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not always.9 At a colloquium in Edinburgh on Feb.2, devoted to Alzheimer’s disease, plans to assessthe value of choline and of lecithin in this varietyof dementia found favour, since there is pharmaco-logical evidence that learning involves cholinergicpaths and is enhanced by such treatment in normalsubjects." In Alzheimer’s disease, reduced activityof enzymes concerned with acetylcholine is foundin cerebral cortex and especially in the hippo-campus." With choline the best prospect of im-provement would presumably be in the younger pa-tients with early disease. Vasopressin and relatedpeptides may also now lay claim to consideration;if a trial is mounted, it should be on patients of thistype.

THE GENERAL PRACTITIONERS’ CASE

IN 1977 the Conference of Representatives of LocalMedical Committees called for "a completely newcharter to be negotiated to ensure that the average netremuneration of a general practitioner be comparablewith the medical remuneration in countries in theEEC". From this resolution emerged the report (see p.432) published this week by a working party establishedby the General Medical Services Committee and led byDr J. G. Ball. The recommendations will be discussed atthe next L.M.C. conference in June.Though the prescription for their task seemed to call

for a pay claim based on comparability studies withWest German doctors, the working party has not pro-nounced on actual money. The proposed formula isbased on the existing "modified capitation" system witha much extended range of services for which the generalpractitioner would be paid a fee. The Review Body’s rolewould be to assess "average net remuneration" on thebasis of the limited services covered by the workingparty’s "basic commitment payment". And all else, in-cluding activities outside normal working hours, wouldbe paid for separately-as a kind of productivity deal.The argument is that "with no ceiling on demand thereis no justification for a ceiling on payment".As they debate the charter and its contract, general

practitioners will applaud the emphasis on the improve-ment of standards, and particularly in the inner cities;and few will dispute the need for self-monitoring by pro-fessional audit. They will agree that all the officialenthusiasm for preventive medicine has not been ade-quately reflected in better resources for primary care.They would be right to have misgivings, however, aboutthe view that progress and freedom can be best achieved

by a "more overtime" structure and by a vast extensionof the fee-for-service compendium. Therein lie a furtherwithdrawal from the long-respected role of the familydoctor and the prospect of cumbersome and expensiveadministrative additions to dispense and regulate allthese payments. Moreover, even at a modest pricing, thecontract outlined in the charter could cost the N.H.S.

Blake, D. R., Dodd, M. J., Grimley Evans, J. ibid. 1978, i, 608.10 Sitaram, N., Weingartner, H., Gillin, J. C. Science, 1978, 201, 274.11 Davies P, Maloney, A. J. F. Lancet, 1976, ii, 1403.

far more than any Government, whatever the dramaticE.E.C. comparisons, would be prepared to supply. Thechallenge to the draft charter lies in the contention thatthe wiser and more realistic course would be to pursuethe general practitioners’ reasonable claim without in-voking the complexities of more overtime and more fees-for-service.

TUBAL RELIEF OF MALIGNANT BILEDUCTOBSTRUCTION

THE non-surgical approaches to extrahepatic obstruc-tive jaundice include endoscopic diathermy sphincter-otomy,’ which is of greatest value for stones in the com-mon bileduct and for papillary stenosis, and wire-basketextraction of gallstones along the track of a T-tube,2 2which is useful after cholecystectomy. The advantage ofthese non-operative methods is said to be that conven-tional surgical exploration (or re-exploration) in suchpatients has a high mortality and morbidity, though no-one has satisfactorily compared the results of such tech-niques with those of specialist surgical management. 3Another non-surgical method, this time for the relief ofmalignant obstructive jaundice, has lately been de-scribed by Pereiras et al. Their technique, which theyreport in twelve patients, is a development from thewell-established percutaneous trans-hepatic cholangi-ography of Okuda5 which employs the Chiba (or"skinny") needle. After percutaneous cannulation of abileduct the malignant duct stricture is dilated underlocal anxsthesia by a series of catheters passed over aguide wire, the largest catheter finally being used to im-pact an indwelling ’Teflon’ prosthesis of 12 french

gauge. The efficacy of the drainage procedure is con-firmed radiographically by free passage of contrastmedium from intrahepatic ducts into the duodenum.The follow-up was only 4-30 weeks, but the patientshad advanced malignant disease. Pruritus was alwaysrelieved and jaundice disappeared in all but two. Exter-nal tube drainage may be required for a few days. Twopatients died within a week from complications of theirmalignant jaundice. This method of intubation deservesto be added to existing techniques for short-term decom-pression of a dilated biliary tree, particularly in thepoor-risk patient with advanced malignant obstructionof the major extrahepatic ducts. With very little upset tothe patient, the remaining months of life may be mademore comfortable.

AVAILABLE OXYGEN IN PRETERM BABIES

FETAL haemoglobin is excellent stuff for the fetus, andin the infant born at term its gradual fall in concentra-tion6 from 70-80% to about half of this at two monthsof age suggests that there is no need for hurry in the

1. Safrany, L. Lancet, 1978, ii, 983.2. Burhenne, H. J. Radiology, 1974, 113, 567.3. Blumgart, L. H., Wood, C. B. Lancet, 1978, ii, 1249.4. Pereiras, R. V. Jr., Rheingold, O. J., Hutson, D., Mejia, J., Viamonte, M.,

Chiprut, R. O., Schiff, E. R. Ann. intern. Med. 1978, 89, 589.5. Okuda, K., Tanikawa, K., Emura, T., Kuratomi, S., Jinnouchi, S., Urabe,

K., Sumikoshi, T., Kanda, Y., Fukuyama, Y., Mush, H., Mor, H., Shi-mokawa, Y., Yakushi, I. F., Matsuvra, Y. Am. J. dig. Dis. 1974, 12, 21.

6. Garby, L., Sjölin, S., Vuille, J-C. Acta pœdiat. 1962, 51, 245.

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transition. The high affinity which fetal blood has foroxygen’ is ideally suited to transfer of oxygen across thelow gradient from maternal to fetal circulation. Deliveryof oxygen from fetal blood to the tissues is assisted bythe greater quantity of red blood-cells and higher hxmo-globin concentration that are found in the circulationbefore birth. In the event of a precarious delivery theacidosis which develops in an asphyxiated infant shiftsthe oxygen-dissociation curve to the right and allowssome of the increased tissue demands to be met. The pos-ition of the oxygen dissociation curve in the newborn is

greatly affected by the proportion of adult hxmoglobinin the blood since the oxygen affinity of adult, but notfetal, hxmoglobin is greatly reduced by combinationwith red-cell organic phosphates, notably 2,3-diphos-phoglycerate (2,3-D.P.G.). Were the switch in productionfrom fetal to adult haemoglobin to be delayed it seemsthat most individuals would come to no harm, since per-sistence of fetal haemoglobin in some persons with homo-zygous thalassaemia has permitted healthy survival intoold age.8

In the preterm infant, and particularly the severelypreterm, the high oxygen affinity of fetal blood can haveserious consequences. During episodes of respiratory-dis-tress syndrome it has been suggested that exchangetransfusion with fresh adult blood may be life-saving,9provided the oxygen tension in the infant’s blood can beraised to 50-60 mm Hg by mechanical ventilation. Apaper from the University Hospital of Walesl0now sug-gests that during the so-called physiological anaemia ofprematurity infants may in fact be at a serious disadvan-tage because of the low availability of oxygen in theirblood. The early anaemia of prematurity reaches its low-est point at 3 to 7 weeks of age." Its cause is controver-sial but, unlike the late anaemia which appears at 3 to4 months, it is not related to iron deficiency. The mainfactors seem to be the rapidly expanding plasma volumeof the preterm infant, the shortened life of the erythro-cyte, and hypoplasia of the bone-marrow.1;2 Erythropoie-tin can be detected in the plasma at this time and corre-lates inversely with the "oxygen-releasing capacity" ofthe infant’s blood as calculated from 2,3-D.P.G. and fetalhaemoglobin concentrations 13 Apart from its possible rolein stimulating erythropoietin production there is noknown benefit from the early anaemia of prematurity,and it can be regarded as physiological only in the sensethat it arises to some extent in all preterm babies. War-

drop and others5 have compared clinical features in aseries of preterm infants with measurements of their"available oxygen", an expression which they derivefrom haemoglobin-oxygen affinity (P50) and haemoglobinconcentration and which represents the amount of

oxygen per unit of blood that is capable of release to thetissues. They found that infants of up to 32 weeks’ ges-tation with clinical evidence of anxmia had smaller

7. Darling, R. C., Smith, C. A., Asmussen, E., Cohen, F. M. J. clin. Invest.1941, 20, 739.

8. Weatherall, D. J., Clegg, J. B., Wood, W. G. Lancet, 1976, ii, 660.9. Delivona-Papadopoulos, M , Roncevic, N. P., Oski, F. A. Pediat. Res. 1971,

5, 235.10. Wardrop, C. A. J., Holland, B. M., Veale, K. E. A., Jones, J. G., Gray,

O. P. Archs Dis. Childh. 1978, 53, 855.11. O’Brien, R. T., Pearson, H. A. J. Pediat. 1971, 79, 132.12. Gairdner, D, Marks, J., Roscoe, J. D. Archs Dis. Childh. 1955, 30, 203.13. Stockman, J. A., Garcia, J. F., Oski, F. A. New Engl. J. Med. 1977, 296,

647.

amounts of available oxygen than did symptomless in-fants, but clinical anxmia correlated less well with

depression of either haemoglobin or P50 alone. Unfor-tunately the definition of their study group is not consis-tent and this conclusion is apparently based on only apart of the group originally defined. With this limitationtheir data must be accepted as having an importantbearing on the management of the severely preterm in-fant. They show that "available oxygen" has a linearcorrelation with gestational age and can therefore becalculated from a simple formula if age and haemoglobinconcentration are known. The clinical signs which theCardiff group held to be suggestive of anaemia includedfeeding difficulties, dyspnoea, tachypnoea, tachycardia,diminished activity, and pallor. In 17 of the 18 preterminfants who were given blood on account of these symp-toms transfusion was followed by a decrease in heartrate, respiratory rate, or both. Several had haemoglobinconcentrations which would conventionally have beenregarded as within the normal range.

Provided that care is taken to avoid overload of the

circulation, risks from transfusion in the newborn areprobably slight, though the need for fresh blood must in-crease the chance of virus transmission. Stored bloodcarries the usual risks for the newborn and also hampersgas transfer. 14 The iron content of the transfused bloodis likely to be a bonus although aspects of the work ofBullen et al.15 suggest theoretical disadvantages.Humoral immune factors in the plasma may well bebeneficial and it would be of interest to examine somesuch index of infection as nasal swabs or stool flora in

recipients of early blood-transfusions. New ideas are sel-dom so acceptable as when they give support to old prac-tices, and consideration of the availability of oxygen inthe blood of preterm infants may go some way towardsvindicating a distinguished American pxdiatrician whoon a Sunday morning ward-round in the 1920s is said’6to have ordered seven transfusions when he had only 6patients.

ANTI-INFLAMMATORY DRUGS AND TUMOURGROWTH

MOST, if not all, anti-inflammatory drugs inhibit pro-staglandin synthesis 1,2 and phosphodiesterase activity.3 3Prostaglandins and cyclic nucleotides have been impli-cated in many aspects of tumour development andgrowth. So it would not be surprising if anti-inflamma-tory drugs influenced the growth and spread of tumours.Unfortunately, much of the experimental evidence is

confusing and contradictory.The experimental evidence in the main indicates that

prostaglandin E (P.G.E) and cyclic A.M.P. will inhibit thein-vitro replication of normal, transformed, and malig-nant cells.4-6 Prostaglandin F (P.G.F) and cyclic G.M.P.do not, and often have the opposite effect of stimulating

14. Valtis, D. J., Kennedy, A. C. Lancet, 1954, i, 119.15. Bullen, J. J. Rogers, H. J., Leigh, L. Br. med. J. 1972, i, 69.16. Taussig, H. B. Pediat. Res. 1971, 5, 569.1. Vane, J. R. Nature New Biol. 1971, 231, 232.2. Hong, S. L., Levine, L. Proc. natn. Acad. Sci. U S.A. 1976, 73, 1930.3. Kuehl, F. A., Ham, E. A., Zanetti, M. E., Sanford, C. H., Nicol, S. E., Gold-

berg, N. D. ibid. 1974, 71, 1866.4. Johnson, G. S., Pastan, I. J. natn. Cancer Inst. 1971, 47, 1347.5. Polgar, P., Taylor, L. Biochem. J. 1977, 162, 1.6. Kurtz, M. J., Polgar, P., Taylor, L., Rutenburg, A. M. ibid. 1974, 142, 339.