is now possible and, with potential future refinements, represents an important opportunity to quantify the effects of gender, aging, and ethnic status on body composition.

Adult

High precision in-vivo neutron activation analysis: a new era for compartmental analysis in body composition.

We have focused on two topics in body composition research. The first is basic: we must quantitatively define the interrelationships of the body compartments to one another in health before studying these relationships in disease. The precisions now available can enable us to get to do this work, over the full range of age, race, and occupational diversity. The second direction is more modest and more technical, but nonetheless important. It is the calibration and validation of surrogate measurement methods suitable for field research conditions, doctors' offices, intensive care units, etcetera. Our methods have advanced in fundamental ways. We have an obligation to see them applied effectively.

Adipose Tissue