1590

10w.1O In our experiments, infusion of indomethacin (at a

concentration that has been shown to reduce prostaglandin releasein perfused placental lobules,") and mepacrine and BW755C (atconcentrations that have been shown to inhibit eicosanoid synthesisin other tissues7,9) failed to increase vascular resistance. In contrast,inhibition of the effects of NO, by NOLA, methylene blue, oroxyhaemoglobin, was associated with a striking increase in vascularresistance. These observations, together with that showing thatsodium nitrite (which mimics the action of endothelium-derivedNO) can reduce fetal placental vascular resistance, suggest that NOmay have an important role in the promotion of the low resistance offetal placental vasculature.Monash Perinatal Unit,Departments of Obstetrics and Gynaecologyand Pharmacology,

Monash University,Clayton, 3168 Victoria, Australia

N. M. GUDER. G. KINGS. P. BRENNECKE

1. Vallance P, Collier J, Moncada S. Effect of endothelium-derived nitric oxide onperipheral arteriolar tone in man. Lancet 1989; ii: 997-1000.

2. Gude NM, Rice GE, King RG, Boura ALA, Brennecke SP. Analysis of the responsesof the fetal vessels of human perfused placental lobules to acute infusions ofarachidonic acid. Reprod Fertil Dev 1990; 2: 591-96.

3. Mak, KK-W, Gude NM, Walters WAW, Boura ALA. Effects of vasoactive autacoidson the human umbilical-fetal placental vasculature. Br J Obstet Gynaecol 1984; 91:99-106.

4. Rees DD, Palmer RMJ, Moncada S. Role of endothelium-derived nitric oxide in theregulation of blood pressure. Proc Natl Acad Sci USA 1989; 86: 3375-78.

5. Vanhoutte PM. Relaxing and contracting factors: biological and clinical research.Clifton, NJ, Humana Press, 1988.

6. Martin W, Villani GM, Jothianandan D, Furchgott RF Selective blockade of

endothelium-dependent and glyceryl trinitrate-induced relaxation by hemoglobinand by methylene blue in the rabbit aorta. J Pharmacol Exp Ther 1985; 232: 708-16.

7. Vargaftig BB, Dao Hai N. Selective inhibition by mepacrine of the release of "rabbitaorta contracting substance" evoked by the administration of bradykinin.J Pharmac Pharmacol 1972; 24: 159-61.

8. Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for

aspirin-like drugs. Nature 1971, 231: 232-35.9. Higgs GA, Flower RJ, Vane JR. A new approach to anti-inflammatory drugs. Biochem

Pharmacol 1979; 28: 1959-61.10. Kawano M. Mori N. Prostacyclin producing activity of human umbilical, placental

and uterine vessels. Prostaglandins 1983; 26: 645-62.11. Krishna BR, King RG, Brennecke SP. Effect of indomethacin on materno-fetal

amino acid transfer in the dual-perfused human placental cotyledon. Reprod FertilDev 1990; 2: 597-602.

Hepatitis A virus immunisationSIR,-Dr Higgins and her colleagues in East Anglia (Nov 24,p 1330) are worried that antibodies against hepatitis A virus (HAV)will disappear from their blood donor population with time so thatthey will have to prepare gammaglobulin from the blood of selecteddonors or devise a way to produce monoclonal antibodies againstHAV. A simpler solution would be to use one of the new inactivatedhepatitis A vaccines to immunise several plasmapheresis donors.Immunisation of British travellers to hyperendemic hepatitis Aareas will also reduce the future demand for gammaglobulinprophylaxis in travellers. The new hepatitis A vaccines will

probably be on the market in most European countries within a yearor so.’ 1

Department of Infectious Diseases,University of Goteborg,41685 Goteborg, Sweden STEN IWARSON

1. Iwarson S. Specific prophylaxis against hepatitis A. In: Infectious diseases of the liver.Falk symposium 54. London: Kluwer Academic Publishers, 1990: 373-77.

Commercial immunoglobulins and HCVSIR,—Several workers have discussed the hepatitis C virus (HCV)infectivity of fractionated products of plasma and the convenienceof exclusion of anti-HCV-positive plasma from fractionation

pools.1-4 The presence of anti-HCV in plasma from fractionationpools differs according to the origin of donor. We have investigatedsixteen lots of intramuscular immunoglobulins (Ig) from sevendifferent manufacturers in Spain.Anti-HCV was detected with the Ortho HCV antibody ELISA

test system (Ortho Diagnostic Systems, Raritan, New Jersey,USA). Igs were tested undiluted and at dilutions between 1 in 20and 1 in 1000. All Igs were also tested by the Chiron-Orthorecombinant immunoblot assay (RIBA). All samples tested positive

with ELISA, even at maximum dilution (1 in 1000). All Igs reactedstrongly with both the 5-1-1 and the C-100 antigen with RIBA.

Intramuscular Ig prevents post-transfusion non-A, non-Bhepatitis6,7 and hepatitis C infection in at-risk sexual partners.8 Ifthere were no risk of Ig containing virus, the presence of largequantities of anti-HCV make Ig highly appropriate in the

prevention of HCV transmission. We tested twenty hospitalworkers (aged 16-53, mean 34-8) who had been injected with500 mg of one of the intramuscular Igs (’Beriglobina’, InstitutoBehring). They had been injected 8-20 (mean 15-5) months before,as part of a preventive programme in case of accidental exposure.No subjects showed any symptoms during that period; serumalanine aminotransferase concentrations were normal and all

subjects tested HCV-negative by Ortho ELISA.Although our data are few, they support the traditional belief in

the safety of Ig. In the absence of a vaccine, Ig is the only specificprophylaxis available. We therefore conclude that instead of theexclusion of all anti-HCV positive plasma from fractionation pools,more effort should be made to promote safer viricidal treatments for

laboratory workers.

Microbiology Serviceand Infectious Epidemiology Unit,

Hospital NS Aranzazu,20080 San Sebastián, Spain

EMILIO PÉREZ-TRALLERO

GUSTAVO CILLAMIRIAN ITURRIZAMILAGROSA MONTES

JOSE R. SAENZ

1. Habibi B, Garretta M. Screening for hepatitis C virus antibody in plasma forfractionation. Lancet 1990, 335: 855-56.

2. Finlayson JS, Tankersley DL. Anti-HCV screening and plasma fractionation; the caseagainst. Lancet 1990; 335: 1274-75

3 Thomas PD. Immunoglobulins and hepatitis C virus Lancet 1990; 335: 1531.4 Cash JD. Screening donors for hepatitis C virus antibody. Lancet 1990; 336: 309.5. Minor P, Pipkin P, Thorpe R, Thomas D. Antibody to hepatitis C virus in plasma

pools. Lancet 1990; 336: 1886. Conrad ME Prevention of post-transfusion hepatitis. Lancet 1988; ii: 217.7. Sanchez-Quijano A, Lissen E, Diaz-Torres MA, et al. Prevention of post-transfusion

non-A, non-B hepatitis by non-specific immunoglobulin in heart surgery patients.Lancet 1988; i: 1245-49.

8. Piazza M. Periodic gammaglobulin to prevent hepatitis C in at-risk sexual partners.Lancet 1990; 336: 823-24.

Specificity of anti-HCV ELISA assessedby reactivity to three immunodominant

HCV regionsSIR,—The specificity of the hepatitis C antibody ELISA has beenquestioned, and false reactivity has been attributed to antibodies tosuperoxide dismutase (SOD),1 to rheumatoid factory and to

hyperglobulinaemia, often in association with autoimmune chronicactive hepatitis.3,4 ELISA specificity has been compared withfindings in a recombinant immunoblot assay (RIBA) whichcontains three bands-the recombinant HCV protein C-100, whichis produced in yeast as a fusion protein with SOD; the 5-1-1fragment of C-100, an SOD fusion protein produced in Escherichiacoli; and recombinant SOD (control). In some high-riskpopulations (eg, patients with haemophilia), 92% of ELISA-reactive sera were also reactive with the C-100 and 5-1-1 RIBAbands.5 For low-risk populations, such as US blood donors, only 14of 75 (19%) ELISA repeat reactive samples were positive by RIBAand 15 (20%) were indeterminate.6 Similar results were obtainedfor European blood donors.’We report here the results of an alternative method to evaluate the

specificity of the ELISA. In the semi-automated dot-blot assay(’Matrix’ HCV; Abbott) purified recombinant antigensrepresenting three immunodominant regions of the HCV genomeare spotted on discrete locations in a nitrocellulose reaction cell.8The test panel consisted of yeast-derived SOD-C-100 plus threerecombinant polypeptides expressed in E coli as fusions withCMP-KDO synthetase (CKS).9 The peptides are derived fromC-100, core (putative capsid), and 33c (figure). Diluted specimensare transferred to the test cells and incubated for 1 h at 35°C,followed by sequential 30 min incubations with biotinylated goatanti-human IgG, rabbit anti-biotin conjugated to alkaline

phosphatase, and bromochloroindolyphosphate. All steps exceptthe addition of the specimen and reagents are automated. The