EVALUATION OF LABORATORY TESTING

EVALUATION OF LABORATORY TESTING

585 an anesthetic and even perform straightforward surgical procedures without close supervision. But this requires a very high degree of medical prof...

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585 an anesthetic and even perform straightforward surgical procedures without close supervision. But this requires a very high degree of medical professionalism-which Illich

decries. The odd

thing is that in Britain, no less than in Nigeria, starting to use a health team in this way. Could possibly be the result of medical professionalism ?

we are now

it

Ahmadu Bello University,

Zaria, Nigeria.

GEORGE DISCOMBE.

" WILD WHITE " VIRUSES AND SMALLPOX

SiR,-The term " wild white " poxviruses conveniently groups together four viruses, all isolated from simian tissues and all closely resembling variola virus in laboratory tests. Two of them were isolated from apparently normal cynomolgus monkeys imported into Holland. The other two were isolated from specimens taken in Zaire from a chimpanzee and from a monkey of unidentified species.1 It has not yet been determined whether these viruses

My colleagues and I have been interested in comparing variola viruses of varying degrees of virulence and have detected several minor differences between them. It is thus often possible to say that a particular strain of variola is different from another strain of variola. Two of these tests have proved useful in the present instance. One test, which will be reported in detail elsewhere, depends on the pattern of haemadsorption produced by variola infection in human diploid-cell cultures. Variola strains may be placed in one of three groups (A, B, or C) by this test. The other test depends on the relative abilities of variola strains to grow in cultures of a continuous line of cells derived from rabbit kidney (RK13) and is measured by the amount of hsmagglutinin produced. These two tests have been applied to the three viruses mentioned and to the virus strain recovered from the index case, with the following results: Virus

group

are

strains of variola or whether they are viruses similar to variola but which are distinct from it in properties for which there is at present no laboratory test. The two Zaire specimens came from an area which has been free of smallpox for some time and in which the disease has not re-emerged.l Despite this, the existence of these wild white viruses threatens to undermine the assumption that there is no animal reservoir of variola virus; this assumption clearly affects the prospects for eradication of smallpox. The complete interruption of transmission of smallpox in all countries of the world would mean the disappearance of all human foci of infection. This goal is rapidly being approached by the W.H.O.’s smallpox-eradication campaign. Such a major achievement would need to be followed by continuing surveillance, but the difficulties of this would be greatly increased if there were a known animal reservoir of variola virus, however remote. Further definition of the nature of the wild white poxviruses is needed, as well as better knowledge of their distribution and of the hosts which maintain them in nature. The most important unknown about the wild white poxviruses is their pathogenicity for man. This question was raised during the inquiry into the smallpox outbreak in London in 1973. The committee of inquiry into that incident considered Feb. 28,1973, to be the most likely date on which the index case was infected, that being twelve days before she became ill. The viruses to which she may have been exposed on that day were four in number,3 one of which was a strain of vaccinia virus. Of the other three one was a strain of variola major which had had many passages in fertile eggs; the others were two of the wild white poxviruses, which had been isolated in Holland, and which were in their 4th and 5th passage in eggs. The committee concluded4 that the index case " contracted a highly modified form of smallpox by infection with variola major, strain Harvey or wild white strain 7275 or 7255." At the time of the inquiry there was no way of distinguishing between these three viruses, and a wild white virus could not be ruled out as a cause of the outbreak. Work done in this laboratory during the past year enables strain Harvey to be distinguished from strains 7275 and 7255, and it now seems possible to exonerate the wild white poxviruses from being the cause of the 1973 outbreak of smallpox in London. Lancet, 1974, i, 295. Report of the Committee of Inquiry into the Smallpox Outbreak in London in March and April 1973; paras 241, 242. H.M. Stationery Office 1974. ibid. appendix J.

3. 4. ibid. para 243.

H.A. units in RK" cell cultures

A B B

Harvey 7275 7255 London ’73

true

1. 2.

Haemadsorprion

0 16 32 0

A

Both tests separate the two wild white pox strains from the variola strain Harvey and the virus causing the outbreak. The strain causing the outbreak is most unlikely to have been a wild white poxvirus. These results do not prove that wild white poxviruses are not variola-other variola strains could give the same result in these tests as 7275 and 7255, and the other two wild white poxviruses from Zaire give the same results as the variola strain Harvey-but at least it can be said that so far there is no evidence of any of the wild white poxviruses being associated with human disease. ’

Department of Virology, St. Mary’s Hospital Medical School, London W2.

K. R. DUMBELL.

EVALUATION OF LABORATORY TESTING

SIR,-Periods of financial stringency always lead

us to

the effectiveness of our laboratories. We are therefore indebted to Professor Holland and Professor Whitehead for their timely contribution to the evaluation of laboratory testing (Aug. 17, p. 391). They have proposed that we use in a more general way a simple mathematical procedure originally devised to define the efficiency of a screening test in terms of sensitivity and specificity.l Wilson2 pointed out that if this results from well-defined technique is used to compare reference populations of " normals " and " abnormals ", the discriminating efficiency may be greater than in a mixed population. Since many of the tests we employ are dependent on changes in physiological and metabolic systems and are rarely disease-specific, abnormal results are often recorded in a general or hospital population which are due to some cause other than the one for which we are testing. In other words, we may need to examine the specificity of a test in relation to several abnormal population groups. As a combination of tests with low efficiency may have greater power of discrimination than any single test, more complex analysis of the data may be required before the use of a single test can be adequately evaluated. Without a more widespread understanding and appreciation of discriminant function analysis, the diagnostic value of an individual test may be underestimated. There are, of course, other sources of redundant data apart from inefficient tests. Many people are aware of the

look

more

critically

at

1. Thorner, R. M., Remein, Q. R. Wld Hlth Org. Publ. Hlth 1961, no. 67. 2. Wilson, J. M. G. J. clin. Path. 1973, 26, 555.

Monogr.

586

problem of unsolicited data, generated by multichannel analysers, which may be irrelevant to the patient’s condition. Of perhaps equal importance, but less obvious, is the repetition of observations at unnecessarily short intervals. Much laboratory effort could be saved if sampling intervals were matched more closely to the rate of change in the concentration of the substance measured. Department of Clinical Chemistry, Northwick Park

Hospital,

M. G. RINSLER.

Harrow, Middlesex HA1 3UJ.

CLASSIFICATION OF NON-HODGKIN’S LYMPHOMAS announcement in The Lancet (Aug. 17, 405-408) of two more classifications of non-Hodgkin’s lymphomas encourages me to put forward my classification

SIR,-The

pp.

of these classifications:



Well-defined, high-grade,

oligosyllabic diffuse

Poorly differentiated, polysyllabic derivative

circumlocutory

with dyslexogenesis

nlcentnc 1.. Unicentric

Multicentric, cycnophilic (Gk. 1(U1(Vo!> = swan) Cleaved and convoluted

GREY-SCALE ULTRASONOGRAPHY IN THE INVESTIGATION OF OBSTRUCTIVE

JAUNDICE clinical problem is the differentiation of obstructive jaundice due to multiple intrahepatic space-occupying lesions from extrahepatic causes which usually require surgical relief. In the presence of even moderate jaundice, the only radiological procedure of possible value is transcutaneous cholangiography-a hazardous investigation which may precipitate surgery. Operation may be highly undesirable in the presence of severe and inoperable liver disease with defects of hxmostasis. Radioisotope examination is especially unreliable in the presence of obstructive jaundice, since multiple small metastases are not adequately resolved and appear as non-specific diffuse enlargement, while dilated portions of the biliary tree caused by extrahepatic obstruction produce cold areas which simulate malignant involvement. Grey-scale ultrasonography is done with a technically sophisticated ultrasound scanner and produces a resolution of a few millimetres in the liver substance.1 It has been successfully applied to cancer diagnosis and solves the problems of differentiating between intrahepatic and extrahepatic causes of jaundice. The resolution which may be obtained and its use in this particular application are shown in the accompanying figures.

SIR,-A

common

typestypesRappaport(non-Rappaport) (non-Lukes) Lukes

no claim to be comprehensive or even there may well be scope for other classifications of classifications and ultimately, one hopes, a At that classification of classifications of classifications. point we shall need a conference in the Caribbean.

This system makes

comprehensible,

so

Royal Marsden Hospital, Fulham Road, London SW3 6JJ.

H. E. M. KAY.

ORIGIN OF MALIGNANT LYMPHOMAS

Sm,—In the past few years the B various

or

T cell

origin of the

malignant lymphomas has been the subject of many

studies, especially those employing immunological methods. However, the histological data on the initial involvement of the lymphatic tissue should also be taken into consideration. As has been well established for the lymph-node, one can clearly distinguish a B-cell and a T-cell region. The B-cell region comprises the outer part of the cortex, especially the primary and secondary nodules. The T-cell region is called the paracortical area, although we prefer the old term tertiary nodule. The first site of infiltration of a particular lymphoma might give an indication of the origin of the tumour when either the B or T cell region is primarily affected. We therefore studied the early infiltration of lymph-nodes in 8 cases of hairy-cell leukaemia (leuksemic reticuloendotheliosis) and 8 cases of Sezary syndrome. In hairy-cell leukaemia we found that the infiltration was chiefly confined to the outer cortex, whereas the tertiary nodules were at least partially intact in most cases. In contrast, in Sézary syndrome the first infiltration took place in the tertiary nodules (" paracortical area "); apart from the influx of Sezary cells through the afferent lymphatics, the primary and secondary nodules were not affected at first. These findings speak in favour of the B-cell origin of hairy-cell leukaemia and the T-cell origin of Sezary syndrome. They are consistent with many experimental data

lately reported. Institute of

Pathology, University of Kiel,

Postfach 43 24, D-2300 Kiel, Germany.

Fig. 1-Schema

show the plane of section and the anatomy.

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Fig. 2-Ultrasonogram showing parasagittal the right of the midline. The liver is bounded by the anterior abdominal wall (AAW), the diaphragm above (D), and the right kidney posteriorly (K). Multiple small black tumours can be seen replacing the normal liver substance. a

1.

K. LENNERT.

to

Taylor, K. J. W., Carpenter, D. A., MaCready, V. Ultrasound, 1973, 1, 284.

R.

cm. to

J. zur.