Joan E. Harrison

Metabolic Bone Disease in Patients Receiving Long-Term Total Parenteral Nutrition

We have prospectively investigated calcium and bone metabolism in 16 patients receiving total parenteral nutrition for periods ranging from 7 to 89 months. In 12 patients, bone biopsies at 6 to 73 months after the start of parenteral nutrition showed osteomalacia. Plasma 25-hydroxyvitamin D levels were normal in all patients. Seven persons developed hypercalcemia, and 10 had hypercalciuria with a negative calcium balance. Serum phosphorus was normal and plasma parathyroid hormone level, normal or decreased. Three patients with the severest form of the disease had vitamin D withdrawn from their solutions. Subsequently, urinary calcium decreased, and serum calcium became normal; two persons reverted to a positive calcium balance. Thus, patients receiving total parenteral nutrition may develop metabolic bone disease characterized by osteomalacia, hypercalcemia, hypercalciuria, and a negative calcium balance. This may be caused by both defective mineralization and increased bone resorption induced by vitamin D, its metabolites, or another unrecognized factor.

Changes in body composition in patients with small-cell lung cancer. The effect of total parenteral nutrition as an adjunct to chemotherapy.

y composition was studied in 31 patients receiving chemotherapy for small-cell lung cancer. Patients were randomly assigned to receive either 4 weeks of total parenteral nutrition (study group) or to continue a self-regulated oral diet (control group). The relationship between height and total body nitrogen was altered initially for patients who had lost more than 5% of body weight. During the 4 weeks of parenteral nutrition, body weight, total body fat, and total body potassium, but not total body nitrogen, increased significantly in the study group (p less than 0.001). However, after parenteral nutrition was stopped, body weight and potassium levels in the study group fell significantly and to the same extent as in the control group. Nitrogen levels showed an overall fall in the 32 weeks of observation for both groups. After the period of parenteral nutrition, the decrease in body fat was significantly greater in the control group than in the study group (p less than 0.05). Thus, parenteral nutrition increased body fat and total body potassium, but not total body nitrogen.

Total body bone mineral and lean body mass by dual-photon absorptiometry: II. Comparison with total body calcium by neutron activation analysis

SummaryTotal body bone mineral (TBBM) was measured in vivo using dual-photon absorptiometry (DPA) in 10 subjects. The total body calcium (TBCa) was measured in the same subjects using neutron activation analysis. The correlation between the two methods was very high (r>0.99) and the standard error of estimate was low. The TBCa relative to TBBM was about 39%. The two noninvasive methods provided nearly identical indications of skeletal mass, but the radiation exposure with DPA was 500 to 5000 times smaller (0.6 mrem vs 300 to 3000 mrem). The radius shaft bone mineral content was highly correlated with the TBBM (0.97) and the TBCa (0.98) and could be used to estimate the latter variables with errors (1 SEE) of 9% and 6%, respectively.

A Possible Role of Vitamin D in the Genesis of Parenteral-Nutrition-Induced Metabolic Bone Disease

Patients receiving long term parenteral nutrition may develop metabolic bone disease. In all 11 patients studied, histologic studies of bone showed excessive unmineralized bone tissue despite normal plasma 25-hydroxyvitamin D levels. Three patients also had bone pain and fractures and severe urinary loss of calcium and phosphate. Withdrawal of vitamin D from parenteral nutrition solutions was associated with improved histologic findings of bone in all patients, shown by a decrease in osteoid tissue and an increase in tetracycline uptake. In the three patients with symptoms, bone pain subsided, fractures healed, and urinary loss of calcium and phosphate decreased. Thus, vitamin D may be a factor in the genesis of parenteral nutrition-induced metabolic bone disease.

Critical evaluation of the role of clinical assessment and body composition studies in patients with malnutrition and after total parenteral nutrition.

verely malnourished patient, the exact rec-ognition of early and subtle malnutrition isnot as simple. Furthermore, the results ofsuch marginal deficiency are not clearlyknown. Since the recognition and knowledgeof the effects of early malnutrition are bothimportant in defining the need for nutritionalsupport, several investigators have attemptedto study this area. They have related a varietyof parameters of anthropometry and bio-chemistry

In vivo determination of nitrogen using Pu-Be sources

A mehtod of measuring body nitrogen by neutron capture gamma analysis is described. The neutron flux is provided by four collimated 5 Ci Pu-Be sources, placed to give a bilateral irradiation of the subject. The 10-83 MeV thermal neutron capture gamma rays from 14N are detected by two heavily shielded 5 in X 4 in NaI(Tl) detectors. Results indicate a reproducibility +/-3% (1 SD) for a 10 min irradiation of the chest area, while giving a radiation dose equivalent of 50 mREM.

Effect of long-term thiazide therapy on intestinal calcium absorption in patients with recurrent renal calculi

Abstract Recurrent calcium-containing renal calculi are a common and poorly understood problem. Thiazide diuretics decrease urinary calcium excretion but their effect on other parameters of calcium metabolism is not established. The purpose of this study was to determine the effect of chronic administration of thiazide diuretics on intestinal calcium absorption, skeletal calcium turnover, and urinary calcium excretion, and to use this information to attempt to clarify the pathogenesis of idiopathic hypercalciuria. Forty-one patients with recurrent calcium-containing renal calculi were studied; 73% had hypercalciuria, 44% had increased intestinal absorption, and 7% had increased bone turnover. Thiazide diuretics given to 22 patients for 3–16 mo resulted in a consistent reduction in urinary calcium excretion, while calcium absorption was unchanged (

Aluminum toxicity to the brain

The association between elevated brain aluminum levels and Alzheimers disease (AD) is examined and critically reviewed. We found elevated aluminum levels in the brains of patients with AD (greater than 4 micrograms/g dry wt.) compared with normal subjects (approximately 1.5 micrograms/g dry wt.). Nine laboratories from different geographical regions have confirmed this finding. Two laboratories did not find any differences between AD and control brains. This discrepancy is traced to differences in sample sizes used for the aluminum assay and the sample selection criteria. It is found that it is essential to use small sizes (approximately 10 mg dry wt.) and to ensure that control brains do not contain neurofibrillary tangles (NFT) and that AD brains do. The exact pathogenic role of aluminum in AD is, as yet, unclear. It is the only element (other than calcium, which non-specifically accumulates at all degenerating tissue sites) that is found in elevated concentrations in NFTs. It is found elevated at four loci in the brain, i.e. the DNA-containing structures of the nucleus, the protein moities of NFTs, the amyloid cores of senile plaques and cerebral ferritin. The evidence thus far indicates that aluminum is toxic to the brain and it is probable that it has a pathogenic role in Alzheimers disease.

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.