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ochronosis-a word coined by Virchow,14 who firsidescribed the pathological findings in alkaptonuria andwished to distinguish the disorder from melanosis.

14. Virchow, R. Virchows Arch. 1866, 37, 212.15. Lancet. May 7, 1955, p. 958.16. Greiner, T., Henry, J. P. J. Amer. med. Ass. 1955, 157, 1373.17. Bull, G. M. Clin. Sci. 1948, 7, 77.18. Farber, S. J., Becker, W. H., Eichna, L. W. J. clin. Invest

1953, 32, 1145.19. King, S. E., Baldwin, D. S. Proc. Soc. exp. Biol., N.Y. 1954

86, 634.20. Gough, J. In Recent Advances in Pathology. Edited by G

Hadfleld. London, 1953 ; p. 199.21. Doll, R. Brit. J. industr. Med. 1955, 12, 81.

THE CAUSE OF POSTURAL PROTEINURIA

A FEW weeks ago we said that the mechanism of

postural proteinuria was still unknown.15 An importantcontribution has since been made by Greiner and

Henry.I6 These workers criticise the view 17 that the

proteinuria is directly due to increased pressure in theinferior vena cava and renal veins, and refer to an

experimental study 18 in which increase of caval pressureto 150-220 mm. saline, maintained for thirty minutes,caused no proteinuria.

Carefully controlled observations in six young menwith postural proteinuria indicated that the most impor-tant setiological factor is pooling of blood in the extremi-ties. Advantage was taken of the fact that posturalproteinuria is particularly liable to occur in hot con-ditions,17 and all the observations were made at a

temperature of 122°F. Lordosis in the supine positionproduced proteinuria once only, whereas venous-occlusioncuffs applied at a pressure of 80 mm. Hg to all fourlimbs resulted in proteinuria in all the subjects. Pro-

teinuria, which regularly occurred after tilting the

subjects to a 70° head-up position, was prevented bycompression of the legs, which effectively inhibited

peripheral pooling of blood.Greiner and Henry point out that their observations

explain the facts that postural proteinuria is commonerin hot conditions producing peripheral vasodilatation,and in motionless standing 17 which is particularly liableto cause pooling of blood in the legs. They suggest thatdeviation of blood from the heart and lungs causesarterial vasoconstriction which is proportionately greaterin the renal arterial system. The erect lordotic posturegreatly reduces the renal plasma flow,19 but this fall isno greater in cases of postural proteinuria than in

non-proteinuric controls.

LUNG CANCER IN ASBESTOSIS

THE causes of cancer of the lung are probably mainlyexogenous,20 but each of the definitely known carcinogenicsubstances-e.g., ores in Schneeberg and Joachimstalmines, bichromates--accounts for only a minute pro-portion of all cases. Doll 21 now confirms suggestiveevidence that lung cancer is an occupational hazardof asbestos workers. Examination of the cause of deathin 105 persons who had been employed in one asbestosworks showed that 18 had had lung cancer, associatedin 15 cases with asbestosis. The mortality of 113 menwho had worked for at least twenty years in placesexposed to asbestos dust was compared with the

mortality experience of the whole male population.There were 39 deaths in the first group, whereas 15.4were expected : the excess was due to deaths from lungcancer (11, compared with 0.8 expected) and from otherrespiratory and cardiovascular diseases (22, comparedwith 7.6 expected). The average risk among menemployed for twenty or more years has been of the orderof ten times that experienced by the general population.This risk has become progressively less since the pre-cautions introduced as a result of the Asbestos Industry

Regulations, 1931, to prevent dust dissemination inthe works became effective.

Gloyne 22 found in -his series of 1205 specimens oflungs with dust diseases, including 121 of asbestosis,that the rates for primary neoplasm of the lung in maleand female asbestos workers were 20% and 10%respectively. Barnett 23 found 31 deaths with carcinomaof lung in 235 deaths associated with asbestosis duringthe years 1924-46, with a distribution of 17-2% maleand 8.4% female deaths. Adjustments for length of

exposure to the dust and age at death would scarcelyaccount for the discrepancy in the figures between thetwo sexes. The same discrepancy exists in the figuresfor all cases of carcinoma of the lung : Kennaway andKennaway 24 showed that the rates of female to maledeaths in England and Wales had changed from I : 1-9in 1921 to 1 : 4-0 in 1945 ; between 1935 and 1945 theincrease was 256% for males and 176% for females.If the causes of cancer in the lung are the same for bothsexes (as in asbestosis and possibly in smoking), canthe sex discrepancy be related to the baffling fact that,while the total " amount " of tumour in both sexes is

approximately equal, 40% of the cancer deaths in femalesare from carcinoma of organs peculiar to the female,25

leaving correspondingly smaller numbers for othersites ? If so, what internal factor determines this organselectivity

Unlike asbestosis, the main causes of dust diseases inthe lungs are not associated with an increase in carcinomaof the lungs ; and Kennaway and Kennaway 2 showedthat bronchial carcinoma is less common in coal-workersthan in the general population. James 27 has confirmedthis very neatly by comparing a series of South Walescoalminers with a series of non-miners in the same area,obtaining figures of 3.3% for the former and 5.4% forthe latter ; but he points out that the relatively lowincidence of tumour in the miners may be partly due todust disease causing death before the average cancerage. The dust diseases generally act on the connectivetissues, and there is no satisfactory explanation of whythe asbestos fibres should affect the epithelium as well.

22. Gloyne, S. R. Lancet, 1951, i, 810.23. Barnett, G. P. Annual Report of the Chief Inspector of Factories

for the year 1947. H.M. Stationery Office, 1949.24. Kennaway, E. L.. Kennaway, N.M. Brit. J. Cancer, 1947, 1, 260.25. Kennaway, E. L. Brit. med. J. May 7. 1955, p. 1107.26. Kennaway, E. L., Kennaway, N.M. Brit. J. Cancer, 1953, 7, 10.27. James, W. R. L. Brit. J. industr. Med. 1955, 12, 87.28. Meyers, R. Epilepsia, 1954, 3, 1.29. Gibbs, E. L., Gillen, H. W., Gibbs, F. A. Amer. J. Dis. Child.

1954, 88, 596.30. Gibbs, E. L., Fleming, M. M., Gibbs, F. A. Pediatrics, 1954, 13, 66.

EPILEPSY AND THE ELECTRO-ENCEPHALOGRAM

IMPROVED techniques of electro-encephalography(E.E.G.) have confirmed some earlier correlations ofelectrical with clinical activity, such as that of bilateral3-per-second wave-and-spike patterns with petit mal;have led to the modification of some, such as that of

square-topped waves and a sharp down peak with

psychomotor epilepsy ; and have cast renewed doubton others, such as the identification of the cortical spikefocus with the site of origin of an epileptic discharge.28

Gibbs and his colleagues 29 30 have described valuableinformation about the natural history of E.E.G.

abnormalities which has important clinical implications.By following changes in E.E.G. patterns as infants andchildren develop, they have obtained a " longitudinalsection " of electrical brain activity to supplement thebrief " cross-sectional " view of isolated E.E.G. recordings.They point out that the immature brain tends to reactto various possibly epileptogenic traumata with a

generalised electrical abnormality. Moreover the patternof reaction differs at different stages of maturation.In infancy " hypsarhythmia " (continuous slow-wavehigh-voltage discharge with diffuse spiking) is common ;

1164

as the first decade of life is traversed, at first " petit-mavariant " (2-per-second sharp-and-slow waves) and thei" classical petit mal " (3-per-second wave-and-spik<activity) are more usual. In adolescence and adult liftthe electrical response to cerebral insult becomes mor(localised. This is so with epileptogenic factors occurringab initio at this age, and may also apply to activityshown earlier as a generalised response in (,IiildhoodFocal activity, though less common, does also occur inchildhood, and, unlike the generalised response, it mayclear spontaneously or change in form and site as ageadvances. Thus occipital foci, present rather more

often in the 1-5 age-group, had tended by the age of 9either to disappear (40%) or to change their location(37%) to a temporal or possibly subcortical site ; while

midtemporal foci, by the age of 15, had either cleared(54%) or migrated to an anterior temporal or subcorticalsite (38%).

Gibbs and his school have done a great deal to advancethe clinical value of electro-encephalography, and thesestudies put us further in their debt. The evidence thatsome focal abnormalities disappear spontaneously withage will be welcome to all those dealing with epilepsy,in childhood. It confirms clinical observation and under-lines the need for caution in excising " epileptic foci,"especially in the young. Moreover, the change in focusonce more raises the question of whether the primarysite of epileptic discharge is cortical. Gibbs et al. speakof " migrating foci," which is a vivid description ; butthe change may be due to altered activity in one partof a complex neuronal circuit allowing activity alreadypresent in another part to emerge more clearly. Westill know too little of what the E.E.G. pattern representsin terms of cellular neurophysiology.

This work has further value in posing many clinicalquestions. We are not told what proportion of thosewith focal and general E.E.G. abnormalities had focal orgeneral fits ; nor is it clear, apart from the statementthat " many develop multiple foci," what happens asage advances to the varying forms of generalised abnor-mality found in childhood. Finally we need to find outthe proportion of children who show these abnormalitiesbut have no clinical attacks at all.

1. Walsh, B. J., Bland, E. F., Taquini, A. C., White, P. D. Amer.Heart J. 1941, 21, 689.

2. Breyfogle, H. S. J. Amer. med. Ass. 1940, 114, 1434.3. Wolferth, C. C. J. Mt Sinai Hosp. 1942, 8, 1121.

GALL-BLADDER AND HEART-BLOCK

CONFLICTING views are held on the relations betweenthe gall-bladder and the heart. These fall under three

headings-namely, the differential diagnosis between

angina, pectoris and the pain of gall-bladder disease,the coincidence of gall-bladder disease and coronary-artery disease in the same patient, and the possibilitythat gall-bladder disease may aggravate existing heart-disease.

White and his co-workers reported clear evidence ofdisease of the gall-bladder in 6-8% of 1000 patients, whopresented clinically with coronary-artery disease. Theyfound at necropsy that disease of the gall-bladder wasalmost twice as common in patients with severe coronary-artery disease as in those with normal coronary arteries.This association, they suggested, was related to an

ageing process. Breyfogle,2 on the other hand, concludedfrom a comparable necropsy study that the associationbetween gall-bladder disease and coronary-artery diseasewas independent of age and sex. Wolferth 3 wonderedwhether the two diseases shared a similar metabolic

pathogenesis. But there is a striking difference in thesex-distribution of coronary-artery disease, with malepreponderance, which has not been found in disease ofthe gall-bladder.

,1 Whether gall-bladder disease aggravates angina pectorisn is still uncertain, but there is now clear evidence that it:e influences arrhythmias. McLemore and Levine’ reporr?e 7 cases of heart-block and gall-stones; recent hiliarr ’v’e symptoms had been present in all. They concludedg that the heart-block was due to coronary-artery diseasey or hypertension in 5 ; in 1 it was possibly congenital.1. and in the 7th it might have been due to diphtheria inn childhood. 5 had complete heart-block with frequenty Stokes-Adams attacks ; 1 had first-degree heart-blocke with sinus pauses and syncopal episodes ; and the 7tlie had an episode of transient complete heart-blocli accom.9 panied by an upset of consciousness. Preventive measuresahad failed adequately to relieve these attacks. All thesee patients underwent cholecystectomy. 4 were strudnglyIimproved, with no subsequent attacks of loss of con.

1 sciousness for six months or longer ; preoperatively these4 patients had experienced such attacks very frequently-

aup to four times a day. The remaining patients were alsoimproved, with definite diminution in the frequency oft the attacks. Anaesthesia was not thought to have1 contributed to their improvement. Asystole duringT operation called for special measures in 3 of the patients,- but all withstood operation well. McLemore and Levine, reasonably conclude that in patients with Stokes-Adams attacks, and especially where these have persisted despiter treatment, disease of the gall-bladder should be sought. The physiological basis of cholecystectomy in heart-; block is not completely clear. McLemore and Levine’tj clinical observation is supported by experiments on the- frog,5 and comparable but inconclusive observations have been made experimentally in man. Swallowing has beenl found to precipitate Stokes-Adams attacks ; Weiss and

Ferris 7 recorded three cases in which Stokes-Adamsattacks were brought on in this way, and suggested thatthey were due to a vagal reflex. In 1 of their patients atraction diverticulum of the cesophagus was present.Distension of the diverticulum by a rubber balloon led toauriculoventricular dissociation and syncope. Releaseof the distension was followed by a return to normalsinus rhythm and the disappearance of symptoms.Atropine abolished the symptoms and the heart-block.Mackenzie 8 found in a patient with rheumatic carditisthat either digitalis or swallowing delayed auriculo-ventricular conduction. But it is still difficult to definethe precise action of the vagus and the sympatheticnerves on the heart in the intact animal. 9

Another drug has been added to those that may beuseful in the medical treatment of heart-block-namely.sodium lactate. Bellet et al.10 have found sodium lactateof value in resuscitating the heart after cardiac arrest, intreating ventricular standstill in Stokes-Adams attach,and in otherwise increasing the ventricular rate in

complete heart-block. The drug was given by intravenousinjection or infusion.

These two promising new methods of treating heart-block will no doubt be widely tested. Both may provemore commonly effective than the artificial pacemaker."

We regret to record the death of Dr. C. W. BucKLEY.who was senior physician to the Devonshire Hospitalfor Rheumatic Diseases, Buxton, and of Dr. ROBERTFLEW, formerly physician to the Hospital for SickChildren, Great Ormond Street.

4. MeLemore, G. A. jun., Levine, S. A. Amer. J. med. Sci. 1955,229, 386.

5. Buchbinder, W. C. Proc. Soc. exp. Biol., N.Y. 1930, 27, 540.6. Hedge, G. B., Messer, A. L. Surg. Gynec. Obstet. 1918, 86, 617.7. Weiss, S., Ferris, E. B. jun. Arch. intern. Med. 1934, 54, 931.8. Mackenzie, J. Brit. med. J. 1906, ii, 1107.9. Gregg, D. E. Coronary Circulation in Health and Disease.

London, 1950.10. Bellet, S., Wasserman, F., Brody, J. I. Circulation, 1955

11, 685.11. Zoll, P. M., Linenthal, A. J., Norman, L. R. Ibid, 1951, 9, 482.