being in CD38 + cells (49%, normal 12-40). Mitogen responsiveness was normal. The patient had received BCG vaccination at age 6 months; at age 5 years tuberculin skin reaction was negative. DSCG was started when the patient was 72years old, with the object of blocking food allergy. The dose was 2 g by mouth twice a day. After 4 months of D SCG treatment his IgE fell from 43 000 to 20 000 IU/ml and IgA rose to 500 mg/dl. In the next 3 months IgD levels increased to 360 mg/dl, IgG fell to normal, but IgM did not change. Despite the fall in total IgE, RAST scores for food antigens increased, eosinophil counts were unchanged. The CD38 + T subset fell from 28 %. The tuberculin skin test became positive. The patient improved clinically, and during one year of DSCG he had just three brief episodes of high fever, and no pneumonia, severe otitis media, or deep skin infections despite the absence of prophylactic antibiotics. The candidosis improved too. 6 months after starting DSCG, he had axillary lymphadenitis, manifested as local warmth and tenderness, suggesting improved local inflammatory responses. He gained 45 kg in a year. We thank Dr Philip L. Cohen (University of North Carolina at Chapel Hill and Dr Zenro Ikezawa (Yokohama City University) for critical comments; Dr Tadatoshi Kuratsuji (National Institute for Children’s Disease) for neutrophil function assays; and Dr Rumiko Shibata (National MinamiFukuoka Chest Hospital) for the detection of antistaphylococcal IgE antibody. This study was supported by a grant from the Ministry of Health and Welfare of Japan (National Project of Immunodeficiency Research).

Department of Paediatrics, City University School of Medicine, Yokohama, 236, Japan Yokohama


1. Davis SD, Schaller J, Wedgwood R. Job’s syndrome: recurrent, "cold", abscess. Lancet 1966; i: 1013-15. 2. Donabedian H, Gallin JI. The hyperimmunoglobulin-E recurrent infection (Job’s) syndrome: a review of the NIH experience and the literature. Medicine 1983; 62: 195-208.

Serum proteins and mortality SIR,-Dr Dame and colleagues (Feb 10, p 350) report interesting results from a large prospective study on serum albumin, serum globulin, and mortality. They suggest that the relation between serum albumin and mortality that we reported from the British Regional Heart Study (Dec 16, p 1434) may disappear after adjustment for serum globulin which, in their study, showed a strong positive association with mortality from cancer and cardiovascular disease. Serum globulin was also measured in our study. The table shows the standardised relative odds for the association between serum globulin and death from cardiovascular disease, cancer, and other causes, after adjustment for age, social class, town of residence, cigarette smoking, serum cholesterol, systolic blood pressure, serum calcium, and forced expiratory volume in 1 s. There is a significant positive association between serum globulin and mortality for all three cause groups. However, after adjustment for STANDARDISED RELATIVE ODDS FOR SERUM GLOBULIN AND SERUM ALBUMIN

the above factors plus serum albumin the associations are much reduced and non-significant. In contrast, the strong negative association between serum albumin and mortality remains even after adjustment for globulin. Thus the two studies agree on there being a strong association between serum protein and mortality from cardiovascular disease and cancer in men, but not on which protein is the more important. We measured serum globulin directly in our study and not by subtraction of serum albumin from total protein, as Dame et al did. Subtraction tends to overestimate the negative correlation between globulin and albumin, for when the serum albumin is measured too high (or too low) the serum globulin will be recorded too low (or too high). The correlation between globulin and albumin was - 0 27 in our study and - 0-45 for men in the study that Dame et al report. In part this discrepancy may explain the lack of concurrence between the two studies. Department of Clinical Epidemiology and General Practice,

Royal Free Hospital School of Medicine, University of London, London NW3 2PF, UK


Pathogenesis of Crohn’s disease SIR,-As pathologists with a special interest in gastroenterology we interested in the paper by Mr Wakefield and colleagues (Nov 4, p 1057) illustrating microscopic vasculitis in Crohn’s disease. were

This is not a new observation1 and whilst vasculitis may have a role in the pathogenesis of the disease it would be a mistake to regard it as the primary event causing multifocal infarction. Infarction is an easily recognised microscopic pattern not seen in Crohn’s disease. The earliest recognisable lesions in Crohn’s disease are aphthoid ulcers.2,3 These and granulomas in the bowel wall, found in 60-70% of patients with Crohn’s disease, are not features of ischaemia; nor are transmural aggregates of lymphocytes, an almost universal feature of the disease. Furthermore it is difficult to imagine how the anal and perianal ulceration of Crohn’s disease could be explained purely by an underlying ischaemic process-nor indeed the fmding of granulomas in rectal mucosa in cases with disease apparently limited to the small bowel. Conversely, characteristic changes of ischaemia are rarely seen in the disease and classical ischaemia enteritis does not progress to Crohn’s enterocolitis. This is not to say that ischaemia plays no role, nor indeed that there is no arteritis.However, to consider the morphology as one of multifocal infarction is, in our opinion, an inaccurate description of the pathology. Department of Pathology, Northwick Park Hospital and Clinical Research Centre, Harrow, Middlesex HA1 3UJ, UK


Department of Pathology, St Marks Hospital, London


Department of Pathology, General Hospital, Birmingham


Department of Pathology, University of Wales College of Medicine,



H, Bowser RS. Granuloma, arteritis and inflammatory cell counts in Crohn’s disease. In: Pena AS, Waterman IT, Booth CC, Strober W, eds Developments in gastroenterology: recent advances in Crohn’s disease. Hague: Martinus Nijhoff, 1980: Vol I; 80-83. 2. Rutgeerts P, Geboes K, Vantraappen G, Kerremans R, Coenegrachts JL, Coremans G. Natural history of recurrent Crohn’s disease at the ileocolonic anastomosis after curative surgery. Gut 1984; 25: 665-72. 3. Brooke BM. Granulomatous disease of the intestine. Lancet 1959; ii: 745-49. 1. Thompson

Anonymous testing for HIV infection

*Adjusted for factors listed m text. The further the figure is from one the stronger the association A figure below 1 indicates a negative association

SiR,—Publication of Professor Peckham and her colleagues’ article (March 3, p 516) and your March editorial (p 575) focuses attention on anonymous testing for HIV infection. Testing on a named basis can only be done with informed consent1 and such data are unlikely to give the true prevalence of HIV infection in the population. For planning services, for improving counselling, and for limiting the spread of HIV infection


better information is needed, and this can only be obtained by testing unnamed samples without specific consent on a wide scale In England and Wales a multicentre programme of unlinked anonymous testing has now been set Up.3,4 One of the objectives is to estimate the prevalence of HIV infection in patients of district

general hospitals. We have started unlinked anonymous testing for HIV infection in sera collected in the clinical chemistry department of East Birmingham Hospital, and report here the result of one year’s testing. More than 95% of sera were from patients living in East Birmingham. After completion of the clinical chemistry tests the residues of sera from certain days (see below) were sorted by sex and age of the patient and, usually, pools of ten sera were formed and labelled Mlto M5 and Fl to F5 (M = male, F = female; 1=1-19 years, 2 = 20-29, 3 30-39, 4 40-59; and 5 60 or more years). Where fewer than 10 sera were available the pool size was noted on the vial but the pools were not designated in any other way and neither the names of the patients nor the dates of sampling were recorded. Pools of sera from one day’s work were made up every 8 days. Known HIV-antibody positive sera were excluded. The pools were collected over two periods of 6 months and then tested in two batches. The personnel doing the HIV tests were different from those who had made up the pools. We used a passive agglutination test (’Serodia’) for the first batch and an ELISA (Abbott recombinant HIV1/HIV2) for the second batch. Confirmation of positive pools was by ELISA (’Wellcozyme’) and an in-house indirect immunofluorescence test with HTLV-IIIB-infected H9 cells. The project was approved by the ethical committees of East Birmingham Hospital and the West Midlands Regional Health =


emergency units,’ where more young people present as patients, may be more representative. Only large sets of such data from different regions of the UK and on different strata of the population will yield a picture that comes close to the true prevalence of HIV infections in the general population. We thank Dr J. W. G. Smith, Prof A. M. Geddes, and Dr E. H. Boxall for discussions and support; Dr 0. N. Gill, Dr E. Miller, and Dr M. J. Carpenter for valuable conunents; P. Norton for updated local population statistics; and Dr F. A. Ala for prevalence data on HIV seropositivity in blood donors.

Regional Virus Laboratory and Clinical Chemistry Laboratory, East Birmingham Hospital, Birmingham B9 5ST, UK



1. Editorial. General Medical Council agrees guidelines on AIDS. Br Med

J 1988; 296:

1613. 2. Anonymous. Testing for HIV infection. Lancet 1988; i: 1293. 3. Gill ON, Adler MV, Day NA. Monitoring the prevalence of HIV: foundations for a programme of unlinked anonymous testing in England and Wales. Br Med J 1989; 299: 1295-98. 4. Heptonstall J, Gill ON. The legal and ethical basis for unlinked anonymous HIV

testing. Commun Dis Rep 1989; 48: 3-6. Cahoon-Young B, Chandler A, Livermore T, Gandino J, Benjamin R. Sensitivity and specificity of pooled versus individual sera in a human immunodeficiency virus antibody prevalence study. J Clin Microbiol 1989; 27: 1893-95. 6. Kelen GD, Fritz S, Qadqish B, et al. Unrecognized human immunodeficiency virus infection in emergency department patients. N Engl J Med 1988; 318: 1645-50. 7. Krasinski K, Borkowski W, Bebenroth D, Moore T. Failure of voluntary testing for human immunodeficiency virus to identify infected parturient women in a high risk population. N Engl J Med 1988; 318: 185. 8. Miller E for PHLS Working Group. Prevalence of HIV antibody in high and low risk groups in England. Br Med J 1989; 298: 422-23. 5.

Authority. 8155 sera in 884 pools were collected between December, 1988, and November, 1989. Only 1 pool (in group M5) was HIV seropositive, yielding an annual prevalence of 1 in 8155 (95% confidence interval 1 in 1464 to 1 in 33 979). The probability that this pool contained 2 positive sera is 1 in 6-7 million. Preliminary experiments had shown that dilutions of 15 positive sera in HIV negative serum of 1 in 20,1 in 50, and 1 in 100 all scored positive. Cahoon-Young et al,-’ in an HIV antibody study, tested 5000 sera as individual specimens or in pools of 10 sera, and there was complete agreement-ie, no HIV-positive serum was missed. Thus testing of pools in epidemiological studies is justified and could lead to savings of 60-80% in labour and materials.5 Comparison of the age/sex distributions of the population served by the East Birmingham Health Authority with those of patients whose sera were pooled showed that the sex distributions were indistinguishable. The 30-59 age group was a representative

sample; however, 1-19-year-olds


under-represented by


factor of 5 and 20-29-year-olds by a factor of 2-5 whereas the 60 + age group was over-represented by a factor of 2-5. Thus the 8155 subjects are not representative of the district’s population-but the sample was not biased by self-deferral or self-referral. Underrepresentation of the under-30 age group means that our estimate of 1 in 8155 could underestimate the time prevalence of HIV

seropositivity. During the period of this study of unlinked anonymised testing 34 new HIV-positive individuals were detected by named testing in the West Midlands, which has a population of 5 2 million, resulting in an annual prevalence of about 1 in 153 000. We have not been told where most of these 34 seropositive individuals live but we estimate that

than 1 is in the East Birmingham district; there, on a very small number has detected 1 additional HIV infection. The HIV seroprevalence rate for blood donors in the West Midlands was about 1 in 101 000 in 1989. Our experience that period prevalence obtained by anonymised testing will be greater than that found by named testing accords with the data of Kelen et al6 and Krasinski et al.7 Both these studies had the advantage of application of the two testing procedures to identical no more

anonymised testing

subpopulations. Our survey is

continuing and expanding, with the support of the

West Midlands Regional Health Authority. It will complement

regional data from named testing that provide risk-factor information.g Anonymous testing of sera obtained in accident-and-

and London antenatal clinic

Retrospective study of HIV, hepatitis B, HTLV-I infection at


SIR,-Since Jan 15, 1990, selected UK antenatal clinics have been

participating in prospective studies of anonymous unlinked testing of sera for antibodies to human immunodeficiency virus (HIV). Patients are being told that their blood may be tested anonymously; and posters and leaflets about the project are being displayed. Any patient who objects to her sera being tested is excluded. However, unlinked anonymous testing could produce a biased estimate of HIV seroprevalence in the population if a large number of patients refuse to be tested. With local ethical approval and with the agreement of obstetricians we did a retrospective survey on sera from all patients who had attended antenatal clinics at St Thomas’ Hospital, London, in 1988. The hospital serves an inner-city area, parts of which are socially deprived and where many people are from ethnic minorities. Before anonymised HIV testing we tested the sera on a named basis for evidence of infection by hepatitis B virus (HBV) and HTLV-I. (It is our current practice to screen antenatal patients for HBV infection selectively, concentrating on high-risk groups.) Sera from 3760 patients were tested for HBsAg (’AUSRIA 11’ kit; Abbott Laboratories); for antibodies to HTLV-I (Abbott immunoassay), positive sera being retested by passive particle agglutination (’Serodia-ATLA’; Fujirebio), and those positive by both tests, competitive and antibody capture radioimmunoassays and western blot (Public Health Laboratory Service, UK); and for antibodies to HIV 1 and 2 by sandwich enzyme immunoassay (Abbott), with a competitive enzyme immunoassay (Wellcome Laboratories) and ’Serodia-HIV’ (Fujirebio) as confirmation. 2 sera (005%) had antibodies to HIV-1 and none to HIV-2; 38 (1 %) were HBsAg positive; and 10 (0-26%)contained antibodies to HTLV-1 (a further 3 sera were equivocal). Of the 38 sera containing HBsAg, only 22 (56%) had been previously tested, and shown to be positive, in selective screening. Of the remaining 16 sera, not accompanied by a request for HBsAg testing at time of collection, 11I were from patients of African or West Indian origin. Of the 10 patients who were HTLV-I positive 6 were of West Indian and 2 were of West African origin. 59-5 % of patients attending our antenatal clinics were white, the remaining being of Caribbean (18-2%), African (11-3%), Asian

Anonymous testing for HIV infection.

858 being in CD38 + cells (49%, normal 12-40). Mitogen responsiveness was normal. The patient had received BCG vaccination at age 6 months; at age 5...
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