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Proc. roy. Soc. Med. Volume 69 July 1976

may be possible to detect the early stages of developing zinc deficiency (Burns & Fell 1976). Biochemical effects: The activity of various zinc metalloenzymes in plasma, such as alkaline phosphatase, does show a reduction in acute zinc deficiency. However, little change is found in more marginal states. Defective protein synthesis can be demonstrated in the zinc-deficient animal, and in acute loss following surgery a previously resistant hypoproteinwmia responded to intravenous zinc therapy (Fodor et al. 1972). In vitamin-A-resistant night-blindness, observed in alcoholic chronic cirrhosis, there has been a suggestion that there is a reduced liver synthesis of retinol-binding protein and a reduction in retinine reductase activity, both zinc-dependent processes, and affected by the zinc deficiency induced by the urine losses in this disease (Halsted et al. 1974). Zinc Therapy As described above, various common clinical circumstances could combine to induce a degree of zinc deficiency. Replacement zinc therapy can be given orally or intravenously as zinc sulphate, and some guidance as to the amount of zinc required can be obtained from measurement of the known total losses. Furthermore, estimation of the appropriate zinc fractions in plasma may in future be of value. Although few serious long-term toxic effects have been described during the use of zinc therapy, there is room for the development of additional zinc pharmaceuticals in order to reduce the incidence of gastrointestinal upset reported during oral zinc sulphate therapy, and certainly further study is needed of suitable preparations for intravenous use.

REFERENCES Burns R R & Fell G S (1976) Communication to the Scottish Society for Experimental Medicine, Aberdeen (unpublished) Clayton B E (1973) Symposium on Advances in Laboratory Medicine. Royal College of Physicians of Edinburgh; Publication No. 44, pp 7-19 Cuthbertson D P, Fell G S, Smith C M & Tilstone W J (1972) British Journal ofSurgery 59, 925-931 Davies J W L & Fell G S (1974) Clinica chimica acta 51, 83-92 Fell G S (1975) Scottish Medical Journal 20, 101-102 Fodor L, Eschner J, Dick W & Ahnefeld F W (1972) Anasthesist 21, 456-459 Freeman J B, Stegink L D, Meyer P D, Fry L K & Denbesten L (1975) Journal of Surgical Research 18, 463-469 Halsted J A, Smith J C jr & Irwin M I (1974) Journal oJ Nutrition 104, 345-378 Hambidge K M, Hambidge C, Jacobs M & Baum J D (1972) Pardiatric Research 6, 868-874 Henkin R I (1971) In: Newer Trace Elements in Nutrition. Ed. W Mertz & W E Cornatzer. Dekker, New York; pp 255-312 Lancet

(1973) i, 299-300 (1975) ii, 351-352 Underwood E J ed (1971) Trace Elements in Human and Animal Nutrition. 3rd edn. Academic Press, New York; pp 208-252

16 Miss S K MacFarlane (Clinical Pathology Unit, Whittington Hospital, London N19) Measurement of Trace Elements in Urine For the investigation of trace element excretion the conventional 24-hour collection of urine has many drawbacks and limitations. Many of these elements are ubiquitous in the environment and there is a real risk of contamination at some stage of the collection. Pooled 24-hour urines, moreover, are cumbersome, and many prove to be incomplete. We therefore prefer an alternative approach based on 24-hour series of aliquots. The subject is asked to collect a sample of each urine passed during a 24-hour period. The sample can be as little as 10 ml and is passed directly into a small plastic universal container. This virtually eliminates any risk of contamination; and, since several small bottles can easily be carried around during a normal working day, the inconvenience of pooling large specimens is removed. Two measurements are then performed on each aliquot: the osmolality and the trace element concentration. The objection to using random urines in looking at urinary constituents has always been that no account is taken of the degree of dilution of the specimen. Consequently the normal range becomes so wide that it loses all diagnostic significance. Measuring the osmolality of each specimen largely overcomes this difficulty. The measurement is quick, simple and accurate; and by relating the trace element concentration to osmolality, the normal range is narrowed to within reasonable limits. The procedure is illustrated in Fig I A, B, C. First, the trace element concentration of each urine of a single 24-hour series of samples is plotted against the osmolality (Fig IA). Each point represents one aliquot of urine plotted in order of increasing osmolality, not chronologically. In Fig 1B'three separate 24hour series have been plotted in this way, joining the points to differentiate between individual series. After plotting the 24-hour series of about 50 control subjects it is possible to define a normal range which will include at least 95% of normal points. This is shown in Fig Ic. No attempt has been made to interpret the shape of the normal 'area', but the irregular wedge-shape is typical of most trace elements. Fig 2A, B demonstrates how abnormal excretion patterns are detected. The 24-hour series from a patient with a suspected abnormality is plotted in the way outlined and superimposed on the normal range. Abnormalities can show up in two ways. Fig 2A shows a 24-hour series with most of the points falling above the normal range area. This

Section of Measurement in Medicine

17

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Although the 24-hour series of urines was originally introduced to examine urinary calcium in potential stone-formers (Chambers & Dormandy 1967) it is most suited to the investigation of trace, elements, since their contribution to total urine osmolality can be disregarded.

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Fig 2A, an. abnormal 24-hour series with most points lying above the normal range area. e, an abnormal series where the curve is shifted to the left

means that at most times throughout the 24-hour period the patient is passing excessive amounts of the trace element, irrespective of osmolality. This type of abnormality would probably show up equally well on a 24-hour pooled collection. In Fig 2s the curve is shifted to the left: the trace element excretion is abnormal but only in relation to the total osmolality and only for part of a 24-hour period. This type of abnormal pattern would be missed in a 24-hour pooled collection since specimens with a high trace element concentration might be diluted by those in which the trace element concentration was low or normal. In other words the total excretion could be within 'normal' limits.

Meetings October 1975-February 1976 An educational course of ten lectures was held on the subject of Measurement Techniques Appropriate to Major Branches of Medicine and the following papers were read:

20 October 1975 Introduction: Recording and Measurement of Blood Pressure by Direct and Indirect Methods Dr P Cliffe (Westminster Hospital, London S W1P 2AP) 27 October 1975 Blood Flow in Organs and Tissues: Peripheral Vascular Disease Mr John Dormandy (St George's Hospital Medical School, London S WJ7 OQT)

REFERENCE Chambers R McK & Dormandy T L (1967) Lancet ii, 1378

The following papers were also read: Biological Significance of Trace Elements Dr T L Dormandy (Clinical Pathology Unit, Whittington Hospital, London N19) Cadmium and Mercury Mr A A Cernik (Occuipational Medicine & Hygiene Laboratories, Health and Safety Execuitive, Cricklewood, London NW2 6LN)

10 November 1975 Blood Flow in Arteries and Veins: Theory and Methods. Cardiac Output. Oximetry Dr P Cliffe (Westminister Hospital, London SWIP 2AP)

17 November 1975 Respiratory Physiology: Measurement Dr J P Blackburn (Westminster Hospital, London S W1P 2AP) Clinical Applications Professor C M Conway (Westminster Hospital, London S WIP 2AP)

24 November 1975 Blood Gas Analysis: pH, PCO2, P02 Dr J P Blackburn (Westminster Hospital, London S WJP 2AP) Acid Base Balance: in vivo and in vitro Methods Professor C M Conway (Westminster Hospital, London SWIP 2AP)

Measurement of trace elements in urine.

476 Proc. roy. Soc. Med. Volume 69 July 1976 may be possible to detect the early stages of developing zinc deficiency (Burns & Fell 1976). Biochemic...
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