The end-product method of measuring whole-body protein turnover: a review of published results and a comparison with those obtained by leucine infusion.

The present review summarizes the results of all published papers on whole-body protein turnover in man measured by [15N]glycine and the end-product method using both urea and ammonia. It begins with a short account of the underlying assumptions and the justification for the use of [15N]glycine. The results are then compared with those of a large sample of measurements by the 'gold standard' precursor method with continuous infusion of [13C]leucine. The pros and cons of the two methods are compared and it is suggested that there is a place for further work by the less invasive end-product method, particularly for population studies of the genetic, environmental and functional determinants of whole-body rates of protein synthesis.

Feeding the world in the new millennium.

Food production per head in the world as a whole has begun to level off in the last decade, while the world population continues to grow, risking malnutrition, perhaps even starvation, civil unrest and environmental damage. Very little more land suitable for agriculture is available, and the factors behind the 'green revolution' may not produce further increases. Genetically modified crops offer the possibility of increased yields, but also present major problems. In developing countries, where yields are well below what is theoretically possible, the best approach may be better management by small farmers through improvements in their traditional methods. Much more financial support for and research in agriculture is needed, together with more equitable distribution of existing production and an end to trade practices designed to make the rich richer.

Treatment of children with malnutrition and diarrhoea.

PIP: Researchers at the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) in Dhaka examined the effects of a standardized protocol against a nonstandardized treatment. The research focused on the management of severely malnourished children with diarrhea. The results showed a 9% mortality in the test group (standardized treatment) whereas mortality in the control group (nonstandardized treatment) was 17%. In addition, only 40% of children in the test group received intravenous infusions, compared with 70% of the controls. In this study, the nature and amount of intravenous therapy suggests that the deaths were due primarily to malnourishment. In line with this and in recognition of the fatal consequences of infection on severe protein-energy malnutrition, WHO has produced a manual on the management of this deficiency. Three conventional phases of treatment are presented in this manual, which are in accordance with the conclusions of the ICDDR,B study: to avoid intravenous therapy and the use of low-sodium rehydration solution. Priorities in the first phase are rehydration, treatment of infection, and provision of important trace elements. In the second phase, the daily requirements do not exceed 80-100 kcal/kg of energy and 1 g protein/kg. The final phase is initiated when appetite has been restored, and high-energy feeds with reasonable amounts of protein can be safely given. The comprehensive distribution of this manual in developing countries is recommended, together with proper training for doctors and nurses.^ieng

The nature and significance of nutritional adaptation.

Possible adaptations to a low protein intake are: a decrease in the obligatory nitrogen loss, which would be too small to detect in short-term studies, but would be significant over a longer term; an increase in the efficiency of protein utilization, which has been demonstrated in depleted subjects; and a decrease in lean body mass, mainly at the expense of muscle. However, we do not know the extent to which this last mechanism may really be an adaptation without significant functional loss. In the case of energy there is controversy about the extent to which the gross efficiency of muscular work can be improved. One mechanism might be an alteration in the distribution of fibre types, with a shift from fast to slow fibres. A possible way of reducing the cost of both muscular work and basal metabolism would be a reduction in the mitochondrial proton leak. Both these mechanisms are at least partially under the control of the thyroid gland, which therefore may play an important role in economizing energy expenditure.

The mysteries of nitrogen balance.

The first part of this review is concerned with the balance between N input and output as urinary urea. I start with some observations on classical biochemical studies of the operation of the urea cycle. According to Krebs, the cycle is instantaneous and automatic, as a result of the irreversibility of the first enzyme, carbamoyl-phosphate synthetase 1 (EC 6.3.5.5; CPS-I), and it should be able to handle many times the normal input to the cycle. It is now generally agreed that acetyl glutamate is a necessary co-factor for CPS-1, but not a regulator. There is abundant evidence that changes in dietary protein supply induce coordinated changes in the amounts of all five urea-cycle enzymes. How this coordination is achieved, and why it should be necessary in view of the properties of the cycle mentioned above, is unknown. At the physiological level it is not clear how a change in protein intake is translated into a change of urea cycle activity. It is very unlikely that the signal is an alteration in the plasma concentration either of total amino-N or of any single amino acid. The immediate substrates of the urea cycle are NH3 and aspartate, but there have been no measurements of their concentration in the liver in relation to urea production. Measurements of urea kinetics have shown that in many cases urea production exceeds N intake, and it is only through transfer of some of the urea produced to the colon, where it is hydrolysed to NH3, that it is possible to achieve N balance. It is beginning to look as if this process is regulated, possibly through the operation of recently discovered urea transporters in the kidney and colon. The second part of the review deals with the synthesis and breakdown of protein. The evidence on whole-body protein turnover under a variety of conditions strongly suggests that the components of turnover, including amino acid oxidation, are influenced and perhaps regulated by amino acid supply or amino acid concentration, with insulin playing an important but secondary role. Molecular biology has provided a great deal of information about the complex processes of protein synthesis and breakdown, but so far has nothing to say about how they are coordinated so that in the steady state they are equal. A simple hypothesis is proposed to fill this gap, based on the self-evident fact that for two processes to be coordinated they must have some factor in common. This common factor is the amino acid pool, which provides the substrates for synthesis and represents the products of breakdown. The review concludes that although the achievement and maintenance of N balance is a fact of life that we tend to take for granted, there are many features of it that are not understood, principally the control of urea production and excretion to match the intake, and the coordination of protein synthesis and breakdown to maintain a relatively constant lean body mass.

Regional study days. Their role within the education strategy of the TVS.

The Tissue Viability Society (TVS) Regional Study Days (RSDs) aim to bring high quality education on pressure sore prevention and wound care to a large section of health care professionals who may well not attend conferences and who often do not find the time to read articles in journals and magazines. Since 1987 over 200 RSDs have been held providing education to over 20,000 delegates. The RSDs have also contributed in the region of 50,000 Pounds to the Society's funds. The first RSDs were held in the West Country, but since that time the area has extended to include the whole of the United Kingdom. The panel of approximately 12 speakers across the country are all recognised experts in the subjects of pressure sore prevention and wound care. Attendance at RSDs is free to all NHS staff. The historical background of the RSDs is presented and the manner in which they fit into the overall strategy of the TVS to provide an educational service to all levels of health care professionals.

Enrichment in urinary ammonia and urea with hourly oral doses of [15N]glycine: evidence for a step function and a circadian rhythm in protein turnover.

1. The present study sought to determine the possible existence of a pool of proteins which turn over with life-time kinetics. The pattern of enrichment of ammonia and urea in hourly samples of urine was determined in normal adults to whom oral doses of [15N]glycine were given hourly for 36 h. The subjects received hourly meals throughout, and in six the study commenced at 06.00 hours, in five at 12.00 hours and in two at 18.00 h. 2. A plateau level of enrichment was achieved in urinary ammonia within 4-6 h. Regardless of the time at which the study started this plateau was held until about midnight, at which time there was an increase in enrichment, with a second higher plateau 5-6 h later. The second plateau was held to the end of the study. For urinary urea the rate of rise in enrichment was slower and smoother, because of the slow turnover of the urea pool. 3. Protein synthesis, derived from the first ammonia plateau, 179 mg h-1 kg-1, was significantly higher than that derived from the second plateau, 118 mg h-1 kg-1. Using the plateau in urea towards the end of the 36 h, the estimate of protein synthesis was 153 mg h-1 kg-1. 4. The results are considered to provide evidence of a pool of proteins for which degradation takes place in harmony with a circadian rhythm.

Pressure sore risk assessment in children.

A multi-centred study was undertaken involving 300 children ranging from neonates to children aged 16 years. The purpose of the study was to investigate the possibility of designing a pressure sore risk assessment scoring system suitable for the paediatric area of care. It was found that the following conclusions can be drawn: (i) Children are at risk of developing pressure sores; (ii) A version of the adult Waterlow card was not appropriate, especially at the younger end of the scale; (iii) There are identifiable situations and treatments which do pose a risk of pressure sore development. Admission documentation and a care plan within a hospital policy is recommended as the best method of drawing nurses' attention to the risk factors involved and the measures which need to be taken to alleviate the risk of tissue damage.

Effects of early disease on later growth, and early growth on later disease, in Khartoum infants.

Longitudinal data of monthly length and weight measurements, and fortnightly infectious disease records of 167 infants in Khartoum townships, have been examined to determine: (1) whether disease experience in the first 6 months of life is related to growth in the second 6 months and (2) whether growth in the first period is related to disease experience in the second. Using regression techniques to allow for disease measure correlations in the two periods and other environmental factors that are associated with growth and disease, it is concluded that both length and especially weight growth are affected adversely by previous illness. On the other hand there is almost no evidence that early growth is associated with later disease susceptibility.

Protein-energy malnutrition: the nature and extent of the problem.

The paper begins by describing how the names 'protein malnutrition' and 'protein-energy malnutrition' (PEM) developed from the local name 'Kwashiorkor'. The central feature of severe PEM is oedema; the classical theory suggests that the cause is a deficiency of protein, but other factors are also involved. In the community mild-moderate PEM is defined by deficits in growth. A distinction has to be made between low weight for height (wasting) and low height for age (stunting), Stunting in particular affects some 50% of children worldwide. Its causes and consequences are briefly discussed. In adults, severe PEM has essentially the same features as in children and includes the condition'famine oedema' or 'hunger oedema'; there are again controversies about its cause. In the community, chronic malnutrition is assessed by the body mass index (BMI) (Wt/Ht(2)). Grades of deficiency have been defined and examples are given of functional consequences of a low BMI. Secondary malnutrition differs from primary PEM because of the role played by cytokines and other concomitants of illness or injury. The importance is emphasized of chronicity or duration in determining the clinical picture.

Operating table. The root cause of many pressure sores?

The aim of this article is to suggest and justify the hypothesis that theatre tables and trolleys are probably the root cause of a large proportion of pressure sores in surgical areas. Pressure sores are also known as decubitus ulcers or bed sores, and are caused by the death of tissue when the blood supply to the capillary bed and/or deep tissue is occluded. This occlusion stops the tissue from being supplied with nutrients and also prevents waste products from being removed. Ways will be suggested of how the risk of developing these painful, costly -40,000 pounds plus for a serious pressure sore--and very largely preventable sores can be reduced. In order to do this, the article will attempt to cover aspects of the whole problem and not just concentrate on the theatre area.