1313

several aspects of vitamin A behaviour in blood encouragedusl to propose that circulating concentrations are

influenced by the acute phase response (APR). Thoseobservations, and the numerous reports suggesting thatvitamin A supplements diminish morbidity in the

developing world, led to the suggestion that the vitaminmay act by downregulating the APR.A common link in the metabolism of retinol and iron is

the fact that both substances are transported by the"negative" acute phase proteins, retinol binding proteinand transferrin-ie, proteins whose synthesis is depressedby infection. Iron deficiency anaemia is undoubtedlywidespread in the developing world,2 but so too is infection.All physicians are familiar with the anaemia of chronicinfection, and it seems plausible that chronic respiratoryand gastrointestinal infection plays a part in the aetiology ofso-called nutritional anaemias.

Acute phase responses are generally thought to be

beneficial, but what are the beneficial effects of depressingvitamin A and iron in the circulation in the presence ofinfection? One very rapid response to infection is anincrease in endothelial permeability, so perhaps thereduced synthesis of small molecular weight proteins suchas retinol binding protein, transferrin, and albumin is ashort-term measure to reduce urinary losses of these

compounds. Moreover, in patients with tissue damageassociated with chronic infection, low concentrations ofcirculating iron may protect tissues by lessening the

pro-oxidant effects of iron. By contrast, low concentrationsof circulating retinol, especially in growing children orpregnant women, may have adverse effects. More and morestudies in which ocular impression cytology has been usedhave found evidence of epithelial abnormalities associatedwith low, but not necessarily deficient, retinolconcentrations. 4,5

Thus, low retinol concentrations, in the long term, do notseem to offer any biological advantage but their widespreadoccurrence in the third world may be a feature of theoverwhelming presence of infection; and retinol, like iron 7

may be trapped within the liver. Iron accumulation in liverand spleen is a common response to chronic infection andthe accompanying depression of the retinol bindingprotein/retinol complex may further exacerbate theinfection. This vicious cycle can be broken byadministration of oral vitamin A, as has been shown insevere measles.8 The anti-infective properties of vitamin Aare widely acknowledged and suppression of infectionwould immediately stimulate a resumption of transferrinand retinol binding protein synthesis, thereby releasing thetrapped iron and retinol.Suharno et al report that women with clinical

manifestations of chronic or infectious disease were

excluded from the trial; this suggests that vitamin A was notacting as an anti-infectious agent. However, their subjectswere villagers from middle and low socioeconomic groupswho would be constantly exposed to poor sanitation,contaminated food and water, and a high burden ofinfectious disease. As judged by plasma retinol, only 11 % ofthe women had marginal vitamin A status ( < 0,7 Ilmol/L)but the mean baseline value was only 1-08 umol/L. In otherparts of the world, such values in children are associatedwith a high proportion of ocular impression cytologyabnormalities;5 they may therefore be insufficient for therequirements of mother and fetus, particularly in suchenvironments. Experimental studies have shown that

tissues such as the eye, gut, and respiratory tract areespecially susceptible to vitamin A deficiency, and anyimpairment in epithelial integrity will allow bacteria whichare normally present to invade and colonise. The low retinolconcentrations in these women may also have worsenedtheir burden of low-grade opportunistic infections, butpresumably these responded to the vitamin A treatment.

Suharno and colleagues show the effectiveness ofcombined vitamin A and iron treatment in removing 97 % ofthe anaemia in the pregnant women. Iron treatment alone

produced double the effect of vitamin A, so iron could beregarded as more cost effective. However, other workershave not been so successful with iron alone and the reasonsfor the success in this study are not immediately obvious.Another concern is that the pro-oxidant effects of ironmight exacerbate tissue damage in chronic or infectiousdisease, and in malarious areas iron therapy has beenassociated with increased levels of infection.9 If the vitaminA element of combination treatment depresses infectionand thereby restores the integrity of epithelial tissues, thedamaging effects of iron may well be clinically insignificant.

David I ThurnhamHuman Nutrition Group, Department of Biology and Biomedical Sciences, University ofUlster at Coleraine, Londonderry, Northern Ireland

1 Thurnham DI, Singkamani R. The acute phase response and vitaminA status in malaria. Trans R Soc Trop Med Hyg 1991; 85: 194-99.

2 DeMaeyer EM, Adiels-Tegman M. The prevalence of anemia in theworld. World Health Stat Q 1985; 38: 302-16.

3 Shearman CP, Gosling P. Microalbuminaemia and vascularpermeability. Lancet 1988; ii: 906-07.

4 Udomkesmalee E, Dhanamitta S, Sirisinha S, et al. Effect of vitaminA and zinc supplementation on the nutrition of children in NortheastThailand. Am J Clin Nutr 1992; 56: 50-57.

5 Resnikoff S, Filliard G, Carlier C, Luzeau R, Amedee-Manesme O.Assessment of vitamin A deficiency in the Republic of Djibouti. EurJ Clin Nutr 1992; 46: 25-30.

6 Coutsoudis A, Broughton M, Coovadia HM. Vitamin Asupplementation reduces measles morbidity in young African children:a randomised, placebo-controlled, double-blind trial. Am J Clin Nutr1991; 54: 890-95.

7 Mejia LA, Hodges RE, Rucker RB. Role of vitamin A in absorption,retention and distribution of iron in the rat. J Nutr 1979; 109: 129-37.

8 Hussey GD, Klein M. A randomized, controlled trial of vitamin A inchildren with severe measles. N Engl J Med 1990; 323: 160-64.

9 Smith AW, Hendrickse RG, Harrison C, Hayes RJ, Greenwood BM.The effects on malaria of treatment of iron-deficiency anaemia withoral iron in Gambian children. Ann Trop Paediatr 1989; 9: 17-23.

Medicine on the superhighway

Information is like a smash-hit play: you know it exists, youbelieve the experience will be life-enhancing, but youcannot gain access. With the advent of computer networks,many more tickets to the information theatre have becomeavailable. The full potential of computer networks isrealised in their interconnection via telecommunications

links, with resulting information "highways". Thus, atleast in theory, network users anywhere in the world canexchange data with one another.

Technical considerations mean that networks have beenlimited to handling data in the form of text, because

graphics and moving images contain far too many bits ofinformation to be transmitted in any useful time frame. But

technology moves on, and simultaneous text, graphics,moving pictures, and sound are now a possibility on somevery high-capacity networks such as NREN (NationalResearch and Educational Network) in the USA and

SuperJANET (super Joint Academic Network) in the UK.

1314

SuperJANET, which has been developed with C5 millionof British government money and will soon link fiftyuniversity sites in the UK, can handle data at 140

megabits/second-eg, a 5500 page document in 1 second.This is a 70-fold increase in capability over the existingJANET network. NREN is intended to link research andeducational sites throughout the USA, and will eventuallybe even more capable than Super JANET, with a plannedcapacity of over 600 megabits/second. Similar high-capacity networks are planned for much of Europe, and indue course the worldwide network of networks (known asInternet) will probably conform to the high-capacitystandard, becoming an information "superhighway".How might high-capacity computer networks change the

way doctors work? For any procedure that involves visionor sound (eg, monitoring the progress of anaesthesia, orgiving an opinion on a biopsy slide, fetal ultrasound, orcomputed tomography scan)-and potentially even

touch-the physician need no longer be present in the sameroom, or even in the same country, as the patient orspecimen. Experiments with electronic transmission ofimages to doctors (telemedicine) have been going on sincethe early 1900s. Framework for European Services in

Telemedicine (FEST) is a European Community fundedproject intended to set standards and provide guidelines fortelemedicine throughout the continent. One of the projectsstudied by the FEST collaborators involves transmittingradiographic images and electrocardiograph traces fromremote Greek islands to Athens for interpretation byspecialists. The technology is far more basic than with

high-capacity computer networks: the images are digitisedwith a video camera connected to a personal computer andthen sent to Athens via public telephone lines. Althoughthis approach is cheap and a big advance on having nospecialist advice available, the long-term future oftelemedicine surely lies with high-capacity computernetworks beause of their ability simultaneously to handledata in a variety of formats (multimedia).What are the practical medical applications of a high-

capacity network such as SuperJANET? Imagine a

histopathologist being given a bone-biopsy sample from apatient with a suspected bone tumour. Before making adiagnosis, which may profoundly influence management,the pathologist decides to seek a second opinion. He contactsa colleague hundreds of miles away, and through thecomputer network both individuals can view on their

desk-top terminals an image of the sample generated by avideo camera attached to the microscope. Not only that, theycan speak to one another, use a "pointer" to highlight areasof interest on the screen, and see a moving picture of eachother if they so wish. Remote consultation is just one ofmany potential applications of high-capacity networks.Other possible uses, all of which were demonstrated to ameeting at the Royal Postgraduate Medical School,London, on November 9, include dissemination of graphicalteaching aids, retrieval of magnetic resonance and positronemission tomography images from distant databases, anddrug modelling, in which the image is formed on the screenof a desk-top work station while processing takes place in asupercomputer many miles away.The issue that will have to be resolved before high-

capacity networks come to be used in routine medicalpractice is mainly one of cost. Development and installationof computer networks has largely been funded bygovernment and institutions; service providers, if they

charge at all, claim a connection cost rather than a fee peruse. Thus networks appear free to the user, an attractionthat encourages their use. Consequently, doctors who haveaccess will probably begin to use SuperJANET and NRENroutinely, even though these networks are intended forresearch purposes. A charge for routine medical use mayhave to be introduced in the early days of high-capacitynetworks to avoid the trouble that would arise if the medical

community was suddenly asked to pay for a service onwhich it has come to depend. Perhaps governments, havingpaid the initial costs, will ask health-care providers to fundfurther network development and installation. Access tosuch networks will have to be carefully controlled to

safeguard confidential information. Meanwhile, as high-capacity computer networks become an accepted part ofmedical practice, let us hope that the day never comes whenthe only contact between doctor and patient is through acomputer terminal.

John McConnellThe Lancet, London, UK

Balloon sphincteroplasty vs endoscopicpapillotomy for bileduct stones

Endoscopic papillotomy is the standard non-surgicalmethod for removal of bile duct stones.1 Introduced in 1974,this electrosurgical technique allows the operator to incisethe papilla and surrounding sphincter muscle so thatcommon bileduct stones may be retrieved directly bybasket, be pushed through by balloon, or pass

spontaneously along the incision, which is usually10-15 mm in length. Experienced operators achieveclearance of the biliary tree in 80-90% of cases, with majorcomplications (bleeding, perforation, or pancreatitis) in

10% or less.’Endoscopic papillotomy is used increasingly in young

individuals to clear the bileduct of stones before

laparoscopic cholecystectomy. However, as many as 10% ofthese patients will develop stenosis, new stones, or bothafter the procedure; most such cases can be treated

endoscopically and will not require surgery.2MacMathuna and colleagues3 have now advocated

endoscopic balloon spincteroplasty as a safe alternative topapillotomy for removal of bile duct stones. This techniqueconsists of balloon dilation of the papilla (two dilations ateight atmospheres to a maximum diameter of 1 cm for 60 s),after which a basket, retrieval balloon, or mechanical

lithotriptor is used for stone extraction. In twenty-eightpatients in whom this technique was used, the success ratefor bileduct clearance was 79%, there were no cases ofbleeding, and pancreatitis was seen in only one patient,resolving within 24 h. Because the ampulla is not cut butonly transiently dilated (which causes me to question theuse of the term sphincteroplasty, which implies a lastingalteration), no long-term complications were anticipated.The procedure is said to be easy to learn and requires less

operator skill than endoscopic papillotomy. The relativedifficulty of stone extraction following dilation cannot beascertained from this study. Moreover, no short-term (oneyear) follow-up information was provided, so the truefailure rate cannot be assessed. At one year the true failurerate might exceed 21% if we were to include earlyrecurrences-which are likely to be due either to stones notcleared at the time of the procedure itself or to stones that