401

also set up. Cultures were labelled with 7 µCi myo-(2-3H)-inositol (specific activity 4-5 Ci per mmol.). After 30 min.,stimulants were added, and the lymphocytes were incubated fora further hour. The washed cells were freeze-thawed four

times, and 4 ml. of 10% trichloroacetic acid (T.C.A.) was added.The precipitate was washed once more with 5% T.C.A., and thesedimented residue was solubilised in 1 ml. NCS solubiliser andmixed with scintillating fluid. Incorporation of myo-(2-3H)-inositol into phosphatidylinositol was expressed as counts perminute (c.p.m.) per 4 x 10" lymphocytes for the time assayed.

All fatty acids studied caused a significant inhibition ofP.H.A. and P.P.D. induced myo-(2-3H)inositol incorporationinto phosphatidylinositol of lymphocytes. Arachidonicacid gave the highest inhibitory activity with P.H.A. andP.P.D. stimulated lymphocytes. Oleic acid showed thelowest inhibitory effect with both stimulants. The inhibi-tory pattern of arachidonic acid and linoleic acid wasmore pronounced with P.H.A. than with P.P.D. stimulatedlymphocytes. p.G.E1 and p.G.E2 also appeared to inhibitthe myo-(2-3H)inositol incorporation into phosphatidyl-inositol of lymphocytes.

Studies are in progress to find out if multiple-sclerosispatients and control subjects differ in the way F.A. and

prostaglandins inhibit myo-(2-3H)inositol incorporationinto the phosphatidylinositol of lymphocytes.

Inhibition of myo-(2-3H)inositol incorporation into

phosphatidylinositol of lymphocytes by F.A., P.G.Ei, andp.G.E2 might be related to direct blocking of the membrane-associated receptor or to the changes in the permeabilityof the lymphocyte membrane.

P.G.E, and p.G.E. were kind gifts from Dr Srivastava, Instituteof Hygiene, Social and Preventive Medicine and EnvironmentalScience, Odense, Denmark.

Neurochemical Institute,Radmandsgade 58,

DK-2200 Copenhagen N,Denmark.

H. OFFNER

J. CLAUSEN.

SPLENIC LYMPHOCYTES IN CHRONIC

MYELOID LEUKÆMIA

SIR,-We should like to comment on the interestingreport by Dr Kaur and her colleagues (May 4, p. 834) onthe increase of T lymphocytes in the spleen in chronicmyeloid leukaemia (C.M.L.). They are inclined to excludethe possibility that the observed increase of T lymphocytesis a relative one, as a result of a selective destruction ofB lymphocytes. Our observations on the lymphocytecontents of C.M.L. spleen (table I) could give strong thoughindirect support to their interpretation. The lymphocytepercentage has been determined by counting at least 3000nucleated cells on fresh spleen smears. It is quite clearthat in all cases there was a reduction of the relativelymphocyte number, but an actual increase of the absolute

TABLE I-LYMPHOCYTES IN SPLEEN IN CHRONIC MYELOID LEUKAEMIA

TABLE II-KARYOTYPE OF MARROW AND SPLEEN CELLS IN CHRONIC

MYELOID LEUKaeMIA

lymphocyte number, as compared with normal spleen,whose mean weight is lower than 200 g. According to thefindings of Dr Kaur and her colleagues, this absoluteincrease should be accounted for specifically by Tlymphocytes.We have also studied simultaneously the karyotype of

marrow and spleen cells in early C.M.L., and the results(table 11) suggest that spleen myeloid cells are more oftenhypodiploid, pseudodiploid, and hyperdiploid than marrowcells. Moreover, the frequency of the metaphases carrying2 Ph’ chromosomes was higher in the spleen than inmarrow. We suggest that the spleen plays an active rolein the development of C.M.L. towards blastic crisis, eitheras a source of more malignant blast cells, or as an abnormalhxmopoietic environment which offers a selective growthadvantage to abnormal variants coming from outside theorgan. The absolute increase of C.M.L. spleen lymphocytescould be regarded as an immunological response againstthese malignant cells. However, it should not be over-looked that this reaction does not prevent the developmentof blastic crisis, and that the spleen eventually becomes apreferential site of accumulation of blast cells, whateverits lymphocyte contents, so that further investigationswould be useful in order to clarify the actual meaning ofthe observed increase of T lymphocytes, and its biologicaland clinical relevance.

Division of Hæmatology,St. Orsola University Hospital,

40138 Bologna, Italy.

MICHELE BACCARANIALFONSO ZACCARIASANTE TURA.

T LYMPHOCYTES IN INFECTIOUSMONONUCLEOSIS

SIR,-During the past three years markers for lymphoid-cell differentiation have been used in the study of lympho-proliferative disorders.1 B cells carry a high density ofimmunoglobulin on their surface 2 and can easily beidentified by immunofluorescent techniques, while T cellsare identified by their ability to form rosettes directlyunder certain experimental conditions with sheep red-blood cells.3 With these techniques we are able to detectany shift in the ratio between the two populations ofcirculating lymphocytes. To our knowledge lymphoid-cellmarkers have not yet been applied in the study of infectiousmononucleosis, and we here report one case in whichthis was done.

A medical student, aged 18, was diagnosed as having infectiousmononucleosis, confirmed by haematological and serological

1. Jondal, M., Holm, G., Wigzell, H. J. exp. Med. 1972, 136, 207.2. Wilson, J. D., Nossal, G. I. ibid. 1971, ii, 788.3. Brain, P., Gordon, J., Willets, W. A. Clin. exp. Immun. 1970, 8, 1.

402

investigation. The white-cell count was 16,000 per c.mm.(20% neutrophils, 12% lymphocytes, and 4% monocytes).The remaining white cells were classified as atypical lymphocytes.A sheep red-cell rosette test was applied on the llth day ofillness, and 80% of the lymphoid cells were positive. The normalrange for peripheral blood lymphocytes forming rosettes inthis laboratory is 40-60%.We plan to extend this work to a larger number of

patients, but it seems clear that the infective agent in thispatient provoked a T-cell reaction.

Unlike chronic lymphocytic leukaemia (characterised asB malignancy) and acute lymphoblastic leukaemia (inwhich the cells lack B and T markers), in infectious mono-nucleosis the T-cells would seem to be involved.

Department of Hæmatology,Diagnostic and Therapeutic

Institute of Piraeus,Metaxas Memorial Hospital for

Cancer,51 Botassi Street,Piraeus 30, Greece.

B. SEITANIDISK. SASARI.

UNDERGRADUATE TRAINING INOCCUPATIONAL MEDICINE

SIR,-May I comment briefly upon Dr Waldron’s

paper (Aug. 3, p. 277) ? The reason why I have " arguedforcefully " that occupational medicine should be taughtand examined as part of general medicine is that everydoctor has to (and ought to) answer the questions: Whencan a patient return to work ? Must he change his job ?Should he retire from work for medical reasons ? Thesequestions cannot be answered without relating health tojob in a systematic way-and without knowing moreabout the job than that it merely consists of heavy work,light work, or just work. A second but less importantquestion is: Did the work cause the illness ? Althoughenvironmental conditions in industry are improving, soalso is public knowledge of and sensitivity to them

increasing.The answers to these questions do not need expensive

laboratory techniques, but are to be found in the takingof a careful occupational history, which needs occasionallyto be supplemented by a telephone call or a visit to theworks.

Writing the " occupation " of the patient on the case-notes in a space about twice the size of a postage stamp isnot enough.There is a great deal of specialised epidemiology,

toxicology, and occupational hygiene which is proper to adepartment of occupational or industrial health, but its

undergraduate teaching should be integrated as closelyas possible with that in general medicine.

Nuffield Department of IndustrialHealth,

University of Newcastle upon Tyne,Newcastle upon Tyne NE2 4AA. R. C. BROWNE.

NEW CONCEPTS IN MEDICAL EDUCATION

SiR,-During the past two decades no aspect of medicaleducation has been spared the careful scrutiny of expertsof one sort or another. These endeavours have produced,among other things, a class of

" professionals in educa-tional science "1 who now occupy positions in depart-ments of medical education or in centres for the develop-ment of medical education in many different countries.Their role for progress in medical education is no longerdoubted and their influence both in a national contextand internationally is considerable because of the world-wide demand for trained health personnel.

1. Miller, G. E. Wld Hlth Org. publ. Hlth Pap. no. 47, 1972, p. 108.

For this reason, it is most important that whatever issuggested in student selection, curricular reform, teacherevaluation, examination system, or as an aid to learning becritically examined not only by these " professionals" "themselves but also by independent and unbiased persons.The need is urgent because while the quality of the newideas is variable (this is understandable), some of the worstof them seem to be gaining in currency. The fact that theinstitution (often one in the U.S.A.) that made the innova-tion has actually given it up after a few years is not so wellpublicised, and the result is that the exercise may becontinued in other universities, particularly in the develop-’

‘

ing countries, with no benefits at all.The World Health Organisation has a special interest

in the development of health manpower. It is, therefore,all the more surprising to learn that the competence of apractising doctor is halved every five years and that this" estimated half life of medical knowledge ... is slowlybut constantly shrinking 11.2 It would certainly be instruc-tive to know the criteria that led to these conclusions.As the history of medical education is longer than the past

two decades and goes back to classical antiquity,3 it behovesevery professional in medical education to study his subjectbackwards in time, before attempting to add to the pile ofideas of questionable value.

173 Theydon Grove,Epping, Essex. FRANCIS MARRIOTT.

SYNTHESIS OF HIGH-MOLECULAR-WEIGHT

ANTIHÆMOPHILIC FACTOR INVON WILLEBRAND’S DISEASE

SiR,—Your correspondents have explored the questionof whether the biological activities of the factor-vmcomplex are located on a single, large molecule or onseveral molecules that are closely associated in plasma.Under conditions of high ionic strength, the factor-vmcomplex can be dissociated into a high-molecular-weight(H.M.W.) subunit, containing the von Willebrand factorVIII.w.F. and factor-VIII antigen (VIIIA.G.N.), and a

lower molecular weight (L.M.W.) subunit containingantihaemophilic factor procoagulant activity (VII4. H.F,).4,5Bloom et al.11 suggested that the von Willebrand factorboth stimulates the synthesis of vin. H.F. and also servesas its carrier in plasma. In support of this hypothesis, theyhave reported the presence of L.M.W. VIIIA.H.F. in the

plasma of patients with von Willebrand’s disease followingtransfusion with cryoprecipitate, at a time when there isrelatively more vIIIA, H,F. procoagulant activity thanVIIIA.G.N.-6 We have obtained somewhat different resultsin a transfused patient with severe von Willebrand’sdisease. The pre-transfusion levels of VIlIA.H.F. andVIlIA.G. N. (the latter measured by Dr Leon Hoyer) were3 and < 0’3 units per 100 ml. respectively and there was nodetectable vniy.w.F. assayed by ristocetin-aggregation ofwashed normal platelets.7 Following transfusion with12 units of cryoprecipitate, her vIIIA. H.F. level progressivelyincreased and was 70 units per 100 ml. after 24 hours. Bycontrast, her VIIIA.G.N. and vniy.w.r. levels, after initialincreases to 38 and 40 units per 100 ml., steadily declinedto 11 and 13 units per 100 ml. after 24 hours. These

post-transfusion values are comparable to the results

2. F&uuml;l&ouml;p, T. 5th Meeting of Directors or Representatives of Schoolsof Public Health, W.H.O., Brazzaville, March, 1973.

3. The History of Medical Education (edited by C. D. O’Malley).UCLA Forum in Medical Science no. 12. Los Angeles, 1970.

4. Weiss, H. J., Hoyer, L. W. Science, 1973, 182, 1149.5. Rick, M. E., Hoyer, L. W. Blood, 1973, 42, 737.6. Bloom, A. L., Peake, I. R., Giddings, J. C. Thromb. Res. 1973,

3, 389.7. Weiss, H. J., Hoyer, L. W., Rickles, F. R., Varma, A., Rogers, J.

J. clin. Invest. 1973, 52, 2708.