Some aspects of body composition in cancer.

Changes in body composition, in cancer as in benign disease, simple starvation or overfeeding, show the integrated effect of a period of metabolic imbalance. Therefore, accurate measurements of body composition can help to elucidate the mechanisms that bring about the imbalance. Techniques of measurement that depend for their accuracy on the constancy of some property of the entire fat-free tissues are unlikely to give accurate results in obese or wasted patients. It is more informative, and more accurate, to measure fat, water, protein and mineral separately, and at present this is best done by dilution of labelled water and multi-element in vivo neutron activation analysis. Changes should be determined by sequential measurement wherever possible; otherwise results must be compared with 'normal' values found by measuring healthy subjects, correcting if necessary for differences in age and stature between patients and healthy subjects.

Influence of energy source upon body composition in patients receiving intravenous nutrition.

The influence of energy substrate upon body composition was investigated by measuring changes in the body composition of 24 patients who received intravenous nutrition for 2 weeks. The patients were randomly allocated to two groups. Twelve patients (the "glucose group") received all 'nonprotein' calories as glucose, the remaining 12 (the "fat-glucose group") received 60% of 'nonprotein' calories as fat emulsion (Intralipid). Amino acids (FreAmine II) were supplied to give a calorie/nitrogen ratio of 150:1. Total calories were supplied at a rate of 1.4 times the measured resting energy expenditure of each patient. Body composition was measured using routine anthropometric techniques and in vivo neutron activation analysis. Significant increases in body fat and total body potassium (TBK) were recorded in the glucose group, but there was no significant change in total body water (TBW) or total body nitrogen (TBN) in either group. The initial value of the ratio of TBK:TBW had a significant negative correlation with the change of TBK in both groups, and with the change of TBN in the glucose group. The study demonstrates the importance of considering nutritional status when analyzing the effects of intravenous nutrition. Glucose as the sole source of calories induced an increase in body potassium independent of protein synthesis; this effect was not observed in patients who received 60% of their energy supply as lipid emulsion.

Changes in the absorption of bile acids after total colectomy in patients with an ileostomy or pouch-anal anastomosis.

Bile acid absorption was investigated using 75Se Taurohomocholate (SeHCAT) in controls and patients who had undergone total colectomy with either conventional ileostomy or pouch-anal anastomosis for ulcerative colitis or adenomatous polyposis. Whole-body retention of SeHCAT after 168 hours was greater in the controls than the patients who had undergone colectomy (P less than .05). Retention of SeHCAT did not differ significantly between patients with an ileostomy and patients with pouch-anal anastomosis, but patients with an ileostomy and ileal resection of more than 20 cm retained less SeHCAT than patients with a pouch-anal anastomosis (P less than .01). Analysis of fecal bile acids from ileostomies and pouches showed that bacterial metabolism of primary conjugated bile acids was greater in patients with a pouch. It was concluded that bile acid absorption was not significantly impaired by construction of a pouch compared with conventional ileostomy, but bacterial metabolism of bile acids was greater in the pouches.

Isotope computed tomography using cone-beam geometry: a comparison of two reconstruction algorithms.

A CT scanner has been constructed specifically to determine the three-dimensional distribution of bone mineral in the medullary cavities of the radius, ulna and femur. A source of x-rays (153Gd) and a multiwire proportional counter (MWPC) are mounted at opposite ends of a diameter of an annular mounting. The limb is placed on the axis of rotation of the annulus and a series of two-dimensional transmission projections are obtained at equal angular spacings over 360 degrees. The distribution of bone mineral is reconstructed from the projections either by the method of maximum entropy (ME) or by convolution and back projection (CBP). These two methods have been evaluated by reconstructing a single slice of a phantom, representing the forearm, from projections simulated by computer. With a clinically acceptable exposure time, the mean medullary densities of the ulna and radius were determined with systematic errors of less than 3.5% (ME) and 11% (CBP), although for the latter method of reconstruction the systematic error was reduced to less than 2% by increasing the number of views. The mean medullary densities of the ulna and radius were determined with precisions better than 2.5% (ME) and 3.5% (CBP).

Body composition of fasting obese patients measured by in vivo neutron activation analysis and isotopic dilution.

The masses of fat, water, protein and minerals in ten obese patients (seven women and three men) have been measured, by in vivo neutron activation analysis and isotopic dilution, before and after four weeks of starvation. Mass of skeletal muscle was estimated from measured total body potassium (TBK) and nitrogen (TBN). Before starvation the patients weighed, on average, 56.5 kg more than predicted from sex, age and height. The composition of their excess tissue was consistent with that of adipose tissue. During starvation the patients lost, on average, 12.1 kg of tissue containing more water and potassium than adipose tissue. Regression analysis of the measured changes in potassium and protein suggested that approximately 230 mmol of potassium was lost independently of protein, the remainder being lost with 'non-muscle' fat-free tissue. Because some potassium was lost without protein, the change in muscle mass calculated from the changes in TBK and TBN overestimated the true mass of muscle lost. After starvation the patients still had 44.5 kg of excess tissue. Their composition was consistent with an excess of adipose tissue and a deficit of potassium.

A controlled trial of nandrolone decanoate in the treatment of rheumatoid arthritis in postmenopausal women.

To determine whether an anabolic steroid had any benefit in the treatment of rheumatoid arthritis 47 patients entered a parallel group study. Twenty four received nandrolone decanoate 50 mg intramuscularly every third week for two years and 23 patients received no anabolic steroids. Other therapy was unaltered. Patients attended for clinical and biochemical assessments as well as the objective assessments of elementary body composition by in vivo neutron activation analysis and measurement of the mineral content of the distal femur by single photon absorptiometry on five occasions. A modest clinical deterioration (except for grip strength) was seen in both groups. No significant changes in calcium or alkaline phosphatase were seen. There was no significant change in total body calcium, total body phosphorus, body weight, or bone index/bone width measurements in either group. Significant increases occurred in total body nitrogen, total body potassium, haemoglobin, and packed cell volume (by six months) in the group treated with nandrolone decanoate. Comparison of 10 patients in the group treated with nandrolone decanoate also receiving oral steroid therapy with 14 patients in this group not receiving oral steroid therapy showed no significant differences. The main side effect of nandrolone decanoate was hoarseness. No radiological changes were seen. Nandrolone decanoate, in a dose that produces a significant anabolic effect, has no demonstrable action on bone metabolism in rheumatoid arthritis but may improve the chronic anaemia by six months.

Body composition in malignant disease.

It has been suggested that adaptation to starvation may be impaired in patients with malignant disease and that this may contribute to the development of cancer cachexia. We have investigated this by comparing the body composition, as well as the tissue composition of weight loss, of a group of 49 patients with gastrointestinal carcinomas and 91 patients with benign gastrointestinal disease all of whom had sustained a weight loss greater than 10% of their recalled pre-illness weight. Total body protein was calculated from total body nitrogen measured by in vivo neutron activation analysis which also provided absolute values of sodium, chlorine, phosphorus, and calcium. The masses of muscle and nonmuscle protein were estimated using a validated compartmental analysis. Total body fat was derived using anthropometry. Total body water was estimated from the difference between body weight and the sum of body protein, fat, and minerals. The loss of body weight incurred by patients with both benign and malignant disease was primarily muscle mass and body fat. Both groups of patients retained nonmuscle protein. All patients manifested, with increasing weight loss, a progressive loss of muscle protein, fat, and water, which must represent the tissue composition of weight loss. No significant differences between patients with benign or malignant disease were demonstrated for any of the body composition parameters measured. The results of this study do not support the hypothesis that adaptation to starvation in patients with cancer is in anyway different from that which occurs in patients with benign disease.

Tomographic reconstruction from experimentally obtained cone-beam projections.

Direct reconstruction in three dimensions for two-dimensional projection data has been achieved by cone-beam reconstruction techniques. In this paper explicit formulas for a cone-beam convolution and back-projection reconstruction algorithm are given in a form which can be easily coded for a computer. The algorithm is justified by analyzing tomographic reconstructions of a uniformly attenuating sphere from simulated noisy projection data. A particular feature of this algorithm is the use of a one-dimensional rather than two-dimensional convolution function, greatly speeding up the reconstruction. The technique is applicable however large the cone angle of data capture and correctly reduces to the pure fan-beam reconstruction technique in the central section of the cone. The method has been applied to data captured on a cone-beam CT scanner designed for bone mineral densitometry.

Body composition in ileostomy patients with and without ileal resection.

Body composition was measured in 24 patients who had previously undergone proctocolectomy and ileostomy. One group (control group) had undergone resection of only small amounts of terminal ileum (median 4 cm), the other group of patients (resected group) had undergone resection of greater lengths of small bowel (median 54 cm). These values of body composition were then compared with predicted values in normal subjects. Proctocolectomy and ileostomy without ileal resection did not significantly affect body weight, or the body contents of fat or water, but led to a reduction in total body nitrogen and total body potassium, suggesting a reduction in fat free mass. A modest resection of the terminal ileum undertaken during the course of proctocolectomy decreased body weight largely because of a reduction in body fat. None of the ileostomy patients was found to be dehydrated.

Estimating the composition of tissue gained or lost from measurements of elementary body composition.

Studies of relationships between changes in body constituents resulting from disease or treatment can, in principle, give information about the composition of the tissues gained or lost. Frequently, however, the random errors of measurement are of similar magnitude to the changes measured, so that standard statistical methods such as linear regression analysis give biased estimates of the parameters in the relationships. Possible ways of obtaining better estimates are discussed and models suitable for two types of experiment are described. In the first, patients are measured before and after the changes; in the second, patients are measured only after the changes have occurred and their results compared with those for a group of control subjects assumed to be representative of the patients before they became ill. The models have been used to analyse losses of total body nitrogen and potassium as a result of surgery and of disease. The results suggest that patients who underwent surgical operation lost 1.7 mmol K per g N. Those who suffered from disease lost 2.0 mmol K per g N, but also lost, on average, 234 mmol K independently of N. Conventional linear regression analysis would have led to very different conclusions, emphasising the importance of applying appropriate models to the analysis of such data.

Mass and composition of the fat-free tissues of patients with weight-loss.

An estimate of the mass of fat-free tissue in the body can be calculated from body weight and skinfold thickness; this estimate is called the 'fat-free mass'. Total body potassium and nitrogen are alternative estimates. Factor analysis of data for healthy subjects has defined relationships between the true values of these three quantities and estimated the random component of the variance of each, i.e. the component independent of variations in the mass of fat-free tissue. The results indicated that all three were reliable measures of the mass of fat-free tissue. However, it is not known whether these findings are valid for patients who have lost weight. We have measured the same three quantities in 104 wasted patients with heart disease or disorders of the gastrointestinal tract. The patients' mean values were significantly less than corresponding values for healthy volunteers. The patients had a mean ratio of total body nitrogen to fat-free mass similar to that of healthy subjects, but lower mean ratios of potassium to fat-free mass and nitrogen. These findings suggest that the potassium content of the patients' fat-free tissues was abnormally low. Factor analysis of the patients' data gave relationships between the true values of the three quantities similar to those for healthy subjects; however, total body potassium was 100-300 mmol lower in patients than in healthy subjects with the same fat-free mass or total body nitrogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of short-term changes in the fat content of the body: a comparison of three methods in patients receiving intravenous nutrition.

Three methods of measuring changes in body fat were compared in seventeen patients undergoing a 2-week course of intravenous nutrition. Patients received all nutrition intravenously at a steady rate of infusion, calculated to supply energy at a rate equal to 1.5 times the resting metabolic expenditure measured before feeding. Fat change was estimated from measurements of skinfold thickness, by isotopic methods (neutron-activation analysis and dilution of tritiated water) and by daily analysis of expired gases. The mean (with 1 SEM) gain in fat over the 2-week period was 1.14 (0.30) kg for skinfold measurement, 0.53 (0.62) kg for isotopic determination and 1.29 (0.22) kg for expired-gas analysis. There were no significant differences between the mean gains in fat measured by the three methods. The results show that expired-gas analysis is the most sensitive technique, measuring change in fat content with an estimated precision of 0.26 kg. The isotopic method is less sensitive, with a precision of 2.38 kg, but provides a detailed description of body composition. In contrast to these highly-specialized techniques, both of which have limited application, the simple technique of measurement of skinfolds occupies an intermediate position of sensitivity, with a precision for measuring change in fat content of 0.85 kg, and also has the potential to measure total body fat content.

Multi-element analysis of the obese subject by in vivo neutron activation analysis.

The Leeds facility for in vivo neutron activation analysis has been modified and calibrated for the simultaneous measurement of nitrogen, potassium, sodium, chlorine, phosphorus and calcium in obese patients weighing up to 210 kg. The effects of body size and shape were incorporated into the calibration by measuring 14 anthropomorphic phantoms of known composition representing individual patients being treated for obesity. The phantoms were constructed from tissue substitutes representing lean, skeletal and adipose tissues, arranged to simulate the distributions of the corresponding tissues within the patients, as visualised by CT scanning. The precision of the method, determined by measuring a single phantom ten times over a period of ten weeks, is between two and three per cent for all elements except calcium, for which it is 11.3%. Accuracy is estimated to be similar to precision. The procedure has been used to study changes in body composition of patients undergoing therapeutic starvation.

Electrolyte metabolism in patients with periodic affective disorders during treatment with rubidium.

Five patients suffering from periodic affective disorders with short mood-cycles were treated with rubidium chloride, producing peak erythrocyte concentrations between 9 and 13 mmol/l. Loading with rubidium was associated with decreased total body potassium, but red-cell potassium was unchanged. Regular mood-cycling was disturbed, together with the associated body-weight changes. There was a slight extracellular "metabolic" acidosis. Electrolyte concentrations fluctuate abnormally in these patients, and two muscle biopsy specimens had very low potassium contents.

Estimating total body calcium from peripheral bone measurements.

In a heterogeneous group of 12 male and 30 female patients, total body calcium (TBCa) was measured by neutron activation analysis, and bone mineral content of the distal femur and six regions of the distal radius and ulna were measured by photon absorptiometry. TBCa was an average of 71 g (9%) lower than normal in the females and 119 g (11%) lower than normal in the males. Of the forearm measurements, those of the radial shaft provided the best estimate of TBCa with a standard error of estimation (SEE) of 88 g (14% of the mean value) for female patients alone, and 113 g (16%) for the whole group. The measurement on the femur provided a better estimate with SEE 80 g (13%) for female patients and 90 g (13%) for the whole group. These SEE are comparable with the variability in TBCa between normal subjects, which has a coefficient of variation of the order of 20% in both sexes. A slightly better estimate of TBCa can be obtained by using a multiple regression equation involving both the femur and radial shaft measurements with a SEE of 74 g (12%) for female patients and 81 g (11%) for the whole group. The correlation between the estimated deficit of TBCa and the estimated deficit of bone mineral from the forearm and the femur has been calculated.

The feasibility of measuring total body carbon by counting neutron inelastic scatter gamma rays.

A technique is examined for measuring the mass of carbon of both ambulatory and non-ambulatory subjects. The method is based upon the detection of the 4.43 MeV gamma rays emitted from carbon nuclei when the body is irradiated with fast neutrons. The supine subject is irradiated laterally by a horizontal collimated beam of 14 MeV neutrons and the emitted gamma rays are counted by a shielded NaI(Tl) detector placed underneath the subject. The method has been calibrated for all sizes of subjects from 30 to 90 kg and there appears to be no significant interference from the other bulk elements of the body. Body carbon has been measured in six normal volunteers; body nitrogen was also determined by measuring the 13N induced in each subject in a second irradiation. Body fat was estimated from the measured carbon and nitrogen, and the values compared with those derived from skinfold thicknesses. The technique is proposed as a method of estimating long-term energy expenditure.