Measurement Of Total Body Nitrogen Research Articles

Assessment of the associated particle prompt gamma neutron activation technique for total body nitrogen measurement in vivo

Total body nitrogen (TBN) can be used to estimate total body protein, an important body composition component at the molecular level. A system using the associated particle technique in conjunction with prompt gamma neutron activation analysis has been developed for the measurement of TBN in vivo. The system uses a compact D, T neutron generator (~107 n/s) coupled to an internal alpha-particle detector, and a counting system with six bismuth germinate detectors. 14 Subjects were scanned from shoulders to hips (20 min scan time, <0.4 mSv dose) generating complex spectra dominated by signals from C, O, H, and N, with significant peak overlap. Fractional contributions from these elements to regions of interests (ROI) spanning a 4–8 MeV range were determined by algorithms comparing ratios of interrelated ROIs. In addition, multi-component least squares fitting was done to further resolve individual peak activities (MATLAB R2011b). Total body potassium (TBK) was also measured using a whole body gamma counter. Predicted TBN values, based on fat-free mass estimated from TBK, were compared to measured TBN results. Measured versus predicted results for all subjects were not statistically different. Separating subjects by gender also showed no difference between measured and predicted values. The associated particle system showed good agreement with predicted TBN values, but measurement precision was not better than that commonly seen in traditional prompt gamma thermal neutron activation analysis systems.

Design considerations for a neutron generator-based total-body irradiator

The prompt- and delayed-gamma neutron activation techniques have been used for the non-invasive measurement of human body composition. In recent years, neutron irradiators have used only transuranic isotopic sources (238PuBe, 241AmBe, 252Cf). However, in today’s security-minded environment, the use of alternate neutron sources may provide some advantages. We have examined several designs for an irradiator that would use a high-output, miniature D-T neutron generator (MF Physics). The use of this type of neutron source will lessen the storage, security, and transport issues associated with continuous-output isotopic neutron sources. To determine the scientific impact of this decision, we have performed Monte Carlo simulations (MCNP-4B2; Los Alamos National Laboratory) to aid in the design of the irradiator system, evaluating shielding materials, collimation, and source-to-subject distance, for the measurement of total body nitrogen (TBN). Based on internal flux distributions within the simulated body region of a subject, several design options were identified. The final design will be selected based on the optimization of precision, dose, and exposure time.

Composition of gestational weight gain impacts maternal fat retention and infant birth weight

Objective The purpose of this study was to evaluate how changes in gestational weight and body composition affect infant birth weight and maternal fat retention after delivery in underweight, normal-weight and overweight women. Study design We assessed the body composition of 63 women (low body mass index, 17 women; normal body mass index, 34 women; and high body mass index, 12 women) on the basis of measurements of total body nitrogen by prompt-gamma activation analysis, total body potassium by whole body counting, and a multicomponent model based on total body water by deuterium dilution, body volume by densitometry, and bone mineral content by dual energy x-ray absorptiometry (DXA) before pregnancy, at 9, 22, and 36 weeks of gestation, and at 2, 6, and 27 weeks after delivery. Infant weight and length were recorded at birth; infant anthropometry and body composition by DXA were assessed at 2 and 27 weeks of age. Results Gestational weight gain was correlated significantly with gains in total body water, total body potassium, protein, fat-free mass, and fat mass ( P = .001-.003). Gains in total body water, total body potassium, protein and fat-free mass did not differ among body mass index groups; however, fat mass gain was higher in the high body mass index group ( P = .03). Birth weight was correlated positively with gain in total body water, total body potassium, and fat-free mass ( P<.01), but not fat mass. Postpartum weight and fat retention were correlated positively with gestational weight gain ( P = .001) and fat mass gain ( P = .001) but not with total body water, total body potassium, or fat-free mass gain. Conclusion Appropriate, but not excessive, gestational weight gain is needed to optimize infant birth weight and minimize maternal postpartum fat retention.

Validity of subjective global assessment as a nutritional marker in end-stage renal disease

Subjective global assessment (SGA) is a widely available clinical tool established to be of prognostic value in patients with end-stage renal disease (ESRD). Although it is reported to reflect a patient's nutritional status, its direct relationship to nutrition has not been determined. The aim of this study is to compare SGA with the gold standard for nutrition, total-body nitrogen (TBN) level, and thus determine the validity of SGA as a marker of nutritional status in patients with ESRD. Seventy-six consecutive dialysis patients referred from the renal service for routine measurement of TBN underwent simultaneous assessment of SGA determined by two independent examiners. Both examiners were blinded to TBN results. Only a moderate level of agreement was found in SGA score between the two examiners (weighted κ score, 0.6). When patients were stratified into three nutritional groups determined by their SGA score, mean TBN values for each group by observer differed significantly (P = 0.0008 and P = 0.02, respectively). However, a significant statistical trend of worsening nutrition across SGA strata was found only for observer 2 (P = 0.049). Test performance of SGA as a predictor of malnutrition using a cutoff score of B (SGA = B or C) or C (SGA = C) was poor (positive likelihood ratios [LRs], 0.7 to 2.3; negative LRs, 0.5 to 1.0). Therefore, SGA appears not to improve the posttest probability of detecting malnutrition. SGA may differentiate severely malnourished patients from those with normal nutrition, but is not a reliable predictor of degree of malnutrition. © 2002 by the National Kidney Foundation, Inc.

Body composition in adolescents with anorexia nervosa

Malnourished patients with anorexia nervosa have altered body composition characterized by depletion of fat and fat-free mass. The objectives of this study were to assess the body composition of adolescents with anorexia nervosa compared with that of control subjects and to investigate the relation between simple anthropometric measures and reference techniques for measuring body composition. Twenty-three adolescent females with anorexia nervosa aged 15.46 +/- 1.34 y (x +/- SD) were studied. Body composition was measured by anthropometry, dual-energy X-ray absorptiometry (DXA) (for body fat), and prompt gamma in vivo neutron activation analysis [for total body nitrogen (TBN)]. Twenty-five female subjects provided the control DXA data. TBN measurements were compared with prediction equations based on sex, height, age, and weight. Anorexia nervosa patients had significantly lower weight (40.2 +/- 4.6 kg), body mass index (in kg/m(2): 15.3 +/- 1.2), percentage of body fat (DXA) (13.8 +/- 5.8%), percentage of TBN predicted for age (73 +/- 10%), trunk fat (2.1 +/- 1.0 kg), leg fat (2.6 +/- 1.1 kg), and trunk-to-leg fat ratio than did control subjects (P < 0.05). In anorexia nervosa patients, significant correlations were found between triceps skinfold thickness and percentage of body fat (r = 0.83), body mass index and percentage of body fat (r = 0.46), and body weight and TBN (r = 0.84, P < 0.05). Hospitalized adolescent females with anorexia nervosa are depleted of total body fat and protein. We identified 3 simple anthropometric measures (triceps skinfold thickness, BMI, and body weight) that can be used to assess body composition and nutritional status in malnourished adolescents with anorexia nervosa.

Assessment of background hydrogen by the Monte Carlo computer code MCNP-4A during measurements of total body nitrogen.

The use of a hydrogen internal standard to enable the estimation of absolute mass during measurement of total body nitrogen by in vivo neutron activation is an established technique. Central to the technique is a determination of the H prompt gamma ray counts arising from the subject. In practice, interference counts from other sources--e.g., neutron shielding--are included. This study reports use of the Monte Carlo computer code, MCNP-4A, to investigate the interference counts arising from shielding both with and without a phantom containing a urea solution. Over a range of phantom size (depth 5 to 30 cm, width 20 to 40 cm), the counts arising from shielding increased by between 4% and 32% compared with the counts without a phantom. For any given depth, the counts increased approximately linearly with width. For any given width, there was little increase for depths exceeding 15 centimeters. The shielding counts comprised between 15% and 26% of those arising from the urea phantom. These results, although specific to the Swansea apparatus, suggest that extraneous hydrogen counts can be considerable and depend strongly on the subject's size.

Total body protein in chronic diseases and in aging.

Substantial losses of total body protein (TBP) can occur in chronic diseases and in aging. Such losses impact negatively on immunity and quality of life, and on growth rates in children. Direct measurements of total body nitrogen (TBN) monitor the integrated changes in TBP over time and allow comparison with normal subjects. TBN assessment via neutron capture analysis is therefore the gold-standard method of TBP estimation, so that risk factors for protein deficit can be identified and patient management optimized. The nitrogen index (NI) can be used to predict prognostic outcome: an NI < 0.9 is associated with substantial wasting in HIV disease, an NI < 0.8 predicts significant pathophysiology in chronic renal failure, and a low NI is predictive of neutropenia in breast-cancer patients. These findings emphasize the central importance of adequate protein stores in recovery from disease or in maintaining quality of life. Aging appears to involve a gradual loss of TBP throughout adulthood. Cross-sectional data suggest that TBP declines curvilinearly with age, such that there is an accelerated decline after 65 years of age. However, longitudinal data are scarce, and little is known about the relative loss of visceral protein, as opposed to skeletal muscle protein. More clearly-defined data are essential if the effects of aging per se are to be separated from the effects of chronic disease. A further complication is the knowledge that physical activity also declines with age. Thus sarcopenia, the loss of skeletal muscle mass, could primarily result from disuse rather than aging. The economic impact of unsuccessful aging places a pressing need for multicompartment data in longitudinal study designs.

The predictive value of body protein for chemotherapy-induced toxicity.

The use of body surface area in determining chemotherapy dosing, particularly in the obese, remains controversial. Total body nitrogen (TBN) measurement in patients with serious illness has been suggested to be an accurate predictor of clinical course. The ability of TBN to predict chemotherapy-induced neutropenia was examined in the current study. TBN measurements were performed in 31 female outpatients with breast carcinoma who were undergoing standard cyclophosphamide, methotrexate, and 5-fluorouracil (CMF)-based chemotherapy (median age, 48 years; range, 26- 77 years). TBN was measured using the in vivo neutron capture analysis technique on Day 1 of Cycles 2-6. The chemotherapy toxicity index used was the absolute neutrophil count nadir (ANCN). Neutropenia was defined as an ANCN < 1.0 x 10(9)/L. The nitrogen index (NI) (TBN expressed as a percentage of age-, gender-. and height-matched healthy patients) then was compared with the corresponding ANCN values. Using receiver operating characteristics analysis, a "cut-off" value of NI = 0.89 was found. In this group of patients, when the NI was < 0.89, 11 of 13 courses in 7 patients (85%) led to an ANCN of < 1.0 x 10(9)/L, and when the NI was > 0.89, 29 of 109 courses (27%) led to an ANCN of < 1.0 x 10(9)/L (P < 0.0001). In this small group of breast carcinoma patients, the NI was found to be the most powerful predictor of neutropenia after CMF-based chemotherapy. The authors conclude that NI may be a useful clinical tool in identifying patients at a higher risk of chemotherapy-induced toxicity when widely distributed drug combinations such as CMF are used, and warrants further study with other commonly used drugs or drug regimens.

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 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 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.

Measurement of total body nitrogen (TBN) levels in patients receiving adjuvant chemotherapy for breast cancer

Measurement of total body nitrogen (TBN) levels in patients receiving adjuvant chemotherapy for breast cancer

Is measurement of total body nitrogen (TBN) a useful predictor of chemotherapy ( [formula omitted]) toxicity in breast cancer?

Is measurement of total body nitrogen (TBN) a useful predictor of chemotherapy ( [formula omitted]) toxicity in breast cancer?

Dialysis adequacy and nutrition determine prognosis in continuous ambulatory peritoneal dialysis patients.

Peritoneal membrane function was assessed in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) using parameters derived from urea kinetic modeling and the peritoneal equilibration test (PET). Their relationships with other nutritional markers and overall morbidity were determined. Data regarding the patients' nutritional status as determined by total body nitrogen (TBN) measurements, hospital admissions, and infectious complications within the last 12 months were reviewed. Total dialysate clearance (Kt/V) delivered was highly dependent on residual renal function (P < 0.0001). Kt/V derived from peritoneal clearance diminished with increasing age (P < 0.05). A higher delivered total Kt/V was associated with higher normalized protein catabolic rates (P < 0.002), which in turn were associated with improved TBN (P < 0.05). Hospital admissions decreased with improved normalized protein catabolic rates (P < 0.05), and higher serum albumin and total protein levels (P < 0.01 and P < 0.002, respectively). Infectious complications correlated positively with time on dialysis (P < 0.01), and correlated negatively with TBN measurements (P = 0.05). No correlations were found between infectious complications and serum albumin level or peritoneal protein loss. However, the total duration of hospitalization was shortened with higher serum albumin and total protein levels (P < 0.0001 and P < 0.002, respectively). Although Kt/V determinations did not correlate with clearances determined by the PET, the PET-determined creatinine transport rate correlated with TBN (P < 0.05) but not with infectious complications. In conclusion, nutritional parameters correlate with outcome on continuous ambulatory peritoneal dialysis. An integral relationship exists between nutritional status and dialysis delivery, which is best assessed by urea kinetic modeling.

Assessment of the nutritional state of dialysis patients.

The importance of the nutritional state of our dialysis patients has been stressed for many years. Although the calculation of the protein catabolic rate has become common practice in many dialysis units, there are several problems with this measurement. In addition, the serum albumin level is subject to multiple influences making its interpretation in individual patients difficult. This paper examines a different approach to nutritional assessment-that of using longer term measures of nutrition. Several techniques for measuring body composition are explored and their use in end-stage renal disease (ESRD) examined. Total body nitrogen measurement is a gold standard technique which has been validated in renal patients, unfortunately it is not widely available. Of the alternatives, dual energy X-ray absorptiometry scanning for assessment of fat-free mass appears to be the best technique with the narrowest limits of agreement compared to gold standard techniques. Whilst bioelectrical impedance is reasonable for body water assessment, it is not reliable in ESRD patients for lean-body mass estimation.

Nutritional Assessment in the Critically Ill

Although many of the measurements and techniques outlined in this article may be epidemiologically useful and correlate with morbidity and mortality, no single indicator is of consistent value in the nutritional assessment of critically ill patients. Measurements such as anthropometrics, total body fat estimation, or delayed hypersensitivity skin testing either are liable to non-nutritional influences or lack accuracy and precision in individual patients. Plasma concentrations of hepatic proteins are affected significantly by the patient's underlying disease state and therapeutic interventions and therefore lack specificity. Although the measurement of these proteins is of little value in the initial nutritional assessment of the critically ill, serial measurement, particularly of plasma pre-albumin, may be useful in monitoring the response to nutritional support. Nitrogen balance is a widely used and valuable nutritional indicator in the critically ill. Direct measurement of urine nitrogen is the preferred test, although nitrogen excretion often is derived from 24-hour urine urea measurement, an inexpensive and easy procedure, but one that is less accurate. More accurate techniques of assessing change in nutritional status, such as IVNAA of total body nitrogen or isotopic measurement of exchangeable potassium or sodium, are more expensive, less available, unsuitable for repeated analyses, and less feasible in severely ill patients. Total body nitrogen measured using IVNAA and total-body potassium, however, are the most accurate ways of measuring body composition in the presence of large amounts of edema fluid. The application of body composition measurements to patient care remains poorly defined because of the many problems encountered with the various techniques, including cost, availability, and radiation exposure. Improved, more sensitive and, preferably, bedside methods for the measurement of body composition are needed. It is of paramount importance that these methods are validated extensively in the critically ill as well as in more stable patients, not only in terms of analytical accuracy, but also to define the point at which altered body composition influences clinical outcome. The biochemical measurement of levels of vitamins, minerals, and trace elements is invaluable in demonstrating specific deficiencies associated with disease and assessing whether long-term nutritional support is adequate. Such measurements rarely are necessary to make the initial clinical decision to give nutritional support, however. The most widely used measures of nutritional state are nitrogen balance and secretory protein concentrations, and these indices improve when sick patients recover.(ABSTRACT TRUNCATED AT 400 WORDS)

Total body nitrogen as a prognostic marker in maintenance dialysis.

In order to assess long-term nutritional adequacy, 154 patients on maintenance dialysis (78 on hemodialysis (HD), 76 on continuous ambulatory peritoneal dialysis (CAPD)) underwent measurement of total body nitrogen (TBN) with concurrent recording of dietary history, anthropometrics, and serum albumin. Seventy-one patients were reassessed 23.3 +/- 2.2 (5 to 76) months later. In cross-sectional analyses, anthropometric measurements and dietary intake remained stable over time in all patients. However, a significant fall in TBN occurred in the HD population with increasing time on dialysis (P < 0.05). In the prospective analyses, CAPD patients (N = 26) had a significant increase in TBN (P < 0.02). In contrast, longitudinal measurements of TBN in HD patients (N = 36) tended to fall but did not reach significance (P = 0.18). TBN correlated with total caloric intake estimated from the dietary history (P < 0.05), but not with estimated protein intake. During follow-up, 38 patients died. These patients were older (P < 0.05), and in the CAPD population, they had been on dialysis for a longer time (P < 0.05). Those who died had a lower TBN expressed both as grams per kilogram lean body mass (P < 0.005) and as the nitrogen index (P < 0.05). The probability of death within 12 months in the patients with a nitrogen index (ratio of the measured nitrogen to the predicted nitrogen for a sex-, age-, and height-matched control) less than 80% of the predicted normal value was 48%. The relative risk of death in this population was 4.1.(ABSTRACT TRUNCATED AT 250 WORDS)

Hydrogen background in total body nitrogen estimations

Total body nitrogen (TBN) is measured by in vivo, prompt gamma neutron capture analysis. Usually the background under the nitrogen peak is subtracted before calculating TBN from the ratio of nitrogen counts (at 10.8 MeV) to hydrogen counts (at 2.2 MeV). The hydrogen acts as an internal standard. The background under the hydrogen peak is usually ignored. The current study was undertaken to measure the variation of the hydrogen background (HB) in patients of different sizes and to determine whether the accuracy of TBN measurements is improved when an HB correction is incorporated. Heavy-water(D2O) phantoms were used to quantify patient HB. D2O simulates patient neutron scattering without contributing to the hydrogen peak. Equations were developed to predict HB in patient measurements. HB was found to vary from 9% of total counts for a 99 kg subject to 19% for a 7 kg infant. It was demonstrated that the accuracy of TBN measurements is improved for child-sized anthropometric phantoms of known composition when an HB correction is incorporated.

Choice of detectors for in vivo elemental analysis by counting natural and neutron-induced gamma rays for medical applications

Body fat is measured by detecting C and O in vivo through fast neutron inelastic scattering. A sealed DT neutron generator is used for the pulsed (4–10 kHz) production of fast neutrons. Carbon and oxygen are detected by counting the 4.44 and 6.13 MeV gamma rays resulting from the inelastic scattering of the fast neutrons from 12C and 16O. Large Bi 4Ge 3O 12 (BGO) crystal detectors (127 × 76 mm) are used for the gamma ray detection during the 10 μs neutron burst. BGO detectors improved the signal to background ratio for the carbon detection by a factor of six compared to 152 × 152 mm NaI (Tl) detectors. Exposure to scattered neutrons did not affect the gain stability of the BGOs. Thermal neutrons from a moderated 238PuBe source are used for the measurement of total body nitrogen (and thus protein). The resulting high energy prompt gamma rays from nitrogen (10.83 MeV) are detected simultaneously with the irradiation. BGO detectors have superior stability operating in an environment of variable neutron exposure and high counting rates. However, the presence of neutrons creates a 10.2 MeV gamma ray peak from 73Ge in the BGO detector which interferes with the nitrogen peak. Whole body gamma ray counters, consisting of NaI(Tl) crystal detectors in a shielded room, are used to measure the natural radioactivity of the body due to 40K. They are also used to measure body Ca, P, Na and Cl, following total body exposure to thermal neutrons.

Changes in body composition following a very low calorie diet.

The efficacy of a diet can be determined in part by the weight lost and in particular by the composition of that weight. This need to be specific about changes occurring in the body composition, and in particular the protein content of the fat-free component, has prompted attempts to measure protein changes by recording nitrogen intake and loss. However, accurate results are not easy to achieve because of unmeasured losses such as those through the skin and body secretions. In recent years the direct measurement of total body nitrogen (TBN), and hence protein (TBProt), by in vivo neutron activation analysis (IVNAA) has enabled accurate measurements to be undertaken. As compared with traditional methods for evaluating the fat-free mass (FFM), the IVNAA measurements provide a more comprehensive assessment of body composition. The present study reports the use of IVNAA to measure the changes in body composition arising from adherence to a very low calorie diet (VLCD) and extends the preliminary results reported previously1.

A correction for total body hydrogen used as an internal standard in the measurement of total body protein by prompt gamma in vivo neutron activation analysis

Total body protein (TBP) has been estimated from the measurement of total body nitrogen (TBN) by prompt gamma in vivo neutron activation analysis (IVNAA) for approximately 20 years. The use of total body hydrogen (TBH) as an internal standard for the measurement of total body nitrogen (TBN) for protein (TBP) by prompt gamma in vivo neutron activation analysis (IVNAA) was first proposed by Vartsky et al. (1979). The use of hydrogen as an internal standard has a threefold advantage. Firstly, the observed N/H ratio is not greatly dependent on body size since gamma rays at different energies (10.8 MeV and 2.223 MeV) are attenuated to a similar extent, and both elements are similarly distributed with depth to capture thermalized neutrons. Secondly, the whole body N/H ratio can be determined by irradiating a representative portion of the body (torso, arms and thighs which include between 80 and 90% of body mass), thereby minimizing risk to radiosensitive tissues such as the eyes. Thirdly, the method corrects for any slight variations in total neutron fluence between measurements.

Nitrogen deposition in malnourished children with cystic fibrosis

To determine the protein nutritional status of 21 malnourished children with cystic fibrosis (CF), total body nitrogen (TBN) was measured and the results were compared with 21 control subjects. CF patients demonstrated a lower TBN (P less than 0.001). When matched for height (n = 10) or bone age (n = 13), the CF patients still had a depressed TBN/height or TBN/lean body mass (P less than 0.05). To assess nitrogen deposition during nutritional rehabilitation, repeat TBN measurements were performed on the 21 CF patients. Nitrogen deposition ranged from -230 to 550 g/y and correlated with weight velocity (r = 0.78, P less than 0.001). Increased nitrogen deposition (greater than 150 g/y) was generally associated with normal height gain (height velocity SD score greater than -2.00) and weight gain (greater than 2.0 kg/y). Decreased nitrogen deposition was associated with poor weight gain but did not preclude normal linear growth. These data suggest an important role for TBN estimations in defining protein nutritional status in children and indicate that skeletal growth can continue in the presence of minimal nitrogen deposition.