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must be frequent and regular. Furthermore, manytrivial intercurrent events can produce biochemicalabnormalities of this degree-a fact that greatlycomplicates interpretation of the results. Histologicalexamination of the liver is essential to confirm hepatitisin these animals. Finally, chimpanzees are expensiveand scarce so studies have been done on few animals. A

satisfactory alternative animal has not yet been found:marmosets seem to be susceptible but are not as readilyor as reproducibly infected as chimpanzees.Attempts to display the causal agent(s) by

electronmicroscopy . have been numerous.

Examinations of both serum and liver tissue haverevealed particles ranging in size from 14 to 180 nm,variously reported to resemble parvoviruses,papovaviruses, and paramyxoviruses. None of theseclaims has withstood scrutiny. Another approach isthat adopted by Dr Prince and colleagues, who in thisissue (p 1071) claim to have identified a virus fromchimpanzee liver cell cultures inoculated with NANBinfectious material. Morphological characteristics

suggest that it belongs to a hitherto undescribed class ofanimal virus. Two weeks ago Seto and co-workers9described reverse transcriptase activity in associationwith NANB agent(s). Whether these two researchgroups are looking at the same viruses remains to beseen. Potentially the findings are very important, butthey need to be confirmed and amplified.Although hepatitis A and B are readily identifiable

by serological methods, great difficulties have beenencountered in devising tests for NANB agents. Therehave been claims of success with immunodiffusion,immunofluorescence, counterimmunoelectrophoresis,radioimmunoassay, and ELISA techniques but nonehas proved specific, reliable, or reproducible. Non-specific antibodies such as rheumatoid factor

undoubtedly account for many of the positive resultsreported. We cannot exclude the possibility thatNANB viruses induce little or no antibody production.Alternatively, the existence of a large number ofimunologically distinct NANB viruses might explainmany of the discrepancies hitherto reported. CouldNANB hepatitis be simply due to HBV infection inwhich for some reason the conventional serum markersare undetectable? This notion arose from theobservation of HBV DNA in the serum of chimpanzeesand patients with NANB hepatitis; but Feinstone and. Hoofnagle, 10 reviewing the data, conclude that theepidemiological and other evidence is strongly againstthis hypothesis. They highlight a further trap for theunwary by pointing out that new techniques such asmolecular hybridisation and monoclonal antibodystudies "are subject to the same scientific restrictions ofsensitivity specificity and reproducibility that plaguethe more conventional approaches".

9. Seto B, Coleman WG, Iwarson S, Gerety RJ. Detection of reverse transcriptase activityin association with the non-A, non-B hepatitis agent(s). Lancet 1984; ii: 941-43.

10. Feinstone JM, Hoofnagle JH. Non-A, maybe-B hepatitis. N Engl J Med 1984; 311:185-89.

Even ifwe cannot yet test for NANB hepatitis agents,can we do anything to lessen the risk of itstransmission? Passive immunisation with gamma-globulin is not widely favoured, and the report from DrLever and co-workers on p 1062 actually incriminatesgamma-globulin in the transmission of this type ofhepatitis. Alter and colleagues" have shown that blooddonors with a raised serum alanine aminotransferase

(ALT) are much more likely to transmit NANB

hepatitis than those with normal transaminases: theyestimate that elimination of donations with an ALTgreater than 60 units would prevent 29% of transfusionNANB hepatitis with loss of only 1-6% of donations.This procedure has been adopted in West Germany,but has not yet found favour elsewhere. More attentionhas been directed towards blood products. NANBviruses seem to be inactivated by formalin as well as byheat, and heat treatment is being evaluated bymanufacturers of commercial factor VIII concentratesin the hope that this will reduce or eliminatetransmission of NANB hepatitis. As regards hospitalpatients, clincians might perhaps consider-in view ofthe many parallels with hepatitis B-whether the

precautions taken in managing hospital patients withacute hepatitis B should not be applied equally to thosewith post-transfusion NANB hepatitis.

Haemolytic Uraemic SyndromeSINCE the haemolytic uraemic syndrome (HUS) was

described by Gasser in 1955,1 the association of

haemolytic anaemia, thrombocytopenia, and acute

renal failure has become a well recognised entity.Though commonest in children under the ageof 4 years, it can occur in any age-group and thesexes are equally susceptible. Typically there is a

prodromal illness, lasting an average of 7 days, withgastrointestinal or upper respiratory symptoms. Whenmicroepidemics occur it is not unusual to find a

common infecting organism.2 Familial forms havebeen described3-5 and association with pregnancy andoestrogen therapy has been reported. After a mildupset, usually with diarrhoea, the patient becomesweak, lethargic, and pale. Purpura develops and theurine diminishes in volume and contains protein,erythrocytes, and granular and hyaline casts. Mucosalbleeding is common. A microangiopathic haemolyticanaemia is associated with leucocytosis and

11. Alter HJ, Percell RH, Holland PV, Alling DW, Koziol DE. Donor transaminase andrecipient hepatitis: impact on blood transfusion services. JAMA 1981; 246: 630-34

1. Gasser C, Gautier E, Steck A, Siebenmann RE, Oechslin R. HaemolytischanämischeSyndrom: Bilateral Nierenrinden Nekrosen bei akuten erworbenen haemolytischenAnaemiea. Schweiz Med Wsch 1955; 85: 905-09.

2. Koster F, Levin J, Walker L, et al. HUS after shigellosis. N Engl J Med 1978; 298:927-33.

3. Remuzzi G, Misiani R, Marchesi D, et al. Treatment of the haemolytic uraemicsyndrome with plasma. Clin Nephrol 1979; 12: 279-84.

4. Kaplan BS, Chesney RW, Drummond KN. HUS in families. N Engl J Med 1975, 292:1090-93.

5. Farr MJ, Roberts S, Morley AR, Dewar PJ, Roberts DF, Uldall PR. The haemolyticuraemic syndrome—a family study. Quart J Med 1975; 174: 161-88.

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thrombocytopenia, the blood film showing fragmentedred cells. Hypertension is a feature in 50% of patients,hepatosplenomegaly and purpura in 30-40%, andanuria in 30%. Renal function usually improves in 2-3weeks but may not be normal for several months.

Prolonged oliguria or persisting hypertension,representing severe renal damage, are bad prognosticfeatures.b 6

The kidneys are swollen and haemorrhagic andhistologically the abnormalities range from mesangialand cellular proliferation, crescent formation, andglomerular thrombosis, to fibrinoid necrosis inarteriolar walls. In extreme cases there is corticalnecrosis. The heart, lungs, brain, pancreas, spleen, andadrenal glands may also be the sites of arteriolarthrombosis. The aetiology is not clear but patho-physiologically there are similarities between HUS,the generalised Shwartzman reaction, and thromboticthrombocytopenic purpura.’ Damage to the kidneysand other organs is a direct consequence ofintravascular coagulation, followed by lysis of fibrinand release of fibrin degradation products. A defect inreticuloendothelial activity may be a predisposingfactor. It is probable that in many cases bacterialendotoxins or vasoactive amines are released into thecirculation and either initiate the clotting cascade, withresultant disseminated intravascular coagulation, ordamage the endothelium, starting a localised

coagulation process leading to microthrombosis.Gastroenteric prodromes occur commonly in HUS andcertain strains of coliform organisms capable of

releasing cytotoxins and haemolysins8 have beencultured from the stools in some cases.In 1977 Byrnes and Khurana9 observed that patients

with thrombotic thrombocytopenic purpura went intoremission after repeated infusions of plasma. Remuzziand co-workers’° then reported that venous

prostacyclin (epoprostenol; PG4) activity was

undetectable in patients before but was restored aftertreatment with plasma infusion. Furthermore plasmasamples collected from patients before such treatmenthad a decreased capacity to stimulate PG4 activityfrom exhausted aortic rings of rats and from culturedporcine endothelial cells. They postulated that patientswith HUS lack a plasma factor that stimulates PGL,activity, and this notion has been strengthened byfurther data."’"

6 Gianantonio C, Vitacco M, Mendilaharzu F, Gallo G. The hemolytic uremicsyndrome. Renal status of 76 patients at longterm follow-up. J Pediatr 1968; 72:757-65.

7. Hammond D, Liebermann E. The hemolytic uremic syndrome. Renal corticalthrombotic microangiopathy. Arch Intern Med 1970; 126: 816-22.

8 Karmali MA, Petrie M, Steel BT, Lim C. Sporadic case to HUS associated with faecalcytotoxin and cytotoxin producing Escherichia coli in stools. Lancet 1983; i: 619-20.

9 Byrnes JJ, Khurana M. Treatment of thrombotic thrombocytopenic purpura withplasma. N Engl J Med 1977; 297: 1386-89.

10 Remuzzi G, Marchisi D, Mecca D. Haemolytic uraemic syndrome: deficiency ofplasma factor regulating prostacyclin activity. Lancet 1978; ii: 871-72.

11. Perico N, Schieppati A, Mecca G, Rossi EC, Remuzzi G. Prostacyclin and renaldisease Clin Nephrol 1982; 18: 111-19.

12. Beattie TJ, Murphy AV, Willoughby MLM, Machin SJ, Defereyn G. Plasmapneresisin the haemolytic uraemic syndrome in children. Br Med J 1981; 282: 1667-68.

13 Webster J, Rees AJ, Lewis PJ, Hensby CN. Prostacyclin deficiency in haemolyticuraemic syndrome. Br Med J 1980; 281: 271.

Platelet activation and vascular endothelial damagewould normally be expected to stimulate synthesis ofPGL, but PG4 synthetase can be inhibited by certainlipid peroxidases formed in the course of arachidonicacid metabolism. Although such inhibitors have notconclusively been shown to be present in the plasma ofpatients with HUS, the phospholipid changes in

erythrocyte membranes strongly suggest peroxidativedamage.14 Feeding of oxidised lipid to vitamin-E-deficient pregnant rats will produce a Shwartzman-likereaction, and production of PG4-like substancesfrom the aortas of rats can be reduced if theyare fed with vitamin-E-deficient diets.’S Vitamin E

(a-tocopherol) is a biological antioxidant and cantherefore prevent lipid peroxidation; and some patientswith HUS have a low plasma vitamin E.14 On thisevidence, it seems likely that the plasma of patientswith the HUS has a reduced antioxidant potentialfavouring the selective destruction ofPGIz synthetase,and Powell and co-workers from Melbourne, Brisbane,and Birmingham16 have now reported results of a pilotstudy of vitamin E therapy in children with HUS. 16children with HUS, 10 of them under 4 years old, weretreated with vitamin E. All had typical HUS with astory of diarrhoea followed by haemolytic anaemia,thrombocytopenia, and renal failure. 14 were oliguricand 11 required dialysis. Heparin was given in only 6patients and none received antiplatelet agents or

plasma transfusions. Plasma vitamin E was measuredin 10 and was normal in 9; nevertheless all patientswere given 1000 mg/m2 vitamin E daily for a minimumof one week. All patients survived and all but 1 hadnormal renal function, normal blood-pressure, andabsence of proteinuria 3 months later. Unfortunately,this was not a controlled trial.Over the past 20 years the outlook for patients with

HUS has greatly improved, thanks to better

management of acute renal failure, but the case fatalityrate is still about 6%." Anticoagulation and

fibrinolytic therapy, though widely used, have neverbeen properly assessed. The results of Powell and co-workers 16 look promising and should now be assessedin a controlled trial.

ARE POSTOPERATIVE PULMONARYCOMPLICATIONS PREVENTABLE?

PULMONARY complications after major surgery are stillclinically important. In 1968 Wightman did a prospectivestudy of 785 surgical operations and found that pulmonarytroubles developed in 21% of patients having gastroduodenaland biliary tract operations but in none of those havingthyroidectomy, radical mastectomy, or major amputation.14. O’Regan S, Chesney RW, Kaplan BS, Drummond KN. Red cell membrane

phospholipid abnormalities in the hemolytic uremic syndrome. Clin Nephrol 1981;15: 14-17.

15. Okuma M, Takayama H, Uchino H. Generation of prostacychn like substance andlipid peroxidation in vitamin E deficient rats. Prostaglandins 1980; 19: 527-36.

16. Powell HR, McCredie DA, Taylor CM, Burke JR, Walker RG. Vitamin E treatment ofhaemolytic uraemic syndrome. Arch Dis Child 1984; 59: 401-04.

17. Gianantonio C, Vitacco M, Mendilaharzu F, Gallo G, Sojo ET. The haemolyticuraemic syndrome. Nephron 1973; 11: 174-92.

1. Wightman JAK. Prospective survey of the incidence of postoperative pulmonarycomplications. Br J Surg 1968; 55: 85-91.