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organisms from his stools, the patient was isolatedwith a tentative diagnosis of plague. But the diagnosisQf plague could not be substantiated, and, when thepatient died of haemorrhages, necropsy revealed a

fulminant hepatitis.Those investigating the case-notably Prof. J. H. S.

Gear-suspected Lassa fever from the clinical signsand symptoms. i-6 The lesions 4 in liver, spleen, andkidneys were consonant with this diagnosis and seemedto rule out infectious hepatitis, Rift Valley fever, andall other types of liver necrosis with haemorrhage; andthere was evidence that the patient had been heavilyexposed to the rodent reservoir of Lassa fever, Masto-mys natalensis, in the Wankie region of Rhodesia. Butconfidence in the diagnosis of Lassa fever was shakenwhen the Center for Disease Control, in Atlanta,Georgia, reported that the virus isolated bore moreresemblance to Marburg virus 6-8 than to Lassa virus-a conclusion supported by the local virologicalinvestigations. The patient’s conjunctivitis,, photo-phobia, and lymphadenopathy were compatible withthis diagnosis and there was evidence that he had beenbitten in Rhodesia by an unidentified insect or animalwhich inflicted three puncture wounds with flares-

though the lymphadenopathy was not in the drainageareas of the puncture wounds. The neurologicalcomponents of the Marburg virus disease were

absent, and the incubation period, difficult to establish,seemed longer than expected.

If these cases are Marburg virus disease they willbe the first recognised since the original outbreaksin Germany and Yugoslavia in 1967, which weretraced to vervet monkeys (Cercopithecus aethiops)imported from Uganda. Serological investigationsin the Lake Kyoga area have shown that Marburgvirus can infect both monkeys and man withoutproducing overt illness.9 Antibody to Marburg virushas been detected in baboons in Kenya 6 but not inbaboons or vervet monkeys in South Africa whereextensive surveys were made by Strickland-Cholmleyand Malherbe.10,ll These workers, in reporting thattheir own researches on the Marburg agent had to beterminated, warned that they " cannot predict whereit may next be encountered" .10 It will be ironic if it is

proved to be next encountered in their home city.A full description of this disease outbreak is urgentlyneeded. There are some anomalous features whichraise the possibility that it may be a hitherto undes-cribed infection; to the Marburg virus we may have toadd a Jo’burg virus. Meanwhile, it is extremely fortu-nate for South Africa, and perhaps for other countries,

1. Lancet, Feb. 15, 1975, p. 376.2. Carey, D. E., Kemp, G. E., White, W. A., Pinneo, L., Addy, R. F.,

Fom, A. L. M. D., Stroh, G., Casals, J., Henderson, B. E. Trans.R. Soc. trop. Med. Hyg. 1972, 66, 402.

3. White, H. A. ibid. p. 370.4. Frame, J. D., Baldwin, J. M., Cocke, J., Troup, J. W. Am. J. trop.

Med. Hyg. 1972, 19, 670.5. Monath, T. P., Mertens, P. E., Patton, P. E., Moser, C. R., Baum,

J. J., Pinneo, L. J., Cary, G. W., Kissling, R. E. ibid. 1972, 22, 773.6. Monath, T. P. WHO Chron. 1974, 28, 212.7. Martini, G. A. Postgrad, med. J. 1973, 49, 542.8. Murphy, F. A., Simpson, D. I. H., Whitfield, S. G., Zlotnik, I.,

Carter, G. B. Lab. Invest. 1971, 24, 279.9. Gordon Smith, C. E. in The Scientific Basis of Medicine; p. 58.

London, 1971.10. Strickland-Cholmley, M., Malherbe, H. Lancet, 1970, i, 476.11. Strickland-Cholmley, M., Malherbe, H. in Marburg Virus Disease

(edited by G. A. Martini and R. Siegert); p. 195. Berlin, 1971.

that the patients were treated in one of the country’sleading teaching hospitals and that facilities for expertvirological diagnosis and investigation were to hand.

COMPUTERS NOW

WHEN the N.H.S. computer programme began inthe late ’60s, not everyone thought that the way wouldbe long, difficult, and very expensive-but this is howit is proving. Provisional estimates 1 suggest that inthe year 1974-75 expenditure by regions on computersfor day-to-day service purposes will be E7 million,whereas the computer R. & D. programme, which is

centrally funded and organised, will have cost E4million ; this ratio is itself an indication of how slow

progress has been, especially since regional authoritieswere using computers for some purposes long beforethe research programme got under way. Several

things have gone wrong. Many projects are behindschedule (" slippage " is the Department’s more

delicate term); some, including one or two big ones,have failed; and computer staff are so difficult to findthat a quarter of established posts are unfilled. Earlyoptimistic projections are now seen to have been

unrealistic, and critics who learn that one majormedical-records project was later abandoned by thehospital, and that monitoring in intensive-care units isbetter left with the nurses,2 are now saying " We toldyou so ". Reviewing progress with the whole pro-gramme, Rivett 3,4 admits that " the proponents ofmedical computing have been over-optimistic in theirpredictions, and we have not yet emerged from thephase of cynicism which has followed ". For tworeasons N.H.S. computing research needs especiallystrict scrutiny. It is, by any standards, expensive.Secondly, by a deliberate act of policy, some of theuncertainty that both stimulates and frustrates mostscientific research is excluded. "... those concernedwith policy, " writes Rivett 4 " must accept that ECGanalysis is worth exploring before such an experimentis launched." Other computer users must hope that theDepartment’s poor response to this particular applica-tion 5 is atypical.The objectives are straightforward enough: those

in the N.H.S., whether as health workers or admini-strators, want to know if a particular application ofcomputers to aspects of the Service’s labour-intensivework is feasible and cost effective and if, after this

period of evaluation, the application is transferablefor general use in the regions. The Department hasrightly adopted a policy of computer standardisationto simplify transfer; but, equally properly, the

decision, the choice between, say, a computer and anew health centre, is left to the health authorities.But how scientific is this evaluation ? Some resultsfrom the very important clinical-chemistry projectsare expected this year, and these results should be in aform from which cost-benefit decisions can be made.Where input is less numeric, evaluations are likely to

1. D.H.S.S. Annual Review of National Health Service Computing1974: part I, tables A-C.

2. Lancet, 1974, ii, 877.3. Rivett, G. C. Hlth Trends, 1975, 7, 5.4. Rivett, G. C. ibid. p. 9.5. Lancet, 1974, ii, 505.

734

prove much more subjective. Before-and-after experi-ments are difficult to interpret: organisations andpractices change while the experiment is going on,and the experiment itself may have effects beyond thestrict remit of the trial but still important to the finalevaluation. For example, if a laboratory offers a

speedier results service, clinicians may send down

blood-samples they previously would not havebothered to collect. Controlled trials have theirdifficulties too, but it is hard to see how the problemsare any greater than those faced by evaluators of

screening or other health-care research. A computerprogramme may be applied research, technology,customer/contractor research-call it what you will-but this does not make a scientific evaluation and

presentation of the results any less appropriate.Statements of what the computer R. & D. programme

now costs do not tally 1,6 but if the Medical ResearchCouncil’s transferred funds are left out of the calcula-tions, on the grounds that transfer is still a paper trans-action, then the programme uses up a quarter of allDepartmental R. & D. money. Control is in thehands of a well-staffed computer division which is

essentially administrative since it does not yet have itsown computers and technical services. Guidancecomes from an advisory committee, and the programme,theoretically though not hierarchically, comes underthe Chief Scientist’s Organisation. Customer/con-tractor research is concerned with practical problems,and it is on the usefulness of the results that projectsare judged. But there are lessons to be learned fromfailures too, and is a tragedy that postmortems onthe King’s and Addenbrooke’s/Bart’s failures are

not to be made public. The Department of Health’sown R. & D. funds have grown from next to nothingin the early ’60s to E10 million in 1972-73 and E19million in the year just ending. 6 This allocationcannot for long retain its apparent immunity fromcutback, yet the Computer Division is even now

committed to spending at least t5 million a year atthe end of the decade. 1975 might be a good timefor a thorough and independent look at the way thingsare going; the Department’s annual reviews givemore information than is to be found in many other

reports from research organisations, but an internalaudit is not enough.

NALOXONE

NALoxoONE is the N-allyl derivative of the narcoticanalgesic, oxymorphone. In common with other N-

allyl narcotic derivatives, such as nalorphine andlevallorphan, it possesses narcotic antagonist proper-ties. But naloxone differs from these derivatives intwo important respects-it has no agonist or intrinsicnarcotic activity and it is the only specific antagonistto pentazocine. Since the first report of its antagonistactivity in man the pharmacology has been exten-sively investigated. It is best given parenterally,activity being low after oral dosage. Injected intra-venously, it acts within one or two minutes, and the

6. D.H.S.S. Annual Report on Departmental Research and Develop-ment 1974. H.M. Stationery Office, 1975.

7. Lunn, J. N., Foldes, F. F., Moore, J., Brown,I. M. Pharmacologist,1961, 3, 66.

half-life is about twenty minutes. The brevity of itsaction is probably due to rapid metabolism in the liver. 9An intravenous dose of 0-4 mg. reverses the actions

(including analgesia) of relatively large doses of

narcotics, 8 but with the longer-acting narcoticsfurther doses may be needed. Given alone, naloxoneaffects neither ventilation nor pupil size and there areno sedative or psychomimetic side-effects.10 Clinically,the main applications are likely to be in nsthesia, inmanagement of drug overdose and drug abuse, andin obstetrics.

.

In anaesthesia, narcotics, often in large doses, areused to supplement nitrous oxide. Such regimensmay give rise to postoperative sedation and ventilatorydepression, and these can be controlled with naloxone.Because a large dose may violently arouse the patient,the drug is best given in small intravenous increments,of 0.1 mg. perhaps, so as to obtain a suitable balancebetween reversal of ventilatory depression and main-tenance of analgesia. An unconscious or drowsypatient who has taken an overdose of drug can besafely given naloxone as a therapeutic test. An in-crease in ventilation and conscious level, especiallyif accompanied by an increase in pupil size, isevidence of narcotic depression. When narcoticoverdose is treated with naloxone the patient shouldbe observed for a return of ventilatory depression,whereupon additional naloxone should be given."The duration of action can be increased if thenaloxone is given by intravenous infusion or intra-muscular injection. In narcotic addicts naloxoneproduces signs of withdrawal and pupillary dilatation,and it has replaced nalorphine for detection of narcoticdependence.12 Again the doses should be small, sinceintravenous naloxone can precipitate a severe with-drawal syndrome in dependent addicts. An especiallyinteresting application has been in the treatment

of addicts by large oral doses-up to 3000 mg.daily-to block the effects of narcotic administration. I IThe possibility that addicts could be rendered in-sensitive to narcotics for a long period by a parenteraldepot preparation of naloxone is being examined.In obstetrics not much work has yet been done on this

agent. When given to the neonate at birth, naloxonereverses the depressant effects of narcotic analgesicswhich the mother received during labour. 14 Unlike

nalorphine, it probably does not increase depressioncaused by hypoxia, acidosis, or other drugs.

Interest in naloxone has not been confined to theclinical sphere. Using tritiated naloxone, Pert andSnyder 15 have made a major advance in the identifica-tion and understanding of narcotic receptors inmammalian tissues. Their findings are of greatfundamental value and are likely to have far-reachingpractical applications in the study of new narcoticdrugs.8. Evans, J. M., Hogg, M. I. J., Lunn, J. N., Rosen, M. Br. med. J.

1974, ii, 589.9. Weinstein, S. H., Pfeffer, M., Schor, J. M., Franklin, M., Mints, M.,

Tutko, E. R. J. pharm. Sci. 1973, 63, 1416.10. Evans, J. M., Hogg, M. I. J., Lunn, J. N., Rosen, M. Anæsthesia,

1974, 29, 721.11. Evans, L. E. J., Roscoe, P., Swainson, C. P., Prescott, L. F. Lancet,

1973, i, 452.12. Blatchly, P. H. J. Am. med. Ass. 1973, 224, 334.13. Zaks, A., Jones, T., Fink, M., Fredman, A. M. ibid. 1971, 215, 2108.14. Evans, J. M., Hogg, M. I. J., Rosen, M. Proceedings of 4th European

Congress of Anæsthesiology, 1974 (in the press).15. Pert, C. B., Snyder, S. H. Science, 1973, 179, 1101.