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Too Much Vitamin ANEARLY 25 years ago Japanese workers 1 noticed

that the crude concentrates of vitamin A then obtain-able were toxic when given experimentally in massivedoses to animals. Later work, summarised byMooRE and WANG,2 led to the recognition of skeletalfractures with intramuscular haemorrhages as thecharacteristic lesions of an excessive intake ofvitamin A in young rapidly growing rats, while olderanimals were often found to die suddenly from massivebaemorrhages in the viscera, without skeletal lesions.VEDDER and ROSENBERC 3 suggested that the lesionsin rats resembled scurvy, while LIGHT and others 4

demonstrated that the syndrome involved a hypo-prothrombinaemia, which could be corrected, withoutaffecting the bone injuries,5 by the administration ofvitamin K.The clinical observation of hypervitaminosis A,

however, pre-dated its scientific discovery by severalhundred years. Arctic explorers, at least sinceElizabethan times, have recognised that the liver ofthe polar bear is poisonous, causing drowsiness,headache, vomiting, and peeling of the skin. The

possibility that vitamin A might be the toxic agentwas raised when RoDAHL and MOORE s found thatthe liver usually contains about 20,000 I.U. per g.,which means that the fresh tissues have nearly halfthe activity of good halibut-liver oil. The symptomsreported in explorers have not included the skeletalfractures or fatal haemorrhages characteristic of experi-mental hypervitaminosis A, but their absence shouldnot rule out vitamin A as the toxic factor in bear

liver ; the explorers presumably suffered from theacute effects of one large meal of liver, whereas therats were given massive doses of vitamin A over longperiods. RODAHL has recently examined further

specimens of liver from bears killed in north-eastGreenland, and has found that the toxicity is asso-ciated with the vitamin-A fraction and not with theresidual tissues after the extraction of the vitamin.The toxic fraction, moreover, becomes innocuouswhen its vitamin A is destroyed. He has also

reported that the liver of an arctic fox, which theEskimos believe to be poisonous, came close to bear’sliver with 12,000 i.u. of vitamin A per g. ; the ediblelivers of the snow hare and walrus contained much,smaller amounts. In further investigations withvitamin A from other sources he has obtained moreevidence of the resemblance between -hypervita-minosis A and scurvy.8 s Thus both the clinical

picture and the post-mortem findings in guineapigsgiven excess of vitamin A were very similar to thosecaused by a scorbutic diet, while in each conditionthe ascorbic-acid contents of the liver and blood-serum were much reduced. In a dog large doses ofvitamin A for 57 days caused bleeding and swellingof the gums, with a reduction of the ascorbic-acidcontent of the blood from the original 0-7 mg. per100 ml. to zero.

1. Takahashi, K., Nakamiya, Z., Kawakimi, K., Kitasato, T.Sci. Pap. Inst. phys. chem. Res., Tokyo, 1925, 3, 81.

2. Moore, T., Wang, Y. L. Biochem. J. 1945, 39, 222.3. Vedder, E. B., Rosenberg, C. J. Nutrit. 1938, 16, 57.4. Light, R. F., Alscher, R. P., Frey, C. N. Science, 1944, 100, 225.5. Walker, S. E., Eylenburg, E., Moore, T. Biochem. J. 1947,

41, 575.6. Rodahl, K., Moore, T. Ibid, 1943, 37, 166.7. Rodahl, K. Nature, Lond. 1949, 164, 530.8. Ibid, p. 531.

Since there can now be no doubt that in greatexcess vitamin A is toxic, the possibility of injury byintensive therapy has to be considered. In the rattoxic symptoms only arise when the daily dose is atleast 1000 times the requirement for optimum growth ;one would expect, therefore, that man would alsotolerate doses greatly in excess of his physiologicalrequirements. In agreement with this view clinicalexperience has shown that very large doses of thevitamin-up to at least 100,000 i.-u. daily in adults,or 40 times the accepted requirement-may be takenwithout any obvious ill effects. But absurdly high over-dosing in young children has caused toxic symptoms.Thus ToonzEy and MORISSETTE 9 observed failure of

growth and skeletal abnormalities in a two-year-oldchild whose misguided mother had administered noless than 500,000 i.u. of vitamin A daily for threemonths, while DICKEY and BRADLEY 10 reportedsimilar symptoms in a three-year-old child who hadreceived 400,000 i.u. daily for at least 18 months.It is significant that in the first of these cases themother’s enthusiasm for vitamin-A therapy was onlydiscovered in the course of treatment, after a

preliminary -diagnosis of scurvy had been made.

Western Union and HealthA BASIC idea behind Western Union is " converging

progress." Article 2 of the Treaty of Brussels, signedin March, 1948, between the United Kingdom, France,Belgium, the Netherlands, and Luxembourg-and inforce for fifty years-states that " The High Con-tracting Parties will make every effort in common,both by direct consultation and in specialised agencies,to promote the attainment of a higher standard ofliving by their peoples and to develop on corre-

sponding lines the social and other related servicesof their countries." Pursuant to this article, thefive Powers have set up, under a Council of Ministersand a Permanent Commission, a series of expertcommittees, of which one is an expert committee onhealth. This committee has now held four meetings,at intervals of about six months, in London, Paris,Brussels, and Luxembourg, and will meet next atThe Hague in March, 1950.

Their first task was to study the subjects on whichprogress towards " converging development " couldbe made, and it at once became clear that there werewide gaps in the information mutually available onthe respective health services. To remedy this,a system of exchanges was adopted and later approvedby the Council of Ministers and the PermanentCommission. These interchanges have already begunto operate, and by the end of the year some tendoctors and administrators , will have spent abouta week in each of the countries concerned to reporton the public-health administration in their respective

fields : the personal contacts thus made have alreadyproved most valuable. Other subjects studied includea French proposal for a limited reciprocal recognitionof qualifications of doctors and other health workers,and subcommittees of experts have reported on thestandardisation of control of substances used for thetreatment of venereal disease, on methods of analysisof drinking-water and sewage effluents, and on the9. Toomoy, J. A., Morissette, R. A. Amer. J. Dis. Child. 1947,

73, 473.10. Dickey, L. B., Bradley, E. J. Stanford med. Bull. 1948, p. 345.

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standards of purity required for foodstuffs. Jointsubcommittees have been dealing with assistance

conventions, including treatment at spas, and withrehabilitation : the latter is now dealt with bya separate committee. The convention on social andmedical assistance, which will shortly be signed,provides that nationals of one of the four countrieswho are normally resident in another country andAre without sufficient resources shall benefit (withcertain exceptions) on an equality with the nationalsof the host country from the legal provisions for socialand medical assistance : it thus does not apply tovisitors. The scope and results will largely dependon the administrative agreements on its application,which have yet to be worked out.

Perhaps the question on which the greatest practicaladvance has so far been made is that of simplificationof health control at seaports and particularly airports.The principle has been adopted of treating the fivecountries as one country for this purpose, whichmeans the abolition of all health controls for aircraftand passengers making flights within the five countries-save in exceptional circumstances-and institutingone health control only for aircraft and passengersarriving from outside : this sounds comparativelysimple, but has involved much detailed work. TheBritish Ministry of Health have already anticipatedthis on a limited scale in the so-called " Paris experi-ment," whereby passengers from Paris no longerhave to fill up the personal declaration of origin andhealth; so its inquiries into where the previous fourteennights have been spent will no longer be a source ofribald comment.

Finally, there is the intricate question of therelation of the ’’ get together " activities of WesternUnion to those of the Council of Europe and of theWorld Health Organisation. Clearly there are somehealth questions now being considered by WesternUnion which are susceptible of treatment on a

European or world-wide scale : but it seems that

preliminary consideration and action by the WesternUnion powers has been advantageous, and that

comparative strangers should not be. admitted tooquickly to family conferences. As in other healthmatters, political considerations may providea stimulus but should be the servants and not themasters of sound technical progress. _

Operations for Mitral StenosisIN operating on the mitral valve to relieve stenosis,

two considerations have to be borne in mind. Thefirst is that with extreme stenosis of the valve theleft ventricle is small ; at necropsy the posteriorsurface-i.e., the wall of the left ventricular inflow

tract-appears short and the coronary vessels tortuouseven though unaffected by atheroma.l The secondconsideration is that artificial mitral regurgitation ispoorly tolerated by experimental animals with normalhearts, and extensive cutting of the anterior valvecarries a high mortality-rate.2 3

Both HARKEN and his team 2 and BAILEY 3 havebased their work on these facts ; by approaching1. Kirch, E. Verh. dtsch. Ges. inn. Med. 1929, 41, 324.2. Harken, D. E., Ellis, L. B., Ware, P. F., Norman, L. R. New

Engl. J. Med. 1948, 239, 801.3. Bailey, C. P. Dis. Chest, 1949, 15, 377.

through the left auricular appendage they aim at

relieving the stenosis without causing extensive

regurgitation. HARKEN, whose various methods havealready been reviewed,4 has attempted to mobilisethe rigid cusps by dividing the commissures (valvulo-plasty) ; and he has also removed a segment of theposterior leaflet. BAILEY, on the other hand, hasconfined himself to " commissurotomy," in which heextends the cut into the normal tissue surroundingthe fibrotic area of the valve, believing that theraised auricular pressure will keep the artificial

opening patent. Of 10 patients operated on by him,7 died. Among the causes of failure were cerebralembolism on the sixth day after operation an errorin technique by cutting across the valve leaflet ; post-operative obliteration by fibrin deposits of a small,calcified mitral orifice which did not permit of adequatecutting ; postoperative intrapleural haemorrhage attri-buted to the unnecessary use of heparin and incorrectfluid administration ; and severe haemorrhage due tofriability of the auricular wall (which he has oftenencountered in mitral stenosis). To these dangersmay be added two recorded by HARKEN-namely,tachycardia and dislocation of the heart from itsnatural position. Thus the risk of operating on themitral valve is still great, even in the hands of experi-enced cardiac surgeons familiar with the precautionarymeasures. These include permanent electrocardio-

graphic control and the administration of procainedrips to combat tachycardia and myocardial irrita-bility. (This precaution is now held to be more

efficacious when the procaine is injected intramurallyin a 2% solution.5) The latest development is thatMURRAY, s of Toronto, has succeeded in animal

experiments, and in two patients with mitral stenosis,in removing one mitral leaflet and replacing it by anartificial leaflet consisting of a section of cephalic veinturned inside out and strengthened with palmaris-longus tendon.Of the indirect surgical procedures, which are

designed to relieve pulmonary symptoms due tomitral stenosis, two have already been mentioned inthese columns. 7 One of these, designed to producean artificial interauricular shunt, was inspired bythe observation that mitral stenosis associated witha natural defect of this nature (Lutembacher’s syn-drome) may run a mild course, and that serious symp-toms, such as pulmonary oedema and haemoptysis, ’,are then rare. HARKEN and his team 4 holdthat an artificial auricular septal defect is indicatedonly when the cardiac output is normal and increaseson exertion, and when stenosis and regurgitationcoexist ; otherwise the fall in left-auricle pressuremay cause insufficient blood to reach the left ventricle

through the stenosed valve. Another objection to thisprocedure is that the artificial defect may becomeobliterated and that embolism may ensue ; however,work is in progress in the U.S.A. with the purposeof ensuring that the defect is both large enough andpermanent. The second method, which is less haz-

ardous, consists in creating an extra cardiac venousshunt between the right dorsal-segmental inferiorpulmonary vein and the nearby azygos vein by non-

4. Leading article, Lancet, 1949, i, 572.5. Smithy, H. G. Dis. Chest, 1949, 15, 385.6. Murray, G. Ibid, p. 394.7. Annotation, Lancet, 1949, i, 660.