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the diet small amounts of animal foods or liver-extract. The essential principle was later shown to bethe cobalt-containing vitamin B12.25

So far there have been few comparative studies onadults receiving mixed animal and vegetable diets, andpure vegetable diets. BoYD ORR and GILKS 26 comparedthe diets of two African tribes-one meat-eating, theother vegetarian-and found that the meat-eaterswere taller and healthier and had a lower prevalenceof arzaemia than the vegetarians. TAYLOR andCHH]UTTANI 27 found that the hospital-admission ratefor anaemia was twenty-two times higher amongvegetarian Indian soldiers than among their meat-eating comrades. WILLS 28 ascribed kwashiorkor inAfrican infants entirely to deficiency of animal

protein. On the other hand investigations inAmerica 29-32 have indicated that vegetarians, althoughthey may be underweight and below average height,28and their intake may provide less than the recom-mended amount of calories, are not especially proneto ill health or haematological abnormality. HARDINGEand STARE 33 have compared 112 vegetarians and88 meat-eating adolescents and adults, includingpregnant women. The vegetarians were subdivided.into those who took milk and eggs and those who were

- 9pure " vegetarians. The meat-eating adolescentsate significantly more protein than did adolescentsin the two vegetarian groups ; but there were no

biochemical, haematological, or clinical differencesbetween any of the groups, except that the purevegetarians weighed on the average 20 lb. less thanmembers of the other groups. The same workers 34have since reported that the serum-cholesterol levelsin adult vegetarians were lower than those of adultmeat-eaters ; the levels in " pure " vegetarians werelowest of all, although this group partook freely ofvegetable fat. HARDiNGrE and STARE conclude thatthe serum-cholesterol level is more closely correlatedwith the intake of animal than of vegetable fat.The reported differences in the effects of vegetarian

diets on health in America and in Africa and Asia are

probably due to the far greater stresses on the

haemopoietic system in tropical countries amongeconomically poor peoples who are liable to debilitatingdisease. In general, vegetarians in the West are

reasonably well-to-do, taking a close interest in theirnutritional state (HARDINGE and STARE noted thattheir vegetarians were highly " protein-conscious ") ;and they are relatively free from chronic endemicdisease. Discussing the diet of Indian troops,MARRIOTT 35 observed : " Vegetarian or lactovege-tarian diets may be adequate in central India butare not sufficient in areas where men’s red cells are

destroyed by repeated malaria or drained by hook-worms. Such diets result in little or no bodily reservesof haemopoietic materials."25. Hartman, A. M., Dryden, L. P., Cary, C. A. Arch. Biochem.

1949. 23, 165.26. Orr, J. B., Gilks. J. L. Studies in Nutrition : The Physique

and Health of two African Tribes. Spec. Rep. Ser. Med. Res.Coun., Lond.. no. 135. H.M. Stationery Office, 1931.

27. Taylor, G. F., Chhuttani, P. N. Brit. med. J. 1945, i, 800.28. Wills, L. Brit. J. Nutr. 1951, 5, 265.29. Jaffa, M. E. Nutrition Investigations among fruitarians and

the Chinese. U.S. Department of Agriculture Bulletin, no. 107,1901.

30. Foote, R., Eppright, E. S. J. Amer. diet. Ass. 1940, 16, 222.31. Mirone, L. Science, 1950, 111, 673.32. Oldham, H., Shaft, B. B. J. Amer. diet. Ass. 1951. 27, 847.33. Hardinge, M. G., Stare, F. J. J. clin. Nutr. 1954, 2, 73.34. Hardinge, M. G., Stare, F. J. Ibid, p. 83.35. Marriott, H. L. Lancet, 1945, i, 679.

Annotations

SCHIZOPHRENIA AND ADRENOCHROME

MESCALINE and adrenaline have a similar chemicalstructure, and among the many hundreds of substancesintermediate between them, some-without causing ZD

clouding of consciousness, confusion, or gross physio-logical disturbances-produce psychological states

resembling those found in schizophrenia. Dr. AbramHoffer, Dr. Humphrey Osmond, and Dr. John Smythies,lat the Saskatchewan Hospital, ’report the result of a

year’s study of the effects-in trials made on themselvesand other volunteers-of one of these, adrenochrome.In Hoffer’s case the mental changes induced by the drugincluded overactivity, poor judgment, and lack of

insight into the cause of his state of mind. Anothersubject (his wife) developed a condition indistinguishablefrom endogenous depression, lasting 4 days ; she, too,was unable to relate her change of mood to the injection.It is suggested that the prolonged effect in her case wasdue to impaired inactivation of adrenochrome, the resultof an attack of infective hepatitis some years before. InOsmond the drug produced subjective changes of a moreschizoid type : colours and lighting seemed brighter,pictures became’ livelier, and when he closed his eyespatterns of coloured dots appeared. He was unwillingto respond to the questions put to him by his fellowinvestigators, felt cut off from other people, and had nointerest in the experiment. His detachment from otherpeople was such that he did not care whether or not theywould be knocked down by the car in which he wastravelling. He suspected a man of watching him covertly,speculated as to whether he was a plant or a stone-insteadof a person, and had what he described as a

"

glass-wall-other-side-of-the-barrier " feeling. His colleagues reportthat he was negativistic, preoccupied with inanimateobjects, distractable, and anxious. The investigatorsconclude from their experiences that adrenochrome

produces a " model psychosis," lasting at least 24 hours

and sometimes longer, in which the subject quickly losesinsight, and is unable to relate his experiences to theinjection he has received. This is the first time that asubstance which possibly occurs in the human body hasbeen found to be active in this way. How it acta is notyet clear, but it is said to inhibit both aerobic andanaerobic respiration of brain tissue in the Warburgapparatus. This could be partly explained by its

inhibiting the enzyme hexokinase, and hence theentire oxidative system of brain tissue, starting with-glucose. -

Hoffer and his colleagues also gave intravenous

injections of adrenochrome to some epileptic volunteers.In those with electro-encephalograms (E.E.G.) showingdefinite cerebral dysrhythmia, the generalised arrhythmiaincreased greatly within half an hour, and focal activitvbecame more pronounced. In epileptics with a normalE.E.G. adrenochrome brought out the epileptic arrhythmiamore effectively than leptazol. In a schizophrenicpatient with an essentially normal E.E.G., dysrhythmiadeveloped after adrenochrome. They are now usingadrenochrome as a routine to establish the diagnosis ofepilepsy.

1. J. ment. Sci. 1954, 100, 29.

TREATMENT OF RENAL FAILURE WITH ALKALIS

THE metabolic acidosis of chronic renal failure isassociated with an increased plasma level of phosphate,sulphate, and unidentified anions. As in other types ofmetabolic acidosis the replacement of bicarbonate byother anions tends to reduce the plasma pH ; but thistendency is more or less compensated by overbreathing,which lowers the free carbonic acid to an extent which

231

keeps the ratio BHCO3/HsCO3 higher than would beexpected from the primary fall in BHCO3. The over-

breathing is very obvious, and in patients who remainalert it causes distress ; but direct treatment of theacidosis by alkalis has not been greatly practised, partlybecause these patients do not commonly have a deficitof base, as judged by plasma levels, and partly for fearof provoking tetany.In the past few years there has been renewed interest

in direct treatment of the electrolyte disturbancesassociated with renal failure. The artificial kidney givesan opportunity of correcting electrolyte disorders paripassu with the removal of non-protein nitrogen ; but itsuse in irreversible renal failure is scarcely justified. Tissueanalyses have indicated that, despite the normal plasmalevels of sodium and potassium found in most patientswith renal failure, there is often a tissue deficit of base.!A base deficit can be corrected by giving sodium bicar-bonate or lactate. That part of the metabolic acidosiswhich is due to base deficit should respond to such treat-ment ; but the removal of anions would not be accom-plished in this way, except by an alkaline diuresis, fromwhich the failing kidney is debarred since its plasticityof response to change in body-fluid pH seems to be aslimited as its other homoeostatic responses.Theoretical as well as practical interest thus attaches

to recent attempts 2 3 to treat the acidosis of renal failureby direct administration of alkali. Intravenous hyper-tonic sodium lactate has been given to patients in coma,who have recovered consciousness ; and for consciouspatients a regime of oral hypertonic sodium lactate hasbeen used.3 Gastro-intestinal irritation, it is said, passesoff in a few days, after which alkali can be given more orless indefinitely. Considerable success is claimed for thismode of treatment, even though it cannot influence renalstructural change ; in some patients improvement is nodoubt related to correction of a latent sodium depletion,without overt signs of dehydration, and in these theblood-urea may fall. In some patients calcium gluconatehas to be given to control tetany, and in others potassiumsalts are given in small doses by mouth, with frequentchecking of the plasma-potassium level.

1. Porter, R. R., Neubauer, R. A., Fischer, E., Young, N. F. Trans.Amer. climat. (clin.) Ass. 1950, 62, 239.

2. Salvesen, H. A. Acta med. scand. 1951, suppl. 259, p. 75.3. Neubauer, R. A. Amer. J. med. Sci. 1954, 227, 628.4. Meigs, J. V., Cass, J. W. Amer. J. Obstet. Gynec. 1937, 33, 249.5. Meigs, J. V. Ibid, 1954, 67, 962.6. Funck-Brentano, P. Pr. Méd. 1949, 57, 341.

MEIGS’S SYNDROME

SmrcE Meigs and Cass 4 reported 7 cases of fibroma ofthe ovary with ascites and hydrothorax, which werecured by removal of the fibroma, many examples of thiscondition have been recorded. Meigs 5 has lately reviewed84 cases of the syndrome which is now generally knownby his name. He begins by giving credit to the severalauthors who, over half a century ago, described thecondition, and he willingly accepts a suggestion byPunck-Brentano 6 that the condition should be renamedthe Demons-Meigs syndrome. It is unlikely, however,that this proposal will be widely accepted, for the claimsto be made for the works of Cullingworth, in 1879, andLawson Tait, in 1892, rival those of Demons (1887 andlater); all in all, it seems best to accept the universallyrecognised " Meigs’s syndrome."Meigs 5 now seeks to define the limits of the syndrome

-for increasing numbers of cases are being recordedwhich exhibit variations from the original. It has becomeclear that peritoneal and pleural effusions are found asoccasional complications not only of solid ovarian tumoursbut of ovarian cysts, and even endometriosis and uterinefibroids, and that pleural effusion can complicate a

malignant ascites in the abdomen, without extension ofthe cancer to the chest. In time the true frequency ofsuch complications will be known. For the present,

Meigs would restrict the term to effusions associatedwith benign solid ovarian tumours, comprising fibromata,granulosa-cell and theca-cell tumours (all of which Willis 7holds to belong to the same family), and the mysteriousBrenner tumour ; and this seems good advice.Two fascinating problems remain to be solved : the

mode of production of the fluid and its pathway fromthe peritoneum to the pleura. There can be no doubtthat the source of the effusion is the tumour itself, forremoval of the tumour results in cure ; and Meigs hasproved the two effusions to be identical. Many now holdthat the production of ascites depends on oedema andwatery degeneration within the solid tumour itself. Afairly large tumour is required, for ascites rarely occurswith fibromas of less than 6 cm. diameter. Torsion,though it may cause degeneration and thereby initiatethe effusion, is not a sufficient explanation in itself, forit is rarely found, and severe torsion of a cyst does notcommonly result in a comparable effusion. In the caseof the cyst, the presence of a non-permeable capsulemight prevent the formation of an effusion. It is stilluncertain whether the cell-type plays an essential partin the production of the fluid. Thus, no instances haveso far been recorded in association with virilising tumours,though Novak 8 states that the arrhenoblastoma maygrow to the requisite size and that it often undergoescystic degeneration ; and it may be of low malignancy.It will be interesting to see whether in time this type oftumour is also reported in association with the syndrome.The solution to the problem of the hydrothorax is

also not yet fully clear. Of the early hypotheses some,such as pressure on the azygos vein and the " alarmreaction " of Selye, have been discarded. The twotheories which survive acknowledge that the chesteffusion arises by passage across the diaphragm from theperitoneal sac but differ in respect of the pathway usedby the fluid. Those who believe the route to be a lymph-atic one have to explain the comparative rarity of thecondition rather than its occurrence. Estimates of theincidence of ascites with fibroma of the ovary vary butthey average about 20%. The incidence of pleuraleffusion is certainly much less ; in Dockerty’s series 9it was 0-7%. In a letter published in this issue Mr.Parker notes the revival of the theory of a direct com-munication between the two sacs and points out thatthere is now good evidence for the existence of a patentchannel, at least in some cases. He makes the newproposal that the communication may sometimes arisethrough rupture of a weak point in the diaphragm. Buthe does not suggest that a direct channel is present in allcases.

It now seems certain that the presence of a hydro-thorax as a complication of ascites is in no way specificto Meigs’s syndrome. Strictly comparable conditionsdo not often exist in other disease processes, but verysimilar findings are recorded in cirrhosis of the liver.In this disease, so commonly producing ascites, Licht-man 10 estimates the incidence of pleural effusion to bebetween 1% and 3%. Frothingham" describes a casewhich is very similar to many examples of Meigs’ssyndrome before operation ; and Alexander James,12 aslong ago as 1899, described a curious case of cirrhosiswith ascites and right pleural effusion in which a com-munication was thought to exist between the rightpleura and the peritoneal cavity, inasmuch as tapping thepleura emptied the abdomen and, in fact, seemed to bemore successful than paracentesis abdominis. Further

7. Willis, R. A. Pathology of Tumours. London, 1948 ; p. 491.8. Novak, E. Gynecological and Obstetrical Pathology. Phila-

delphia and London, 1952 ; p. 427.9. Dockerty, M. B., Masson, J. C. Amer. J. Obstet. Gynec. 1944.

47, 741.10. Lichtman, S. S. Diseases of the Liver, Gall-bladder and Bile-

ducts. London, 1949.11. Frothingham, J. R. New Engl. J. med. 1942, 226, 679.12. James, A. Trans. med.-chir. Soc. Edinb. 1899, 18, 191.