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eaten by the children. Whole-meal and white flour

promoted equally good growth in animals eight weeksold when the experiment began ; only when they weregiven the diet immediately on weaning did whole-mealtlour show any superiority over white flour.The report includes a wealth of experimental data

which will be valuable to nutrition workers. For instance,balance studies showed that many children excreted inthe faeces more riboflavine than they were receiving intheir food.’ Clearly a diet based on wheat encouragesbacterial synthesis of this vitamin in the intestine. Adetailed dental survey by Dr. Helen Mellanby, recordedin an appendix, showed that during the year the increaseof caries among the children was not great.These observations, besides confirming the high

nutritive value of wheat, show that children can growwell on diets containing very small amounts of animalfoods. The M.R.C. workers are rightly cautious in theirconclusions. Their findings do not necessarily lend

weight to the argument that white flour can safely replaceflour of 85% extraction or whole-meal flour ; for theobservations were made in special circumstances. Allthe children were receiving larger quantities of freshvegetables daily than many children receive in our

industrial cities. The basic diet differed greatly from thebread-and-margarine diets on which many poor childrengrew up after the 1914-18 war.

1. Bucher, G. R. Gastroenterology, 1947, 8, 627.2. Spiro, H. M., Reifenstein, R. W., Gray, S. J. J. Lab. clin. Med.

1950, 35, 899.3. Eastcott, H. H. G., Fawcett, J. K., Rob, C. G. Lancet, 1953,

ii, 1068.4. Mirsky, I. A., Block, S., Osher, S., Broh-Kahn, R. H. J. clin.

Invest. 1948, 27, 818.5. Hirschowitz, B. I. Lancet, 1953, ii, 66.6. Sircus, W. Quart. J. Med. 1954, 23, 291.

DIAGNOSTIC USES OF UROPEPSINOGEN

WHEN a patient has characteristic symptoms ofduodenal ulcer but radiography after a barium mealshows no sign of an ulcer, it may be difficult to decidehow else to establish the diagnosis. Some still favour thefractional test-meal, but this test has many vagaries ; a

twenty-four-hour gastric pH curve is more instructivebut less practicable ; and occult blood in the faeces isa feature of too many conditions to be of direct help.Complicated duodenal ulcer may cause still greaterdifficulty in diagnosis. Pyloric obstruction and gastro-intestinal bleeding are sometimes the first manifestationsof an ulcer ; and gastric carcinoma or oesophagealvarices have to be excluded.There is, then, a need for a reliable test for active

duodenal ulcer. Possibly estimation of uropepsinogenmay prove such a test. Urine when made strongly acidshows proteolytic activity, due to uropepsin.1 Urinenormally contains the pro-enzyme uropepsinogen, whichis almost certainly identical with the pepsinogen in thegastric glands ; it reaches the kidneys via the blood andis excreted at a fairly constant rate. This rate is affected

by the protein content of -the diet,! by the level ofadrenocortical activity,2 by operations on the stomach,3and-most important of all-by gastric overactivity ofthe type found in patients with duodenal ulcer.4 It is

fairly generally agreed that patients with duodenal ulcerexcrete about twice the amount of uropepsinogenexcreted by healthy people or by patients with gastricule-er or carcinoma of the stomach. Hirschowitz 5

concluded that the longer the history of duodenal ulcerand the nearer a lesser-curve ulcer is to the pylorus, thegreater is the uropepsinogen-excretion rate. Sircus 6has described a new method of assay dispensing withhæmoglobin, previously the most commonly used sub-strate for uropepsin. He found that pooled dried plasmagave reproducible results, and in a series of studies onpatients showed that the activity of duodenal ulceration? constantly related to the level of uropepsinogen

excretion. He also observed that, whereas after successfulpartial gastrectomy the level usually fell to zero, two

patients with stomal ulcer had a low normal level.Sircus’s figures provide a convincing case for the use ofthis test in hæmatemesis. Ten patients in whom thesource of the bleeding was a duodenal ulcer showed auropepsinogen excretion over twice as high as that ineight others in whom the cause was gastric ulcer, acuteulcer, or oesophageal varices.

If estimation of uropepsinogen, perhaps further simpli-fied, can be brought into routine use we may expect itto prove as useful in diagnosis as it has already provedin clinical research.

1. Thannhauser, S. J., Stanley, M. M. Trans. Ass. Amer. Phycns,1949, 62, 245.

2. Malmros, H., Swahn, B., Truedsson, E. Acta med. scand.1954, 149, 91.

3. Wijnhanssen, O. J. Berlin. Klin. Wschr. 1921, 58, 1268.4. Brunner, W. Klin. Wschr. 1935, 14, 1853.5. Collett, R. W., Kennedy, R. L. J. Proc. Mayo Clin. 1948,

23, 158.6. Poulson, H. M. Acta. med. scand. 1950, 138, 413.7. Klatskin, G., Gordon, M. Amer. J. Med. 1952, 12, 3.8. Thannhausser, S. J. The Lipoidoses. New York, 1950.9. Lever, W. F., Smith, P. A. J., Hurley, N. A. J. invests Derm.

1954, 22, 33.

ESSENTIAL HYPERLIPÆMIA

HYPERLIPÆMIA may arise from three causes. It maybe : (1) alimentary, reaching a maximum four to sixhours after a meal rich in fat ; (2) secondary to someother disease, such as diabetes mellitus or nephrosis ; or

most rarely (3) idiopathic. This third form often occursin families, and there is some evidence that the abnor-inality is due to subnormal ability to remove neutral fatfrom the blood.1 Only 41 such cases had been reportedup till this year, when Malmros et a1.2 have describedtheir observations on 10 more patients, of whom 5 weremembers of one family and 2 of another. They investi-gated the relatives of the remaining 3 patients, butnone showed the abnormality, though in some the totalserum lipids and cholesterol were at or above the upperlimit of normal. Of their cases, 5 had cutaneous xantho-mata on the elbows and extensor surfaces of the arms,the buttocks, and the knees. In all but 1 of these 5the xanthomata persisted despite dietary treatment andrecurred after surgical removal ; but in the 1 patient whofollowed the dietary regime very closely the skin lesionsdisappeared completely. None had lesions of the tendons,which are common sites in patients with hypercholester-aemic xanthomatosis. 2 patients had infiltration of theskin creases of the palms of the hands, with earlycontracture. None had an enlarged liver, and only 1 hadsplenomegaly (enlargement of one or both of theseorgans has been found in about half the recorded

cases).Acute pancreatitis is associated with hyperlipaemia.3-’

Thannhauser 8 regards the pancreatitis as primary ; butthe facts that in several recorded cases cutaneousxanthomata have preceded attacks of pancreatitis, thata patient had hyperlipsemia eight years after the lastattack of pancreatitis, and that some patients withhyperlipæmia and pancreatitis have had relatives withsymptomless hyperlipæmia suggest that the pancreatitisis secondary to the hyperlipæmia.7Malmros et al. found that in their cases the plasma

varied from opalescent to creamy. The total neutral-fatcontent was grossly increased, as were free and totalcholesterol and plasma-phospholipids. Paper-electro-phoresis of the serum-lipoproteins showed a gross increasein &bgr;-globulin with an even higher chylomicron peakimmediately following, which reflected the increase ofcholesterol and phospholipids on the one hand and ofneutral fats on the other. Lever et a1.9 compared 7 casesof essential hyperlipaemia with 10 cases of primaryhypercholestersemic xanthomatosis. (Their cases of

idiopathic hyperlipaemia included 1 patient with diabetes,

1008

and it is doubtful whether this case should have beenincluded as an example of the primary disease.) Theirclinical and laboratory observations on essential hyper-lipaemia agree closely with those of Malmros and hiscolleagues. They found that the high p-globulin peakcould be reduced to normal by extracting the serumwith fat solvents before electrophoretic analysis. Contraryto the view of Thannhauser that there is no associationwith coronary-artery disease, both Malmros and Leverfound a high incidence of this in their patients withessential hyperlipaemia. The association is not surprisingin view of the high blood-cholesterol levels in essentialhyperlipsemia, and also the real or apparent increase ofthe {3-globulin fraction of the serum-proteins whichMalmros and Swahn 10 have found in patients with

myxcedema and cardiac infarction, and in rabbits withatheromatosis due to feeding with cholesterol.

Treatment by a diet low in, or free of, fat reducesthe turbidity of the plasma,2 9 and if followed closelyenough causes regression of the cutaneous lesions.2Injections of heparin have been found to reduce theturbidity of the plasma of healthy people after a fattymeal, and Swank 13 showed that heparin increasedthe tendency of chylomicra to cluster together-a changewhich he detected during the natural clearing of the blood-plasma in alimentary hyperlipsemia. Lever and his

colleagues found that intravenous heparin cleared theplasma of their patients with essential hyperlipsemia,and also caused distinct changes in the electrophoreticmobilities of the lipoprotein fractions. Malmros et al.,on the other hand, found that after injection of heparinthe serum of their patients was still milky, and theywere sceptical of the value of this drug. It seems doubtfulwhether treatment with heparin is justified, in view ofits effect on blood-clotting and the transiency of itseffects on the hyperlipaemia. Strict adherence to a low-fat diet, or a diet containing predominantly vegetablefats, will correct not only the turbidity of the serum(which is no inconvenience to the patient) but possiblyalso the cutaneous lesions, which are both painful anddisabling. Such a diet may also lessen the risk of

coronary-artery disease.

10. Malmros, H., Swahn, B. Nord. Med. 1952, 48, 1028 ; Actamed. scand. 1953, 145, 361.

11. Hahn, P. F. Science, 1943, 98, 19.12. Block, W. J., Barker, N. W., Mann, F. D. Circulation, 1951,

4, 674.13. Swank, R. L. Amer. J. Physiol. 1951, 164, 798.14. Sherlock, S., Summerskill, W. H. J., White, L. P., Phear, E. A

Lancet, Sept. 4, 1954, p. 453.15. Hughes, W., Dodgson, M. C. H., MacLennan, D. Ibid, Oct. 18,

1954, p. 770.16. Waggoner, R. W., Bagchi, B. K. Amer. J. Psychiat. 1954,

110, 904.

MENTAL CHANGES AND ORGANIC DISEASE

OF the dementias caused by organic disease of thebrain general paralysis of the insane is perhaps the bestknown ; but mental changes may also arise frommetabolic disturbance 14 and cerebral arterial disease.15In addition, focal brain disease may give rise to a picturepredominantly of mental disorder. Frontal tumour orabscess, for instance, may produce a conduct abnormalityvery similar to that of G.P.I., and recently the psychiatricsyndromes associated with lesions of the temporal lobehave been much discussed. Such syndromes are pre-sumably due to direct interference with local neuronalmechanisms ; but local space-filling lesions may also

produce a more general disorder as a result of the hydro-cephalus or rise in intracranial pressure that they cause,and the resulting confusional state may mask focal

symptoms and signs. The patient, especially if elderly,may be admitted to a mental hospital where, if the

diagnosis is still missed, he may be unsuitably treated-for example, by electroconvulsive therapy.Waggoner and Bagchi 16 suggest that electro-encephalo-

graphy (E.E.G.) should be done routinely in psychiatric

cases ; they cite six cases in which a psychiatric diagnosiswas abandoned after localised abnormalities had beenfound in B.E.G.s. There is no doubt that such an applica-tion of E.E.G. is occasionally valuable in both neurologicaland psychiatric practice ; but its routine use as recom-mended by Waggoner and Bagchi is likely to give riseto other diagnostic mistakes.

1. Evans, A. S. Amer. J. Hyg. 1954, 60, 204.2. Morimoto, M., Morgan, H. R. Proc. Soc. exp. Biol., N.Y. 1954,

86, 795.3. Buck, G., Quesnel, J. J., Ramambazafy, H. D. Ann. Inst.

Pasteur, 1954, 87, 450.4. Takaoka, Y., Yamaguchi, T., Yamada, N., Kosaka, K. Klin.

Wschr. 1954, 32, 369.5. Sposito, M., Cheli, R. Rif. med. 1951, 65, 1250.6. McCance, R. A., Dean, R. F. A., Barrett, A. M. Spec. Rep. Ser.

Med. Res. Cown., Lond. no. 275. H.M. Stationery Office, 1951;p. 135.

7. Greengard, H. In Pincus, G., Thimann, K. V. The Hormones.New York, 1948 ; vol. 1.

NEWCASTLE DISEASE AND MUMPS VIRUS

Newcastle disease affects mainly chickens andturkeys ; but infection of man has been reported,mainly among those handling infected birds. Generallyin man the effects are confined to mild conjunctivitisand other minor symptoms ; but more severe respiratoryinfections have been described, and possibly some

unexplained illnesses may be attributable to theNewcastle-disease virus (N.D.v.).

Antibodies neutralising the virus appear in the blood-stream of some people exposed to the disease, but testsof the N.D.v.-neutralising ability of the serum are nota reliable criterion of infection for two reasons. Firstly,neutralising antibodies cannot be detected in all infectedpatients, and secondly components reacting serologicallywith N.D.V. can be detected in the sera of some patientsconvalescing from mumps or infectious mononucleosis.There is also overlapping of the serological specificitiesof virus haemagglutination inhibitions between Newcastledisease, mumps, and influenza. From virus neutralisationtests it seems that there are several strains of mumpsvirus,’ and that at least one of these is serologicallyrelated to some strains of N.D.v. The complexity of themumps virus itself is illustrated by differences betweenits haemagglutinating and its hsemolytic effects,2 whichare apparently due to distinct and separate agents.Many virus specificities are no less complex. Newcastle

disease although common only in chickens and turkeys,can be transmitted to hamsters, mice, and other animalsas well as man. Pigs and sheep are resistant to intra-venous inoculation of N.D.v., but can be infected intra-

cerebrally.3 After several passages in young pigs byintracerebral inoculation N.D.v. infects pigs inoculatedintranasally, but during this adaptation to a new hostthe virus progressively loses first its virulence and thenits immunising effect in chickens. Pigs resistant to

infectious paralysis produced by the Teschen virus areimmune also to intracerebral infection by N.D.v.

ENLARGEMENT OF THE PAROTID GLANDS

ENLARGEMENT of the parotid glands has been notedin diabetics,4 in cirrhotics,5 and during recovery fromundernutrition.6 Histological studies 5 6 may show hyper-plasia and an increase of fat in the glands, but themechanism of the enlargement is obscure. Attempts toestablish whether the parotids have a role in carbo-hydrate metabolism have led to contradictory results.’Different authors have ascribed a hypoglycaemic and ahyperglycaemic action to the glands, and some of themost careful work has failed to reveal any action at all.Takaoka et awl. have now found insulin activity in theparotid glands from two diabetic patients and from sixalloxan-diabetic dogs, but not in glands from a patientwithout diabetes or from normal animals, nor in other