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EFFECTS OF IRON AND/OR FOLATE DEFICIENCY IN RATS

* Mean plus range.

Eighteen-day-old C D male albino rats obtained from theCharles River Breeding Laboratories, North Wilmington,Massachusetts, were fed and watered ad libitum, housed inindividual screened-bottom cages, and killed after two weeks.There were fifteen rats per dietary group. The control purifieddiet contained all of the known essential nutrients and 2 mg.of iron and 1 mg. of folate per kg. of diet.The enzyme, glutamate formimino transferase, was isolated 5

from the combined livers of rats fed a control, iron-deficient,folic-acid deficient, or iron-deficient and folate-deficient diet.Its activity was assayed according to the method of Tabor andWyngarden.5The values for haemoglobin, packed-cell volume, serum-

folate, and serum-iron are shown in the accompanying table.Formimino-transferase activity (see figure) was notably and

equally diminished in the livers from iron and doubly deficient(folate and iron) rats. While it is not possible to produce anyill-effect in standard rats by omitting.folate from the diet, suchanimals nevertheless have greater urinary excretion of FIGLUand lower levels of urinary folate than rats fed folate-containingdiets.2 Formimino-transferase activity would not be expectedto be low in the livers of folate-deficient rats since the assaysystem requires the addition of T.H.F.

Thus, urinary FIGLU excretion is elevated (a) when lowfolate diets are fed and T.H.F., the accepter for the formimino

group of FIGLU, is present in low concentration, and/or (b), indietary iron deficiency, where tissue T.H.F. is presumablypresent in normal amounts but where the activity of theglutamate-formimino-transferase enzyme activity is significantlydecreased.The present results indicate that the enzyme(s) involved in

the transfer of the formimino group of FiGLU—and thus in themetabolism of one carbon unit-is(are) presumably iron-

dependent. Thus, these results support the view, expressed byChanarin et al., Vitale et al., and Velez et al., that iron deficiencymay result in a defect in folate metabolism.

J. J. VITALEDepartment of Nutrition

R. R. STREIFFDepartment of MedicineE. E. HELLERSTEINDepartment of Pathology.

Harvard School of Public Health,Harvard Medical School and

Thorndike Memorial Laboratory,Boston City Hospital,

Boston, Mass.

THE NOTTINGHAM MEDICAL SCHOOL

SIR,-I was disappointed that Sir George Pickering chose tojoin the mob shouting " a la lanteme " with anatomy ratherthan answer my question: What did his committee aim toproduce to run the Health Service ? Clinicians who act asadvisers on the training of those responsible for the HealthService have the disadvantage that disease is their livelihood.They worship at the shrine of disease and their votive offeringsare drues.

5. Tabor, H., Wyngarden, L. J. clin. Invest. 1958, 37, 824.

What our Health Service needs is a new philosophy, and areorientation towards prevention of disease and the mainten-ance of health. For this, those who work the service must havea target-normal structure and function. This brings me backagain to the word that a handful of misguided clinicians arestriving to erase from the medical curriculum-anatomy.

G. M. WYBURN.Anatomy Department,

The University,Glasgow, W.2.

A CASE FOR DIAGNOSIS

SIR,-I support your suggestion last week that universitiesare best placed to carry out research into the services requiredof general practitioners, though, of course, many of the staffengaged in such projects must be in active practice. I believe,however, that the Institute of General Practice proposed byProf. J. N. Morris and Dr. John Fry will lose much of itseffectiveness unless it takes as its title the Institute of Domi-ciliary Medical Care, and thus enlarges its field to its properdimensions.

London, W.8. DONALD C. BOWIE.DONALD C. BOWIE.

ABDOMINAL WOUND DISRUPTION

SIR,-Mr. Graham-Stewart (July 24) believes that thesolution to the problem of wound disruption lies in thesurgeon’s technique, in that he fails to suture the abdominalwall securely. Wound disruption is not limited to wounds sewnup by surgical registrars but is equally common in woundssutured securely by surgeons of international repute both inGreat Britain and in the United States.2

I do not believe that the surgical technique of wound closurein this series was faulty, but rather that the methods availableare inadequate. Every abdominal wound is potentially liableto disruption; therefore the

"

necessary steps to ensure that theabdomen is closed in such a manner that the burst abdomenbecomes a surgical rarity " should be carried out in every case.What these " necessary steps " are Mr. Graham-Stewart un-fortunately fails to tell us.

GERSHON EFRON.

Albert Einstein College of Medicine,Lincoln Hospital,Bronx, N.Y. 10454.

Public Health

Poliomyelitis in BlackburnAt the beginning of this week 19 cases of poliomyelitis, 1 of

them fatal, had been confirmed in Blackburn, Lancashire. Afurther 8 suspected cases, none with paralysis, were underobservation in Blackburn, and 4 girls from the district on

holiday in Wales were being kept in hospital at Caernarvon.Several public functions had been postponed, and people wereadvised to avoid cinemas and dance halls. Most people hadbeen immunised, and those who had not were being offeredoral vaccine.

Statistical Review for 1963

Part 11 (population tables) of the Registrar General’s Statisti-cal Review of England and Wales for 1963 has now beenpublished.4 For the fifth year in succession marriages increased;in 1963 there were 351,000. There were 854,000 live births(2°.o more than in 1962), and the ratio of boys to girls was1055. 6-9% of the live births were illegitimate.

Drug Addiction in 1964246 new drug addicts were registered in 1964, and the total

number of registered addicts increased by 19%-from 635in 1963 to 753 in 1964.s Since the total number of addicts isunknown it is not clear whether these figures represent a

1. Efron, G. Lancet, 1965, i, 1287.2. Mayo, C. W., Lee, M. J. Archs Surg. 1956, 62, 883.3. See Guardian, Aug. 16 and 17, 1965.4. Statistical Review of England and Wales for the Year 1963. Part II:

Tables, Population. H.M. Stationery Office, 1965. Pp. 173. 18s.5. Working of the International Treaties on Narcotic Drugs. Report to

the United Nations by Her Majesty’s Government in the UnitedKingdom of Great Britain and Northern Ireland. Home Office, 1965.

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national increase of this order, or whether improvements inthe means of observing and registering addicts have played apart. Nearly 50% of registered drug addicts became addictedas a result of therapy. The commonest drugs of addictionwere heroin, morphine, pethidine, and cocaine.

Flavouring Agents in FoodThe Food Standards Committee has advised the Govern-

ment to prohibit the use of the following flavouring agents infood:

CoumarinTonka beanSafroleSassafras oil

Dihydrosafroleiso-Safrole

Agaric acidNitrobenzeneDulcamara

Pennyroyal oilOil of tansyRue oil

Birch tar oilCade oilVolatile bitteralmond oil

Male fern

Meat InspectionRegulations made in 1963 gave local authorities two years,

ending on Oct. 1, 1965, in which to arrange for all meat atslaughterhouses to be inspected. This period is now extendedby one year.

ObituaryEDMUND OLIVER LEWIS

C.B.E., M.A. Cantab., B.Sc. Wales, D.Sc. Lond., M.R.C.S.

Dr. E. O. Lewis, a former Lord Chancellor’s Visitor,died in London on Aug. 8.

Dr. Lewis graduated B.sc. from University College, Aberyst-wyth, in 1903. He obtained his Cambridge M.A. in 1908, andafter further postgraduate study at Jena he took his D.sc. Lond.in 1910. He held an appointment as demonstrator in experi-mental psychology at Cambridge, and in educational psychologyunder the London County Council, before taking his M.R.C.S.from University College Hospital in 1921. As a medical inspec-tor of the Board of Control he organised a survey of mentaldeficiency, over a period of two and a half years in six areas,which established an average of 8-57 defective people per 1000population-a proportion far higher than that previouslyaccepted. He became a commissioner of the Board in 1931, andin this capacity he produced a report on the relief of the casualpoor which led to reforms in the administration of casual wards.He was appointed a Lord Chancellor’s Visitor in 1944. He wasa member of the neuroses commission of the Medical ResearchCouncil, and served as president of the psychiatric section ofthe Royal Society of Medicine.

L. S. P. writes:" I had the privilege of becoming acquainted with E. 0.

Lewis not long after he had completed, in 1929, his massivesurvey of the incidence of mental deficiency in England andWales. His results were of exceptional value for understandingthe magnitude of administrative problems. They also led to anew appreciation of the scientific groundwork of the subjectbecause the medical and sociological elements in the concept ofmental deficiency were clearly differentiated for the first time.Lewis also took great interest in other people’s researches inthis field. He was always ready to help a novice like myself byputting at my disposal, in the most modest and charming way,his great knowledge and experience.

" By his training, E. 0. Lewis was first a psychologist andlater a psychiatrist so that he was very well equipped for thedifficult official tasks which he undertook. He had a tremendouscapacity for work and he was never satisfied with secondhandreports; he would overcome every obstacle in order to make hisown direct observations on each case with which he wasconcerned. His opinions were always carefully thought out andwere very reliable. Quiet but direct in his manner, he hatedcruelty, injustice and all kinds of sham. No one could wish fora more kind and loyal friend."

Dr. Lewis leaves a widow.

LUCY MARGARET BELL NELSONM.B. Lond., M.R.C.P.

Dr. Lucy Nelson, consultant chest physician to theSouth and Central Liverpool chest clinics and to AintreeHospital, Liverpool, died on July 24 as a result of a caraccident.

Lucy Nelson was born on Nov. 22, 19 if, the daughter ofCharles Nelson who was a brilliant classics scholar. As a

student at the Royal Free Hospital she was a prize-winner, andshe graduated M.B. in 1936. After holding resident appoint-ments at the Royal Free Hospital and Watford Peace MemorialHospital, she spent a year in India on the staff of the CanadaHospital, Nasik, returning to this country to work during thewar years with the London Blood Transfusion Service and laterat Dagenham Sanatorium. She passed the M.R.c.p. examinationin 1946, and her missionary spirit again took her to India whereshe worked at the Women’s Christian Medical College,Ludhiana, Punjab, as senior physician specialising in diseasesof the chest. III health forced her to return to England, whereshe pursued her specialty at Aintree Hospital, later beingappointed to the South and Central chest clinics and ultimatelybeing promoted consultant chest physician.

F. J. W. writes:" By nature self-effacing, Lucy Nelson was yet to be found

in the forefront of clinical discussions. She had inherited herfather’s sharpness of intellect and clarity of expression, and sheapplied to clinical medicine a wealth of experience and aknowledge acquired through painstaking study and hard work.Besides her father’s gifts, she had her mother’s love of homelyand simple things. Her colleagues recognised in Lucy Nelsona remarkable physician-indeed, a remarkable woman. Theyrealised that her scientific skill was based on deep Christianfaith and compassion. The lives of many people both in thiscountry and abroad-doctors, nurses, patients, friends-havebeen enriched by her company."

GREGORY SHWARTZMANM.D. Odessa

Dr. Gregory Shwartzman, discoverer of the Shwartz-man phenomenon, died on July 21 in Philadelphia.He was born in Russia in 1896, and studied medicine

first in Odessa and then in Brussels. After leaving Russiahe worked for a time at the Lister Institute in London but

eventually made his home in the United States. There hejoined the staff of the Mount Sinai Hospital, New York,where he eventually became head of the department ofbacteriology.The reaction which now bears his name was first observed

in 1927. It consists of an area of local necrosis of the skin atthe site of injection of certain bacterial filtrates when a similarfiltrate is injected intravenously about twenty-four hours later.This is known as the local Shwartzman reaction. If bothinjections, similarly timed, are given intravenously a systemicform of the reaction results in which bilateral cortical necrosisof the kidneys is the most conspicuous feature.

Despite a tremendous amount of effort in many laboratoriesto elucidate the mechanism of these reactions, many of thebasic features are still obscure. Shwartzman’s own contributionis well summarised in his book The Phenomenon of Local TissueReactivity published in 1937 with a foreword by Jules Bordet.It is surprising that almost forty years after its discovery it isstill not clear whether the reaction is a manifestation of immune

reactivity or not. There can, however, be little doubt that insome forms of disease, both in man and in animals, the reactionplays a significant part.

Dr. Shwartzman is survived by a daughter, who is abiochemist at the University of Pennsylvania. One of histwo elder brothers was for many years senior radiologistat the London Jewish Hospital.