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AN ERROR TRACKED TO ITS SOURCE
1268 in the aperture. Again, organisms may be introduced by non-sterile enema syringe used to blow air into the blood bottle to speed transfusion with positive pressure. The organisms introduced will probably not cause a reaction, but they are likely to increase in the remnant of donor blood. In many severe reactions the remnants of donor bloods prove sterile on culture. Proof that an organism caused a transfusion reaction depends on recovering it from the remnant of donor blood and from the recipient’s blood. I have never known this happen, for clinicians seldom culture the recipient’s blood when febrile reactions occur. Also, in doing necropsies when death is thought to be due to transfusion, pathologists sometimes omit to take samples of blood for culture. In the two cases reported by Dr. McEntegart in which death is attributed to gram-negative bacilli recovered from remnants of donor bloods, blood for culture was not taken from the recipients either ante or post mortem. The verdict in these cases must be " not proven." Bottles of culture-media ought to be available in all blood-banks so that, should febrile reactions complicate transfusion, the clinician may immediately culture the recipient’s blood. The time to do this is during the reaction, not some hours later. a
The
source of the organisms in Dr. McEntegart’s two may, apparently, have been the plastic-cap preDr. McEntegart suggests that these servative fluid. which multiply at low temperature, may have organisms, entered the bottles through the tracks in the rubber wads left by the blood-taking needles, such entry being facilitated by contraction of the cap and cooling of the blood. This may be so, though the explanation is possibly slightly different. When the blood-taking needle is withdrawn a film of blood may be left in its track through the wad. From a film of fluid under the cap, organisms could grow along the film of blood left in the track of the blood-taking needle and so enter the bottle. Accordingly, the use of sterilised caps does not seem to be the answer, since a film of either blood or cap-preservative fluid might be left between cap and wad. This film could become contaminated either by airborne organisms which settled on the bottle cap during phlebotomy, or by organisms from the fingers of those who handled the bottle. For this reason the persistence of a film of fluid or blood on the surface of the rubber diaphragm, particularly over the perforation left by the blood-taking needle, is undesirable and, therefore, it seems best not to use plastic bottle-caps. The omission of such a cap will ensure that no film of fluid or blood will persist on the surface of the rubber wad. After blood collection the surface of cap and wad should be wiped dry with sterilised lint or towel. Plastic caps are, in any event, not always effective seals, for it is sometimes possible to remove the metal cap with plastic cap intact and replace it so. This being so, it may be impossible to tell whether or not a bottle has been opened. It is to be hoped that studies will be made to ascertain whether the organisms described by Dr. McEntegart produce endotoxin or exotoxins and, if so, their nature and antidote, if any. Apparently, the noxious effects of such organisms are produced by their toxins and not by their proliferation after introduction into the body. Experimental evidence hereon might be useful. R. J. DRUMMOND cases
Welsh
Regional Blood Transfusion Service, Rhyd Lafar, near
Medical Director.
Cardiff.
AN ERROR TRACKED TO ITS SOURCE
SIR,-In a letter which appeared in your issue of Nov. 26, 1955, Sir Selwyn Selwyn-Clarke questioned my accuracy (in an article published two weeks earlier) in ascribing to Galen the phrase " Employment is Nature’s best physician, and is essential to human happiness," but did so in the politest possible terms, saying : "Would the authors add to my debt to them actual source where this wise saying can by giving the be found ? " He has had a long time to wait for his answer, but it may gratify him to know that his doubts have given
extensive search of both secondary and original my part, and that several colleagues more learned than I (including Dr. lago Galdston, of the New York Academy of Medicine, Prof. John Fulton, of Yale, and the eminent Greek scholar, Gilbert Highet) have joined in the quest. I am obliged to Dr. K. Rawnsley of this unit for having found the answer to this problem, on p. 81 of Occupational Therapy Source Book, edited by Sidney Licht (Williams & Wilkins, Baltimore, 1948). In his foreword, to a paper first published in Boston in 1914 by Dr. Eva C. Reid, an ardent advocate of ergotherapy, Dr. Licht points out that here for the first time appears " that famous quotation attributed to Galen which has since found its way, in one form or another, into dozens of pamphlets, papers and books." Galen did not say " Employment is nature’s best physician," but he did (in the first book of De Sanitate Tuendae) write" Exercise is Nature’s physician," in a passage which was cited in Burton’s The Anatomy of Melancholy. An imperfect recollection of this passage, coloured by her own zeal for work therapy, led Dr. Reid to coin a memorable
rise to
an
sources
on
misquotation. It is a pity that Galen phrase is too eloquent to
was
not its
author; but the
be
rejected. I shall continue to use it in lectures on occupational psychiatry, but, thanks to Sir Selwyn Selwyn-Clarke’s vigilance and my colleague’s detective work, I shall in future ascribe it to its proper author, Dr. Eva Reid. Social Psychiatry Research Unit, Institute of Psychiatry,
Maudsley Hospital, London, S.E.5.
P.S.-If Sir
time, I shall
G. M. CARSTAIRS. Selwyn-Clarke knew this all the
Selwyn forgive
never
him.
PREGNANCY IN ACUTE LEUKÆMIA TREATED WITH 6-MERCAPTOPURINE
SIR,,-The association of leukaemia and pregnancy is not very uncommon. In most of the examples reported the patients had chronic leukaemia. Where pregnancy has been associated with acute leukaemia, this has usually developed during the pregnancy ; it is rarer for pregnancy to start in a patient who already has acute leukaemia. Acute leukaemia is often treated with 6-mercaptopurine (6-m.P.), which is especially damaging to embryonic directed primarily against relatively undifferentiated cells. Experiments with tadpolesand rats2 have shown the danger to the foetus of using this substance. In rats 6-M.P. induced fcetal death or shunting of growth in surviving foetuses. The foetus was most sensitive at the time of implantation-i.e., the seventh or eighth day in the first seven or eight days of gestationwhen two doses of 5 mg. per kg. induced death and resorption of half the foetuses and two doses of 10 mg. per kg. induced resorption of 90%. We have treated with 6-M.P. acute lymphatic leukaemia in a young woman who, after this treatment had been started, conceived and was later delivered of a 30-week infant which lived for two days and which was apparently normal. The 6-M.P. was given before and after conception in a dosage of 2-5 mg. per kg. daily, and as far as we could ascertain produced no ill effects on the child. The patient, a white woman aged 25, was first seen on Sept. 23, 1955, after being ill for a month with weakness, malaise, tiredness, effort dyspncea, pallor, and spontaneous
tissues, being
bruising.
On examination she
was pale, with a two-fingerenlargement of the spleen, and three-fingerbreadth enlargement of the liver. She was menstruating at this time. A blood-count showed haemoglobin 4 g. per 100 ml., packed-cell volume 8%, and white cells 8400 per c.mm. (40% polymorphs and numerous primitive cells,
breadth, smooth,
non-tender
1. Bieber, S., Bieber, R., 1954, 60, 207. 2. Thiersch, J. B. Ibid,
Hitchings, G. H. p. 220.
Ann. N.Y. Acad. Sci.
The
source of the organisms in Dr. McEntegart’s two may, apparently, have been the plastic-cap preDr. McEntegart suggests that these servative fluid. which multiply at low temperature, may have organisms, entered the bottles through the tracks in the rubber wads left by the blood-taking needles, such entry being facilitated by contraction of the cap and cooling of the blood. This may be so, though the explanation is possibly slightly different. When the blood-taking needle is withdrawn a film of blood may be left in its track through the wad. From a film of fluid under the cap, organisms could grow along the film of blood left in the track of the blood-taking needle and so enter the bottle. Accordingly, the use of sterilised caps does not seem to be the answer, since a film of either blood or cap-preservative fluid might be left between cap and wad. This film could become contaminated either by airborne organisms which settled on the bottle cap during phlebotomy, or by organisms from the fingers of those who handled the bottle. For this reason the persistence of a film of fluid or blood on the surface of the rubber diaphragm, particularly over the perforation left by the blood-taking needle, is undesirable and, therefore, it seems best not to use plastic bottle-caps. The omission of such a cap will ensure that no film of fluid or blood will persist on the surface of the rubber wad. After blood collection the surface of cap and wad should be wiped dry with sterilised lint or towel. Plastic caps are, in any event, not always effective seals, for it is sometimes possible to remove the metal cap with plastic cap intact and replace it so. This being so, it may be impossible to tell whether or not a bottle has been opened. It is to be hoped that studies will be made to ascertain whether the organisms described by Dr. McEntegart produce endotoxin or exotoxins and, if so, their nature and antidote, if any. Apparently, the noxious effects of such organisms are produced by their toxins and not by their proliferation after introduction into the body. Experimental evidence hereon might be useful. R. J. DRUMMOND cases
Welsh
Regional Blood Transfusion Service, Rhyd Lafar, near
Medical Director.
Cardiff.
AN ERROR TRACKED TO ITS SOURCE
SIR,-In a letter which appeared in your issue of Nov. 26, 1955, Sir Selwyn Selwyn-Clarke questioned my accuracy (in an article published two weeks earlier) in ascribing to Galen the phrase " Employment is Nature’s best physician, and is essential to human happiness," but did so in the politest possible terms, saying : "Would the authors add to my debt to them actual source where this wise saying can by giving the be found ? " He has had a long time to wait for his answer, but it may gratify him to know that his doubts have given
extensive search of both secondary and original my part, and that several colleagues more learned than I (including Dr. lago Galdston, of the New York Academy of Medicine, Prof. John Fulton, of Yale, and the eminent Greek scholar, Gilbert Highet) have joined in the quest. I am obliged to Dr. K. Rawnsley of this unit for having found the answer to this problem, on p. 81 of Occupational Therapy Source Book, edited by Sidney Licht (Williams & Wilkins, Baltimore, 1948). In his foreword, to a paper first published in Boston in 1914 by Dr. Eva C. Reid, an ardent advocate of ergotherapy, Dr. Licht points out that here for the first time appears " that famous quotation attributed to Galen which has since found its way, in one form or another, into dozens of pamphlets, papers and books." Galen did not say " Employment is nature’s best physician," but he did (in the first book of De Sanitate Tuendae) write" Exercise is Nature’s physician," in a passage which was cited in Burton’s The Anatomy of Melancholy. An imperfect recollection of this passage, coloured by her own zeal for work therapy, led Dr. Reid to coin a memorable
rise to
an
sources
on
misquotation. It is a pity that Galen phrase is too eloquent to
was
not its
author; but the
be
rejected. I shall continue to use it in lectures on occupational psychiatry, but, thanks to Sir Selwyn Selwyn-Clarke’s vigilance and my colleague’s detective work, I shall in future ascribe it to its proper author, Dr. Eva Reid. Social Psychiatry Research Unit, Institute of Psychiatry,
Maudsley Hospital, London, S.E.5.
P.S.-If Sir
time, I shall
G. M. CARSTAIRS. Selwyn-Clarke knew this all the
Selwyn forgive
never
him.
PREGNANCY IN ACUTE LEUKÆMIA TREATED WITH 6-MERCAPTOPURINE
SIR,,-The association of leukaemia and pregnancy is not very uncommon. In most of the examples reported the patients had chronic leukaemia. Where pregnancy has been associated with acute leukaemia, this has usually developed during the pregnancy ; it is rarer for pregnancy to start in a patient who already has acute leukaemia. Acute leukaemia is often treated with 6-mercaptopurine (6-m.P.), which is especially damaging to embryonic directed primarily against relatively undifferentiated cells. Experiments with tadpolesand rats2 have shown the danger to the foetus of using this substance. In rats 6-M.P. induced fcetal death or shunting of growth in surviving foetuses. The foetus was most sensitive at the time of implantation-i.e., the seventh or eighth day in the first seven or eight days of gestationwhen two doses of 5 mg. per kg. induced death and resorption of half the foetuses and two doses of 10 mg. per kg. induced resorption of 90%. We have treated with 6-M.P. acute lymphatic leukaemia in a young woman who, after this treatment had been started, conceived and was later delivered of a 30-week infant which lived for two days and which was apparently normal. The 6-M.P. was given before and after conception in a dosage of 2-5 mg. per kg. daily, and as far as we could ascertain produced no ill effects on the child. The patient, a white woman aged 25, was first seen on Sept. 23, 1955, after being ill for a month with weakness, malaise, tiredness, effort dyspncea, pallor, and spontaneous
tissues, being
bruising.
On examination she
was pale, with a two-fingerenlargement of the spleen, and three-fingerbreadth enlargement of the liver. She was menstruating at this time. A blood-count showed haemoglobin 4 g. per 100 ml., packed-cell volume 8%, and white cells 8400 per c.mm. (40% polymorphs and numerous primitive cells,
breadth, smooth,
non-tender
1. Bieber, S., Bieber, R., 1954, 60, 207. 2. Thiersch, J. B. Ibid,
Hitchings, G. H. p. 220.
Ann. N.Y. Acad. Sci.