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rooted in an increased genetic variability of G.-6-P.D.metabolism. The inference is unwarranted that thisincreased variability results necessarily in higher enzymeactivities in normal female cells than in normal male cells.

ROBERT J. SCHLEGELJOSEPH A. BELLANTI.

Departments of Pediatrics,Stanford University

School of Medicine and GeorgetownUniversity School of Medicine.

NEW WAYS WITH DIGOXIN

SIR,-Your editorial of Feb. 28 (p. 455) quite correctlypoints out that it is the myocardial-digoxin concentrationwhich is of prime importance in determining the thera-peutic effect of the drug. It has yet to be shown conclusivelythat in patients on routine long-term digoxin therapy thereis in fact a relationship between plasma and myocardialdigoxin concentration. Unfortunately the paper cited 1

refers to the use of a single injection of labelled digoxingiven to patients who died within 7 days of the injection.Analysis of the tissues was then made and on the basis ofthis the statement of a relatively constant ratio of serum tomyocardial digoxin was made. This is not the correct wayto approach the problem-it is necessary to determine theconcentration of digoxin in the myocardium of patients onroutine oral therapy. This can be done by the 86Rb assaymethod, which, although a bioassay method, gives a reason-ably consistent result and is sensitive enough for the

purpose. 2 In patients in routine digoxin therapy, who areconsidered to be adequately digitalised on clinical criteria,there is a wide range of concentrations of digoxin in theatrial muscle. The average atrial digoxin concentration in16 such patients was 219 ng. per g. tissue (standard error±42). There was a wide range of concentrations from 34to 648 ng. per g. tissue, but there appeared to be no correla-tion between the atrial digoxin concentration and evidenceof clinical digitalisation.3 Plasma-digoxin levels in similarpatients on oral digoxin therapy were below 2-5 ng. per ml.It does not appear correct, therefore, to state that myocardialdigoxin concentrations bear a relatively constant ratio toserum concentrations, although there is no doubt that whenthe plasma level rises above about 4 ng. per ml. then toxicityis present.4 There is a possibility that plasma-digitoxinlevels may reflect myocardial concentrations, for patients onroutine oral digitoxin therapy have a gradually rising plasma-digitoxin concentration, and appear to be adequatelydigitalised with a plasma-digitoxin level of about 30 to 35ng. per ml., and this relatively high plasma-digitoxin level isin marked distinction to the low plasma-digoxin level seenin patients who are also adequately digitalised.5.6 Whetherplasma-digitoxin concentration reflects myocardial digitoxinlevel will depend on a simultaneous analysis of the twotissues in patients who are on chronic oral therapy.There are now apparently three adequate methods of

measuring plasma-digoxin: one based on the rubidium-bioassay method, which is easy to perform although thereare some freak results 2 ; the radioimmunoassay method,which involves the production of a specific antibody whichis not easy 7-9; or the double isotope dilution technique.10The easiest of these methods technically is the radiobioassay1. Doherty, J. E., Perkins, W. H., Flanigan, W. J. Ann. intern. Med

1967, 66, 116.2. Binnion, P. F., Hawkins, S. A., Morgan, L. M. Ir. J. med. Sci. 1969,

2, 441.3. Binnion, P. F., Morgan, L. M., Stevenson, H. M., Fletcher, E.

Br. Heart J. 1969, 31, 636.4. Grahame-Smith, D. G., Everest, M. S. Br. med. J. 1969, i, 286.5. Binnion, P. F., Morgan, L. M., Fletcher, E., Pollock, A. Ir. J. med.

Sci. 1969, 2, 451.6. Binnion, P. F., Pollock, A. M., Morgan, L. M., Fletcher, E. Un-

published.7. Butler, V. P., Chen, J. P. Proc. natn. Acad. Sci. U.S.A. 1967, 57, 71.8. Smith, T. W., Haber, E. J. clin. Invest. 1969, 48, 78a.9. Smith, T. W., Butler, V. P., Haber, E. New Engl. J. Med. 1969,

281, 1212.10. Lukas, D. S., Peterson, R. E. J. clin. Invest. 1966, 45, 782.

technique, which can be performed in any routine hospitallaboratory. It is possible that in the future methods com-bining thin-layer chromatography and fluorimetry may beof value, but at the present time, when these are used tomeasure blood-digitoxin levels, their sensitivity is not highenough."

P. F. BINNION.Department of Physiology,

Queen’s University of Belfast.

L. M. MORGANE. FLETCHER.

Cardiovascular Unit andDepartment of Biochemistry,

Belfast City Hospital,Belfast.

DIPHTHEROID ORGANISMS AND

RHEUMATOID ARTHRITIS

SIR,-In 196712 we reported in your journal some pre-liminary observations on the isolation of diphtheroidorganisms from specimens of synovial membrane andfluid from patients with rheumatoid arthritis. Few controlspecimens were available and it was therefore decided toexamine a larger series. The results were publishedrecently.13 Organisms were isolated from 21 of 78 samplesof synovial membrane (27%) and from 12 of 126 samplesof synovial fluid (10%). None were recovered from57 specimens of membrane or fluid from patients witharticular disease other than rheumatoid arthritis andReiter’s disease. In patients with rheumatoid arthritis,there was a highly significant correlation between isolationand a positive sensitised-sheep-cell test (x2= 12.06,p =0-001 [n=1]).

Clasener and Biersteker,14 also writing in your journaland using similar methods to ours, recently reportedisolations of diphtheroids from 9 (25%) of 36 sets of

clippings from rheumatoid synovial membranes, even

after very strict precautions had been taken against con-tamination of the specimen from the air or the skin.However, they still considered that the organisms weremost likely to be contaminants.

In all these investigations the technique was qualitative,sone organism or hundreds being recorded as

" positive ".In an attempt to quantitate the numbers of organismspresent, we recently examined a further 20 specimens ofsynovial membrane from patients with rheumatoid arth-ritis. This was done by culturing tenfold dilutions of themembrane suspension in a fluid medium and subculturingthe individual dilutions. (The medium was passed througha Seitz-filter before use in the hope of eliminating theoccasional organism which might have been introducedduring the preparation of the medium.) We isolateddiphtheroids in 6 (30%) of the 20 specimens. This com-

pares favourably with our original isolation-rate of 27%and with Clasener and Biersteker’s figures. The positivecultures were obtained only in the undiluted suspension,except in one case where the undiluted suspension wascontaminated with staphylococci; in this case diphtheroidswere isolated from the one-in-ten dilution.Our conclusions are as follows:

(1) The organisms were isolated from the rheumatoidsynovial membranes and fluids. This view is supportedby the biochemical and other analyses 15 of the strainswhich, although not definitive, suggest that the organismsdiffer in the main from diphtheroids normally presenton human skin.

11. Seipel, H., Hueber, E. F., Deutsch, E., Lutz. U., Wichtl, M.,Jentzsch, K. Klin. Wschr. 1968, 23, 1257.

12. Duthie, J. J. R., Stewart, S. M., Alexander, W. R. M. Dayhoff, R. E.Lancet, 1967, i, 142.

13. Stewart, S. M., Alexander, W. R. M., Duthie, J. J. R. Ann. rheum.Dis. 1969, 28, 477.

14. Clasener, H. A. L., Biersteker, P. J. Lancet, 1969, ii, 1031.15. Stewart, S. M., Pratt, K. C. Unpublished.

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(2) They may only be present in the joints in smallnumbers. On the other hand, failure to isolate bacteriafrom diluted specimens may be due to the use of sub-optimal culture media which will only support growthwhen supplemented with cellular material. Alternatively,bacteria may be present in the joints in foxms which donot grow readily on artificial media.

(3) The evidence to date is insufficient to establish thatthe organisms play an xtiological role in rheumatoidarthritis-a claim which has not been made at any stagein our investigations.

SHEILA M. STEWARTW. R. M. ALEXANDERJ. J. R. DUTHIE.

University Department of Bacteriologyand Rheumatic Diseases Unit,Northern General Hospital,

Edinburgh.

APPEAL TO DOCTORS

SIR,-I agree with Sir George Thomson’s comment underthis heading (Feb. 28, p. 464), that a doctor’s value judg-ments are in no way privileged and he has no right to coercehis patients to live by his personal values or principles.Patient and doctor should each have freedom to make hisown value judgments, but each should also be free to followhis own conscience whatever may be permitted by the law.But I should like to question Sir George’s use of the

National Opinion Poll as evidence that doctors have to" find means sub rosa of getting over. difficulties

" as they

care for their dying patients. The Poll affirmed that 76-2%of 1000 doctors agreed that " some medical men do in facthelp their patients over the last hurdle in order to save themunnecessary suffering even if that involves some curtailmentof life."The term " euthanasia " by derivation can simply mean

easing death; in this sense I imagine that virtually all doc-tors would affirm that they try to help their patients over thelast hurdle. But, in the setting of the recent Euthanasia Billand the present controversy, euthanasia may be defined asthe legalised killing by a doctor of a person suffering froman incurable disease, with or without major physical suffer-ing, such a person being in his right mind and having per-sonally and voluntarily requested it. Using this definitionI would still have to answer the poll in the affirmative if Ithought that 1 in 10,000 doctors had ever practised eutha-nasia. In every profession there can be some members whofrom ignorance, weakness, or even compassion will do some-thing wrong. Regrettably, doctors have been known tocommit murder, and I have little doubt that some may havepractised euthanasia. Many of the Poll examinees must havethought this " a silly question ", for it would be extra-ordinarily naive to answer it except in the affirmative. Theanswer to such a question is hardly valid evidence for SirGeorge’s conclusion about medical practice.But my reason for writing again is not only to answer this

point in Sir George’s letter, but to emphasise the importanceof defining euthanasia. In a recent meeting I attended it wassincerely suggested that switching off the artificial respiratorin a case of hopeless head-injury, where the brain wascertainly and finally dead, was an example of euthanasia.The speaker claimed that since doctors were doing this,euthanasia was already practised and accepted, and shouldtherefore be made legal! Unfortunately lay people, missingthe error in the premise, can easily be deceived into accept-ing the false conclusion.To confuse the different meanings of the term makes it easy

to spread the false idea that euthanasia, in the sense of killingpeople, is already widely practised; and this is untrue. Itwould be an immense disservice to the sick, who are often ofvery limited understanding, to spread the idea that theirdoctors, under any circumstances, would deliberately killthem. A physician friend told me recently that he had causeto reassure a frail and ill patient with insomnia that he would

prescribe some medicine to give her a good night. He wasdismayed at her anxious reply: " I will wake up, won’t I,doctor ? "

D. MACG. JACKSON.Birmingham.

ObituaryCHARLES PAUL WBLSON

C.V.O., F.R.C.S., J.P.Mr. C. P. Wilson, emeritus consultant otolaryngo-

logist to the Middlesex Hospital, died on March 12,at the age of 69.

He was born on Aus. 17, 1900, and after attending theWalling Brook School, Devon,entered the Middlesex Hos-

pital Medical School. Heobtained prizes in chemistry,and then proceeded to distin-guish himself in anatomy andembryology. He took the

Conjoint qualification in 1922and obtained the F.R.C.S. in1925. In 1930 he was appointedto the honorary staff of theMiddlesex Hospital as assistantaural surgeon. He was also

appointed to the staff of the

Queen Victoria Memorial Hos-pital, Welwyn, and the Welwyn harden City Hospital,and continued on the staff of the new Queen Elizabeth IIHospital after he had retired from the Middlesex Hospitalin 1962. In 1939 he was appointed c.v.o. He was presidentof the Section of Laryngology of the Royal Society ofMedicine in 1953-54, Hunterian professor of the RoyalCollege of Surgeons of England in 1955, and Semonlecturer of the University of London in 1961. He was afellow of the Collegium Otorhinolaryngologicum, and in1962 was appointed a justice of the peace. He was directorof the Ferens Institute of Otolaryngology from 1945 to 1962.He is survived by his wife, their two daughters, and their

son, who is a surgeon.D. R., to whom we are grateful for these biographical

details, writes:" C. P., as he was known to his colleagues and friends,

was a man whose life was devoted to otolaryngology, tothe Middlesex Hospital and Medical School, and to hisfamily. He had a brilliant and quick mind and untiringenergy. He was widely read and could converse easilywith patients in many different occupations about par-ticular facets of their work; he not only quoted extensivelyfrom the Bible, Shakespeare, and other sources, but knewthe background and context of the quotations. He had avery real interest in people and was one of the mostgenerous of men-not only with material things, but withhis own time and energies. An exceptionally busy man, healways found time to think about the careers and problemsof his juniors and to discuss their difficulties with them.He was prepared to spend countless hours in the operating-theatre instructing his registrars and house-surgeons onthe detailed techniques of operating-a field in which hewas a master craftsman himself. Although he had aninterest in the whole of otolaryngology and made valuablecontributions to otology in the early part of his career, hismajor original work was on head and neck surgery. Hedevised an operative approach to the glossopharyngealnerve through the tonsillar fossa, and his operation hasrelieved patients of the severe intractable pain of glosso-pharyngeal neuralgia without the hazard of an intracranialoperation. His technique of transpalatal approach to the