K. G. McNeill

A nitrogen index — total body protein normalized for body size — for diagnosis of protein status in health and disease

Abstract Total body nitrogen (TBN) was measured in 121 volunteers. TBN depends on body size, with the best simple relationship being TBN α (HAS) 2.6 for both men and women, where HAS is a mean of height and arm span. This relationship was used as a predictor of normal TBN. Weight and total body potassium (TBK) were considered for improving normalization, but rejected. Five patients with anorexia nervosa had only 71% of predicted nitrogen. Twelve patients with malabsorption syndrome initially had 68% of normal, but after a year of total parenteral nutrition this increased to 95%. On the other hand, 14 patients with renal failure initially had near normal nitrogen but after a year on continuous ambulatory peritoneal dialysis, nitrogen fell by 20%. TBN, when normalized for body size, provides a reliable index of protein status in clinical investigation and cannot be accurately predicted by weight or TBK.

Measurement of fluoride in bone

Abstract The fluorine concentration in bone biopsy samples was measured by neutron activation analysis. The fluorine content was expressed in terms of the calcium content. Samples were irradiated in a reactor to induce the 19 F (n, γ) 20 F and 48 Ca (n, γ) 49 Ca reactions and after rapid transport from the reactor the resulting activities were measured with a Ge(Li) detector. Reproducibility was better than 10% for the F/Ca ratio. The detection limit for F is 50 μg. This nondestructive technique will be used to assess the effect of fluoride therapy on bone metabolism of patients with idiopathic osteoporosis.

Increased bone mineral content in young adults with familial hypophosphatemic vitamin D refactory rickets

Seven adults with familial hypophosphatemia have been investigated by histologic and radiographic examination of bone, and estimates of bone mineral status by in vivo neutron activation analysis (IVNAA). Histological examination showed severe osteomalacia and osteosclerosis in all cases. Radiography showed skeletal deformities and other sequelae of severe rickets of childhood in five of the seven cases, with, in addition, thickened well-mineralized bones; the other two showed normal radiographs. IVNAA measurements showed that the first five had greater than normal bone calcium and that the other two had normal values. Thus, in all cases there is a greater than normal total bone tissue (osteoid and mineralized bone together). The quantitative body calcium measurements show clearly that osteosclerosis occurs in familial hypophosphatemia, confirming the opinions based on histological and radiological data. Although there has been occasional reference to this sclerosis in the literature, up to the present it has received little attention.

Calcium Kinetic Studies in Patients with Malabsorption Syndrome

In a group of 12 patients with steatorrhea secondary to various etiologies, defective calcium absorption and negative calcium balance occurred in all patients with biochemical osteomalacia. Losses of body calcium resulted from obligatory endogenous fecal losses. High endogenous fecal calcium values appeared to be due to increased digestive juice secretions as well as defective reabsorption. Bone calcium turnover in osteomalacia varied from below to well above the normal range in agreement with reported data on bone biopsy studies. Markedly elevated bone calcium accretion rates were found in idiopathic steatorrhea alone and were associated with advanced bone disease.

In vivo analysis of bone fluoride content via NMR.

In vivo free induction decay signals have been detected from the fluoride ion (F) content of human finger bones by a 27 MHz pulsed single-coil nuclear magnetic resonance (NMR) spectrometer. The intensity of these dipolar-broadened NMR signals can be used to estimate the F content of the middle phalanx of the index finger. This NMR procedure is the first non-invasive method capable of monitoring bone F contents. The preliminary results we report were obtained from patients known by previous biopsies to have relatively high bone F concentrations in their pelvis. This new monitoring technique does not yet have adequate sensitivity or accuracy for routine clinical use. As a research technique, it has applications to the diagnosis of fluorosis (both industrial and endemic) as well as renal osteodystrophy, and to the establishment of optimal NaF does for the treatment of osteoporosis.

Clinical Studies of Total Body Nitrogen in an Australian Hospital

The first reports of the measurement of Total Body Nitrogen (TBN) by In Vivo Neutron Activation Analysis (IVNAA) using a cyclotron date from the early 1970’s (Harvey et al., 1973). By the late 1970’s other laboratories were using the prompt gamma IVNAA technique with isotopic neutron sources (Mernagh et al., 1977; Vartsky et al., 1979a). The prompt IVNAA method is a relatively simple, non-invasive test which requires approximately 20 minutes of the patient’s time. The radiation dose is minimal, and both capital and running costs are small. Clinically, Total Body Protein (TBPr) can be reliably estimated from TBN (TBPr = 6.25 × TBN). The many clinical applications of the technique are described by Wahlqvist and Marks elsewhere in this volume, and by McNeill (1988). It is therefore surprising that so few hospitals are currently using the technique.

Effect of treatment of calcium kinetics in metabolic bone disease

Abstract The effect of treatment on calcium kinetic and balance studies was investigated on six patients with osteoporosis (group A). The results were compared with data obtained from similar studies on four patients with calcium abnormalities secondary to steatorrhea and on one infant with vitamin D-dependent rickets (group B). The studies were carried out before treatment and subsequently at various periods up to 2 yr after the onset of treatment. The effect of treatment on bone calcium kinetics differed significantly between the two groups. In osteoporosis (group A), accretion rates of calcium to bone were lower as compared to pretreatment values. In contrast, in four of the five subjects of group B, accretion rates increased from pretreatment values. The results show that in osteoporosis changes in bone calcium metabolism were observed for as long as 2 yr on treatment, despite the fact that the balance data were normal at this time.

Investigation of factors which lead to the background in the measurement of nitrogen by IVNAA

A major problem in the measurement of nitrogen in the body by in vivo neutron activation analysis is the size of the background. Investigations show that random summing of gamma rays in the range 4-7 MeV is a major contributor. By direct comparison, 252Cf is shown to be a better neutron source than Pu-Be in this regard. Data are presented on the contribution to the background of water and chloride in the body.

Partial body calcium measurements on patients with renal failure

The bone calcium status of 39 patients with chronic renal failure on hemodialysis has been measured by in vivo neutron activation analysis (IVNAA) and reported in terms of a calcium bone index (CaBl) which relates the calcium in a patient to that in a normal person of the same height. In 20 of the 39 cases sequential measurements were made over periods of up to 40 mo. The results are compared with data obtained by radiology and by histological examination of bone biopsies. CaBl values varied from below normal to, in one case, above the range of normal. Many of the higher values were associated with demonstrable osteosclerosis. As found in previous work here with IVNAA, significantly low values of CaBl were associated with vertebral deformities; however, some patients with deformity had normal CaBl values, indicating that these had both local mineral loss (resulting in fracture) and osteosclerosis. Taken all together, the data suggest that more than half the patients have osteosclerosis. Sequential data showed no uniform response to treatment.

Effects of body thickness on in vivo neutron activation analysis

Abstract In the procedure of in vivo neutron activation analysis for calcium and other elements, the thickness of the body affects both neutron flux distribution in the body and self-absorption of gamma rays emitted by the body. Measurements have been carried out to find the effects of these factors individually and also when combined. With the PuBe neutron source and NaI detector arrangements used at Toronto for activation analysis of the trunk, the combined changes in calcium counts are about 5 per cent for each 1 cm change in the thickness of the subject.