571CARBON TETRACHLORIDE POISONING

acquired such a distaste for the smell of carbontetrachloride that they vomited under conditionswhich previously had no effect. One plant chemistsaid,

" I have now developed a conditioned reflex andthe thought of setting about a job which involveshandling the stuff is enough to make me vomit."Temporary cerebral’effects, such as light-headedness,giddiness and vertigo followed by acute headache,occurred immediately after exposure to high concen-trations. Chronic headaches were described by someworkers. A few of them had lost consciousness whileattending to leaks or spills. Alteration of the sleep

rhythm was common. Drowsiness and failure to feelrefreshed on waking were invariably present. Somepeople slept heavily whereas others, equally drowsy,had insomnia. There was also loss of mental agilitywhich " showed itself in inability to tackle more thanone problem at a time and impatience with anythingthat demanded spontaneous enthusiasm." Depres-sion, irritability and inertia were also well-markedfeatures., One enthusiastic fisherman completelylost interest in his hobby, and others found it difficultto bestir themselves to take exercise in the fresh airthough if they did both mental and gastro-intestinalsymptoms rapidly abated.

Clinical examination of the workers was essentiallynegative. Of 170 people who had been in contactwith the solvent only one case of enlarged liver and5 cases of albuminuria were found, and all 6 recoveredwithout any sign of progressive hepatic or renaldisease. In addition a few major defects were foundsuch as acute rheumatism (1 case), essential hyper-tension (2 cases), and chronic bronchitis and emphy-sema (4 cases), together with a fairly high incidence ofminor defects. It was particularly noted that,despite the severity and duration of the symptoms,most of the workers appeared to be in good health.The factory surgeon had noted that women gained alot of weight (in some cases as much as two stone)as soon as they began to work in the plant ; lesser

gains in weight were noted in some of the men. Redcells and haemoglobin in both sexes were some 10%below the accepted normal and the numbers of whitecells were above the normal. STEWART and WiTTS

say however that there is a good deal to be learntabout frequency distribution of hsematological datain factory populations and that there is no patho-gnomonic change in the blood-counts of the carbontetrachloride workers. Blood-urea, serum bilirubinand phosphatase, and plasma-proteins were all withinnormal limits. According to the Takata-Ara testliver efficiency was not impaired. The total fats,

, fatty acids and cholesterol of the plasma were deter-mined in 9 men and 12 women and these were alsonormal. Barium meals, which were given to 25

people, revealed a characteristic irritability of thealimentary tract shown by spasm of various parts ofthe gut and a rapid passage of the meal during thefirst 6 hours. Fractional test-meals in 20 cases

showed hyperchlorhydria in 11, hypochlorhydria in3 and excess of mucus in 3 cases. The most severe

hyperchlorhydria was found in a man who had hada heavy exposure with severe nausea and vomiting5 days before. All those with well-marked hyper-chlorhydria showed radiological changes but thesewere also found with hypochlorhydria. Gastroscopywas done in 16 cases and in 9 of them the stomach

musculature was found to be tonically contracted and,unduly liable to intense and long-continued spasm,a finding which was consistent with the radiographicappearances. Examination of the eyes in 15 casesrevealed none of the changes, such as toxic amblyopiaor restriction of the visual fields, which have beenascribed by WIRTSCHAFTER 2 to the effects of carbontetrachloride.

"

In 1942 ELKINS 3 noted similar symptoms in carbontetrachloride workers and thought that they reflectedthe early stage of liver damage. But chronic liver

changes rarely follow exposure to CCl4 and animalstudies suggest the reason. To bring about per-manent liver damage in animals each dose must belarge enough to affect the liver and the doses mustbe repeated at short intervals. In the rat, forinstance, the liver necrosis set up is repaired com-pletely in 14 days, and if the intervals between dosesof CCl4 are longer than this period the drug can beadministered indefinitely without producing per-manent liver damage. STEWART and WITTS pointout the resemblance of carbon tetrachloride poisoningto postanaesthetic symptoms and draw attention tothe chemical relationship, between carbon tetra-chloride (CC1J, chloroform (CHCI3) and ethylchloride (C2HsCI). They regard it as possible thatboth the mental hebetude. and the gastrointes-tinal upset are due to the narcotic action of CCl4on the central nervous system. They recall thatBEATTIE, BRow and LONG 5 in 1930 showed thatchloroform has a sharply localised effect on the

sympathetic centres in the hypothalamus, andinstance the striking similarity between the symptomsof carbon tetrachloride intoxication and the gastro-intestinal effects produced by stimulation of the

hypothalamus. " Some of the protocols ofCrrsHlNa’sexperiments, in which the hypothalamus was

stimulated by the injection of pituitrin and

acetylcholine into the lateral ventricles, could be

applied without alteration to carbon tetrachloridesickness."

SCIENTIFIC METHODIN a full-day debate on April 19 the House of

Commons applauded the successful application ofscientific research to the prosecution of the war andendorsed the Government’s proposal to spend moremoney on its application to commerce and industrywhen the war is over. Commoners had before thema useful statement (Cmd. 6514, 2d.) on existingGovernment organisation for this purpose. Onanother page Medicus MP tells of the wide scope ofthe debate. Belief is slowly but surely gainingground in scientific method as the only possible basisfor an ordered life, individual or national. Theimminent passing of the Education Bill raises a hopethat all the school-children of the future will betaught to observe the relation of cause and effect, andacquire the habit of weighing and measuring accur-ately. As the Times remarks, research in educationis necessary for the education even of research-workers.

2. Wirtschafter, Z. T. Amer. J. publ. Hlth, 1933, 23, 1035.3. Elkins, H. B. J. industr. Hyg. 1942, 24, 233.4. Bollmann, J. L. and Mann, F. G. Ann. intern. Med. 1931, 5, 699.

Cameron, G. R. and Karunaratue, W. A. E. J. Path. Bact.1936, 42, 1.

5. Beattie, J., Brow, G. R. and Long, C. N. L. Proc. roy. Soc. B.1930, 106, 253.

572 VASOCONSTRICTOR SUBSTANCES AND SHOCK

Annotations

A WATER POLICY

THE White Paper presented to Parliament last week 1by the Ministers of Health and Agriculture is worthy ofits subject. Fire, air, earth and water, the raw materialsof human activity, each have their own immutablecharacters which we must recognise and understand ifthey are to serve the changing face of civilisation.Water is particularly intractable. It is bulky and cannotbe compressed for storage ; it is heavy and costly tocarry, except downhill ; it is most plentiful in placeswhere it is not immediately needed ; and being the uni-versal solvent it picks up anywhere and everywherethings that men and animals want to get rid of. Thedistribution of water has been a pioneer service andhas suffered because the unit of action was the parish ortown. Private owiiers have had the disposal of the airabove and of the waters beneath their holdings ; anyonecould dig a well or sink a mine, at the cost of depletingor polluting his neighbour’s supply. Despite all this

opportunity for grab or first -come -first -served the storyof the thousand and one water undertakings has been aheartening one, and the 26 undertakers who supply halfthe population of England and Wales have set a fineprecedent of public utility, whereas the legislativeauthority has needed the stimulus of cholera (as in 1844)or unprecedented drought (as in 1934) to move it toaction.And now under the threat of another drought, and the

feeling that the tempo was not quick enough to keep upwith claims of housing and agriculture that will be on usalmost before we have time to think, Parliament is

rightly insisting on its health ministers taking the over-sight of its water. The rural waterless population hasgrown vocal, stimulated to fresh hope by the nearnessof aerodrome or war-time factory that has brought someof them a piped supply. The Exchequer is now to beasked for a grant to make this extension, with its com-panion sewerage, available throughout the country. Atthe same time, the central committee, which came intobeing in 1937 under the chairmanship of Lord Milne toadvise the Government about water, is to have officialstatus and the right to initiate policy. The regionaladvisory committees, which have already harnessed

many undertakings in teams, are also to have their handsstrengthened by the right to demand the facts and

figures they need to make their advice effective. Thedemocratic principle will nevertheless still hold and thelocal authorities will remain the custodians of their

ratepayers’ interests ; but Whitehall will have its eye onthem, by way of continuous inspection and survey.Water undertakers that fail to reach the desired standardwill be relieved of their charge. Finally, and perhapsfundamentally, the Geological Survey will get on with itstask of discovering the water-bearing rocks and how theycan best be tapped.

In all this, there is no claim for control on its ownaccount, or change for the sake of change. In fact theMinister has said in so many words that money is only tobe expended on benefits which we do not yet enjoy.VASOCONSTRICTOR SUBSTANCES AND SHOCKWE have already referred to Page and Abell’s observa-

tions 2 on the constriction of mesenteric and cutaneousblood-vessels in anaesthetised rabbits and cats which hadbeen bled or injured by application of tourniquets to thehind limbs. They reported that the arteries and veinsconstricted within an hour of trauma, relaxing onlyshortly before death ; but blood-now was not seen to beinterrupted. Since then they. have described 3 similar1. A National Water Policy. Cmd. 6515. HMSO. 6d.2. Page, I. H. and Abell, R.G. J. exp. Med. 1943, 77, 215 ; see

Lancet, 1943, i, 783.3. Abell, R. G. and Page, T. H. Surg. Gynec. Obstet. 1943, 77, 348.

findings in cats and dogs burnt by immersion of theirlimbs in boiling water or by exposure to steam. Thevasoconstriction of the small arteries and arterioles in themesentery which usually followed scalding or burningwas rather more intense than that seen after haemorrhageor the application of tourniquets, and was associated withslowing of the blood-flow and sometimes stasis in thecapillaries and venules. The arteriovenous anastomosesalso constricted—occasionally before the parent vessels-and as a rule the larger veins were narrowed too.Such a constriction, if it occurs throughout the

splanchnic region after injury and is accompanied bygeneralised cutaneous vasoconstriction, must be an

important cause of the diminution of venous return whichis evident in shock. The mechanism by which it is

brought about experimentally is still unexplained. It

may be mediated by the vasoconstrictor nerves or’ byhumoral agents, or (Page thinks) it may be to someextent a passive effect of reduction of blood-volume bythe injurious stimuli used. Its persistence suggestedthat it is partly due to the formation and liberation of avasoconstrictor substance, and this hypothesis has beentested. Using as indicator the rate of flow through thevessels of the isolated rabbit’s ear perfused withcalcium-free Ringer solution or plasma, Page 4 producedevidence that within half an hour of severe trauma-application of tourniquets to the limbs, haemorrhage,stripping of the intestines, and burning-the plasma ofdogs contains such a substance. His claim that thisis distinct from the vasoconstrictor substance found inserum (human or canine), and in the plasma of hyper-tensive man and dog, and is also distinct from histamine,’

I

needs confirmation. Its development does not seem todepend on the integrity of the nerve-supply of the

kidneys, or on the presence of the kidneys themselves orthe adrenal glands, or the thoracic or lumbar segments ofthe spinal cord ; but its site of formation has not beendemonstrated. Sapirstein, Southard and Ooden,5 Hamil.ton and Collins,6 and Huidobro and Braun.Menendez 7have shown that after haemorrhage the blood-streamcontains a pressor substance originating in the kidneys.The relative importance of the pressor substance derivedfrom the kidneys and the vasoconstrictor substanceformed in some other tissue has still to be determined, andso have the rôle of the autonomic nervous system and thebearing of these observations on shock in man.

PLANT VIRUSES

’1’mn destruction of the type of the first edition ofBawden’s valuable treatise on the plant viruses, duringthe invasion of the Netherlands, has resulted in the

happy birth of a second edition.8 The work hasbeen entirely revised and incorporates his own recentcontributions in this field of study as well as thoseof investigators abroad. X rays and the electronmicroscope have shown that the molecular complexof most plant viruses is elongated. For the tobaccomosaic virus the chemical nature has been estab-lished as a nucleoprotein, and the same is probablyalso true of the other viruses, though the evidence isless complete. There is now no doubt that thesenucleoproteins are the antigens specific to virus-infectedplants and because of their specificity the serologicalreactions constitute a satisfactory and rapid means ofidentifying viruses. The fact that a mild strain of onevirus can protect against the effect of infection by avirulent strain of the same virus affords an interestingparallel to vaccination ; but unfortunately, avirulent

4. Page, 1. H. Amer. J. Physiol. 1913, 139, 386.5. Sapirstein, L. A., Southard, F. D., Ogden, E. Proc. Soc. exp.

Biol. Med. 1942, 50, 320.6. Hamilton A. S. and Collins, D. A. Amer. J. Physiol. 1942, 136,

275.7. Huidobro and Braun-Menendez, E. Ibid, 1942, 137, 47.

Plant Viruses and Virus Diseases (2nd ed.). F. C. Bawden,head of the plant pathology department, Rothamsted Experi-mental Station. (Chronica Botanica Co. Pp. 294. $4.75.)