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agents as for transmitters of neural origin. Further,their assumption that the much smaller number of nervefibres going to the vascular smooth muscle in small

parenchymal vessels is merely a reflection of the reducednumber of muscle fibres requires confirmation by quan-titation of nerve/muscle fibre ratios. In other areas ofthe peripheral systemic vasculature differences in inner-vation and intermuscular connections correlate with the

predominant method of control.12 Such information is

required on the cerebral microcirculation if the conflict-ing views are to be properly appraised.Much remains to be discovered, but the previous

simple model for control of cerebral circulation is clearlyadequate no longer. Physical and neural factors operatealong with the traditional circulating and local humoralagents. Such a multiple-control system will be far moreadaptable than a single control loop. If neural mechan-isms are important, we must look again at the use ofvasoactive drugs in general and localised cerebrovascu-lar disease. Even though such drugs may increaseoverall cerebral blood-flow, they could well result in alocal cerebral steal,13 with reduced flow to an area withalready precarious nutrition.

SEVESO

THE incident at the Icmesa chemical plant near Milanhas highlighted the potential hazards associated with thesynthesis of 2,4,5-trichlorophenol, a compound used inthe preparation of various herbicides and bactericides.The industrial synthesis is relatively simple and involvesthe alkaline hydrolysis of tetrachlorobenzene at raisedtemperatures. If the temperature is allowed to exceed225°C the reaction can become exothermic and the reac-tor may release its contents explosively. At the same timean unwanted contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (T.C.D.D.), is formed. T.C.D.D. is solid and inthese circumstances would be distributed in a cloud of

droplets.T.C.D.D. is one of the most toxic compounds known: in

the guineapig the oral L.D.50 is 0-6 fLg/kg; other speciesof laboratory animal are less sensitive.14 Human beingshave been exposed in the United States, Germany, andCzechoslovakia, and the Italian experience resemblesclosely an incident in Derbyshire.15 A common feature incases of human poisoning is chloracne, a persistent anddisfiguring form of acne which has been associated withvarious chlorinated compounds. Chloracne appearsabout six weeks after exposure. Other reported symp-toms include hirsutism and personality changes, andthere can be signs of liver malfunction. The treatmentof T.C.D.D. poisoning is purely symptomatic and is com-plicated by the metabolic and chemical stability of themolecule. These factors, combined with a high lipid/-water partition coefficient, mean that T.C.D.D. is concen-trated in the liver and fatty tissues; hence the half-lifein the body is long.

If the release of T.C.D.D. at Seveso is confirmed, the

12. Folkow, B., Neil, E. in Circulation; p. 269. London, 1971.13. Symon, L. Int. anæsth. Clin. 1969, 7, 597.

14. Schwetz, B. A, Norris, J. M, Sparschu, G. L., Rowe, V. K., Gehring, P.J., Emerson, J. L., Gerbig, C. G. Environ. Hlth Perspectives, 1973, issue5, p. 87.

15. May, G Br. J md. Med. 1973, 30, 276.

authorities will have two main problems. Firstly, they willhave to analyse enough samples to define the amount ofT.C.D.D. released and the extent of the contaminatedarea. Since T.C.D.D. is very firmly bound to soil and isnot translocated in groundwaters, the area of contami-nation is not necessarily as large as that in which pheno-lic odours are detectable. Secondly, they will have todecide on the best measures for decontamination. Inareas only slightly contaminated it may be possible to re-strict access and to rely on slow microbial and photolyticbreakdown. In other areas it could be necessary to

remove and bury the topsoil and vegetation. Fire is un-likely to be helpful since T.C.D.D. is stable up to tempera-tures of 700 °C; only in an efficient incinerator will com-bustion destroy T.C.D.D. concentrates.The need for care in the disposal of T.C.D.D. residues

is evident from American experience. T.C.D.D. wastes

were disposed of as a mixture with waste oils and themix was subsequently used to control dust in horsearenas. 48 out of 85 hor.ses exercised in one arena died,along with other farm animals and local wildlife.16

SURGERY FOR ENDOMYOCARDIAL FIBROSIS

ENDOMYOCARDIAL fibrosis is mainly a disease of tropi-cal regions,17 but the occasional case is seen from tem-perate parts.18 With medical treatment the prognosis isalways grave’9-not surprisingly, since patients usuallypresent with advanced fibrosis of the ventricular inflowtracts extending to the atrioventricular nodes and pro-ducing mitral or tricuspid incompetence.17 With left-ven-tricular lesions, especially when the mitral valve is

affected, the prognosis is very poor; the longest survi-vors19 are patients who present with right-heart lesions,in whom the function of the obliterated right-ventricularcavity is taken over by a high venous pressure made pos-sible by a very tense ascitic abdomen. It is these whoshow the proptosis and the periorbital congestion typicalof the disease. 20

Surgical intervention offers hope of relief. 21 The dis-ease is one in which the heart only is affected, lesions inother organs being secondary. The fibrosis, howeverextensive on the mural endocardium, is of almost evendepth, with the outer portions of the myocardium freeof disease and, for the most part, a distinct line of cleav-age between the fibrous tissue and the normal myocar-dium. Finally, thrombosis, even on the fibrosed endocar-dium, seems distinctly uncommon.The earliest operations in this disease were usually

done with a view to relieving pericardial rather thanendocardial constriction, and almost all ended disas-

trously. But with improved methods of diagnosis andstrict localisation of the affected areas more definitive

surgery was possible. Thus Lepley et al. 22 operated on an

16. Carter, C. D., Kimbrough, R. D., Liddle, J. A., Cline, R. E., Zack, M. M.,Barthel, W. F., Koehler, R. E., Phillips, P. E. Science, 1975, 188, 738.

17. Connor, D. H., Somers, K., Hutt, M. S. R., Manion, W. C., D’Arbela,P. G. Am. Heart J. 1967, 74, 687; 1968, 75, 107.

18. Brockington, I. F., Olsen, E. G. J., Goodwin, J. F. Lancet, 1967, i, 583.19. D’Arbela, P. G., Motazindwa, T., Patel, A. K., Somers, K. Br. Heart J.

1972, 34, 403.20. Jaiyesmi, F., Falase, A. B. Trop. Cardiol. 1976, 2, 5.21. Bertrand, E., Renambot, J., Chauvet, J., Assamoi, M. O., Ekra, A. ibid.

p. 37.22. Lepley, D., Aris, A., Korns, M. E., Walker, J. A., D’Cunha, R. M. Ann.

thorac. Surg. 1974, 18, 626.

298

18-year-old girl (a native of Wisconsin, whose only tropi-cal contact was a pet monkey), very severely incapaci-tated with left-ventricular endomyocardial fibrosis andmitral-valve involvement. The mural fibrous tissue was

peeled off the underlying myocardium, a distinct clea-vage line being found despite odd tongues of more

deeply penetrating fibrous tissue. After clearance offibrosed tissue from the ventricle, the mitral valve wasreplaced by a Bjork-Shiley prosthesis. The myocardiumrapidly responded, a new normal-sized left-ventricularcavity was restored, and nine months later the patientwas completely symptomless and living a normal lifewithout evidence of cardiac disease. This case showedthe favourable prospects of surgery for the left-sidedlesions, while the cases reported by Sadeghi and Jaeger23and Pringent et al. 24 showed the possibilities of surgicalsuccess where both ventricles were involved. These sur-

gical interventions are discussed by Bertrand et al.,21who report a case at Abijan in which a patient operatedon for biventricular involvement survived for 21months. Death in their case was hastened by persistingtricuspid insufficiency, right-ventricular inefficiency, andconduction disturbances. On the favourable side was therelative ease of the surgical procedure, the rapid im-provement in the function of the myocardium once theconstriction was removed, and the fact that there was noincrease in left-ventricular damage over the period ofobservation. In all cases of endomyocardial fibrosis thepossibilities of operation should be considered. 25

WHOSE TURN NOW?

SPINA-BIFIDA children are growing up. Survivors fromthe earliest days of active treatment are in their teensand, to judge from a report by Dorner,26 they have mixedfeelings about the future. Their misgivings are no doubtshared by the doctors who have seen them through achildhood that has taxed clinical, social, financial, andemotional resources and which has spawned the spe-cialty of paediatric surgery. Who should now supervisetheir medical care in early adult life? Paediatricians willprobably withdraw-not least because the facilities of achildren’s unit are clearly inappropriate to a group whoneed every encouragement to be become adults. Theburden on specialist surgical departments (neurosur-gery, orthopaedics, urology) diminishes, but contact

must be maintained. Nephrology will face more work asthe years go by.The need remains for a co-ordinator. If hospital

based, an obvious choice is the specialist in rheuma-tology and rehabilitation; otherwise, strangely, the geria-trician, who knows the social services and often cares forthe young chronic sick. May not now be the time forthese patients to be discharged from hospital to the pri-mary-care team? Sadly, because of their dependence onhospital facilities, some children will not have met theirgeneral practitioner. Plans must soon be made, and itwould be prudent and courteous to consult the patients.

23. Sadeghi, H., Jaeger, M. Med. Hyg., Geneva, 1973, 31, 965.24. Pringent, C., Baculard, P. Charpentier, A. cited by Bertrand et al., ref. 5.25. Roberts, W. C., Ferrans, V. J. Hum. Path. 1975, 6, 287.26. Dorner, S. Archs Dis. Childh. 1976, 51, 439.

I.R.D.S. AND THE KIDNEY

NEONATOLOGISTS are familiar with the cardiovascularand cerebral complications of idiopathic respiratory dis-tress syndrome (I.R.D.S.),1 but they have rather neg-lected the kidneys. Information which in an adult is

regarded as indispensible for management of respiratoryfailure (accurate fluid balance and blood-pressurerecords) is not obtained easily in the small baby, andsigns of renal insufficiency may be overlooked. A Swissgroup, Guignard and co-workers,2 have investigatedrenal function in babies with I.D.R.S. of varying severityassessed by radiological criteria.3 With "informed paren-tal consent" studies were also done on control low-birth-

weight infants. Glomerular filtration, measured by inu-lin and para-aminohippurate clearances, was decreasedby one-third from control values in moderate I.R.D.S.

and by more than half in severe cases: the blood-ureawas twice that of normal infants. These results contra-dict another study4 in which renal function was normalin I.R.D.S., but differences in methodology and severityof disease make comparison difficult. In severe I.R.D.S.tubular function as well as glomerular function may bedefective ;5 even when acidotic these infants acidify theirurine poorly, so the urine may be alkaline.What precipitates the renal insufficiency? Hypoxae-

mia, if prolonged, causes oliguria in infants2 in puppies6(paradoxically, short hypoxic episodes inducediuresis’). But from the work of Guignard2 it is clearthat some other factor must diminish renal blood-flow,since Po2 levels were similar in the two I.R.D.S. groupswith disparate renal function; hypercapnia may be moreimportant. 8 Drugs,9 ventilator therapy, 10 andnatriuresisll are also influential; surprisingly, the role ofhypotension in I.R.D.S. is controversial. 12 13 Birth anoxiacan cause renal failure14 15-a factor ignored by theSwiss workers.

Infants with renal failure complicating I.R.D.S. are notreferred for dialysis. 16-19 Either they are regarded as un-suitable, or else the complication is unrecognised or self-limiting. Guignard et al. suggest that it is self-limitingwhere the lungs improve: they found no histological ab-normality in the kidneys of babies who died. If this is

hypovolaemic prerenal failure (and it may be difficult to

1. Simpson, H. in Neonatal Medicine (edited by F. Cockburn and C. M. Dril-lien); p. 201. Oxford, 1974.

2. Guignard, J. P., Torrado, A., Mazouni, S. M., Gautier, E. J. Pediat. 1976,88, 845.

3. Prod’hom, L. S., Choffat, J. M., Frenck, M., Manzoni, M., Relier, J. P., Tor-rado, A. Pediatrics, 1974, 53, 170.

4. Siegal, S. E., Fisher, D. A., Oh., W. J. Pediat. 1973, 83, 8545. Torrado, A., Guignard, J. P., Gautier, E. Helv. pædiat. Acta, 1974, 29, 399.6. Winterborn, M. H., Primack, W. A., Edelman, C. M. Jr., Spitzer, A. Pediat.

Res. 1975, 9, 381.7. Sapir, D. G., Levine, D., Schwartz, W. B. J. clin. Invest. 1967, 46, 369.8. Beguin, F., Dunmhoo, D. R., Quilligan, E. J. Am. J. Obstet. Gynec. 1974,

119, 630.9. Guignard, J. P., Filloux, B., Lavoie, J., Torrado, A. Clin. Pharm. Ther

1975, 18, 401.10. Moore, E. S., Galviz, M. B., Paton, J. B., Fisher, D. E., Behrman, R. E.

Pediat. Res. 1974, 8, 792.11. Cort, R. L. Acta pædiat. scand. 1962, 51, 313.12. Neligan, G. A., Oxon, D. M., Smith, C. A. Pediatrics, 1960, 26, 735.13. Brown, E. G., Krouskop, R. W., Sweet, A. Y. Pediat. Res. 1974, 8, 444.14. Bernstein, J., Meyer, R. J. Pediat. 1961, 59, 657.15. Dauber, I. M., Krauss, A. N., Symchych, P. S., Auld, P A. M. ibid. 1976,

88, 851.16. Manley, G. L., Collipp, P. J. Am. J. Dis. Child. 1968, 115, 10717. Lugo, G., Ceballos, R., Brown, W., Polhill, R., Cassady, G. ibid. 1969, 118,

655.18. Meadow, S. R., Cameron, J. S., Ogg, C. S., Saxton, H M. Archs Dis.

Childh. 1971, 46, 221.19. Griffin, N. K., McElnea, J., Barratt, T. M. ibid. 1976, 51, 459