1
1301 technical assistance is threatening to fall to pieces for want of money. Firstly, the U.N. agencies only get their allotments on a yearly basis ; secondly, contributing countries have reduced their commitments and a 20% cut in all expenditure has had to be made. No-one who has examined the detailed reports of W.H.O. and F.A.O. would dispute that the funds have been well administered and almost all the money profitably invested in schemes likely to advance the health and economic prosperity of mankind. Underdeveloped countries are, after a lag, seeking to make the full possible use of available aid, so that requests for help now exceed resources. Both in education and in development, long-term schemes are likely to do the most good ; yet, against an uncertain financial back- ground, the risk of starting something which may soon be cut ofE by budget restrictions is a real one. Worries of this kind may lead to the appointment of a specialist for a brief period to give immediate help in a particular plan, when it would be wiser to recruit a man prepared for a longer stay and able to give detailed supervision to the whole project. There is no solution to these difficulties except a greater degree of financial stability. Here the onus lies on public opinion in the contributing countries ; and it is disturbing to read 33 that the British contribution to this U.N. work was cut from 2-1 million dollars in 1951 to 1-3 million dollars in 1952. This seems a trivial economy ; and if other countries follow suit, the efforts to help the govern- ments of the backward countries of the world to raise their people above primitive poverty will be seriously prejudiced. 33. Planning, 1952, 19, 61. 34. See Lancet, Nov. 14, 1953, pp. 1027, 1039. Dundee, J. W., Gray, T. C., Mesham, P. R., Scott, W. E. B. Brit. med. J. Dec. 5, 1953, p. 1237. Dundee, J. W., Scott, W. E. B., Mesham, P. R. Ibid, p. 1244. Smith, A., Fairer, J. G. Ibid, p. 1247. 35. Friend, D. G., Cummins, J. F. J. Amer. med. Ass. 1953, 153, 480. 36. Borison, H. L., Wang, S. C. Pharmacol. Rev. 1953, 5, 193. A NEW ANTI-EMETIC CHLORPROMAZINE hydrochloride (‘ Largactil ’), a vigorous young near-relation of the anti-histamine substances, is so far best known in this country for its power to bring about artificial hibernation 34 ; and this action was discussed at a meeting of the Royal Society of Medicine reported on p. 1294 of this issue. On the Continent chlorpromazine hydrochloride has also given promising results in the treatment of psychiatric dis- orders. But its versatility does not end there ; for it has a powerful -anti-emetic action. Friend and Cummins 35 have treated seventy hospital patients with vomiting from such varied causes as uraemia, carcinomatosis, and pregnancy, and the effect of drugs such as aureomycin, morphine, and proto- veratrine, and the disulfiram-alcohol reaction. The drug was given intramuscularly or orally in doses of 25-50 mg. three or four times a day. In almost all cases the vomiting ceased promptly ; and side-effects were rare, consisting only of mild drowsiness, dryness of the mouth, and flushing. Yet the other pharmacological effects of this drug suggest ’that its use as an anti-emetic will not long be untroubled by side-effects. It is a ganglion- blocking agent with anticholinergic and powerful sympatholytic and spasmolytic actions ; it acts on the respiratory centre, slowing the rate and augmenting the amplitude of breathing ; it blocks thermoregulation by a direct action on the hypothalamus, and possibly acts indirectly on the hypophysis, as is indicated by a modification of postoperative eosinopenia ; and it potentiates the action of many drugs, notably the barbiturates, pethidine, nitrous oxide, volatile anæs- thetics, procaine amide, and curare. The basis of anti-emetic activity in general has been much clarified by the work of Borison and Wang.36 These workers show that drugs such as apomorphine, to which have been attributed a " central " stimulant action on the vomiting centre, do not in fact act directly on the centre. The emetic response is now known to be carried to the centre in a reflex arc which is initiated at what has been called a " chemoreceptor trigger zone." This receptor is situated on the surface of the medulla outside the central nervous system, and is activated not only by drugs but also by the vestibular stimuli concerned in the production of motion sickness.37 The nature of the trans- mitter is not known, but it is apparently not acetyl- choline.36 If anti-emetic drugs act-as conceivably they may-by blocking transmission at this site, it is unlikely that a specific anti-emetic will be found until the trans- mitter substance is identified. Moreover, Borison and Wang believe that the central vomiting mechanism cannot be depressed without concurrent depression of closely associated vital functions involved in the emetic syndrome. Borison and Wang give a conservative valediction : " The most intelligent therapeutic approach to- clinical vomiting is elimination of the specific cause rather than the general effect." 37. Wang, S. C., Chinn, H. I. Fed. Proc. 1952, 11, 400. 38. Franks, L. M. J. Path. Bact. 1953, 66, 91. 39. Batson, O. V. Ann. Surg. 1940, 112, 138. 40. Acta psychiat., Kbh. 1953, 28, 123. SPREAD OF PROSTATIC CANCER IT is well known that cancer of the prostate often metastasises to the bones of the vertebral column, but how the tumour emboli get there is something of a mystery. The normal channel of venous flow from the prostate is via the inferior vena cava ; and it might be expected therefore that secondary growths would first appear in the lungs, by arrest of emboli in passage through the pulmonary capillaries. It has been argued that minute emboli might sometimes be filtered through the lungs back into the systemic circulation and so reach the bones. Certainly this might happen ; but a less tortuous route would seem more probable. Franks 38 has reinvestigated this question, taking as his starting-point a suggestion by Batson 39 in 1940 that the prostatic veins and the vertebral venous system might be more directly linked. By an opaque-injection method Franks has proved that there is a direct link between the prostatic venous plexus and that of the vertebrae ; and it seems from this work that the distri- bution of bony metastases in prostatic cancer can most reasonably be explained by the passage of tumour emboli along this channel, which by-passes the caval, portal, and pulmonary circulations. Batson originally suggested that obstruction of the inferior vena cava by increased intra-abdominal pressure could predispose to diversion of blood-flow from the pelvis into the vertebral venous system. The possibility of similar factors in the distribution of venous emboli from prostatic cancer raises interesting practical questions. Coughing, straining, and increased intra-abdominal pres- sure from other causes may turn out to be dangerous to the patient with prostatic cancer. PRIMITIVE LEVELS IN SCHIZOPHRENIA WHEN the nervous system degenerates, the highest levels of function, being those acquired latest in the history of evolution, perish first. Dr. Ada Glynn 40 argues that a parallel process is evident in the decay of the mind in schizophrenia-that, as disintegration proceeds, primitive mental mechanisms appear and supersede rational thinking. It is an engaging theory, and she brings forward some well-known ethnological findings to support it. Thus, it is a common belief, in primitive cultures, that inanimate objects influence people and events. Such objects may be rocks, trees, weapons, leaves, animals-or words, especially numbers and proper names. The primitive tribesman, it is said, does not distinguish himself sharply from the rest of the

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Page 1: SPREAD OF PROSTATIC CANCER

1301

technical assistance is threatening to fall to pieces forwant of money. Firstly, the U.N. agencies only get theirallotments on a yearly basis ; secondly, contributingcountries have reduced their commitments and a 20%cut in all expenditure has had to be made. No-one whohas examined the detailed reports of W.H.O. and F.A.O.would dispute that the funds have been well administeredand almost all the money profitably invested in schemeslikely to advance the health and economic prosperity ofmankind. Underdeveloped countries are, after a lag,seeking to make the full possible use of available aid, so thatrequests for help now exceed resources. Both in educationand in development, long-term schemes are likely to dothe most good ; yet, against an uncertain financial back-ground, the risk of starting something which may soon becut ofE by budget restrictions is a real one. Worries ofthis kind may lead to the appointment of a specialist fora brief period to give immediate help in a particular plan,when it would be wiser to recruit a man prepared for alonger stay and able to give detailed supervision to thewhole project.There is no solution to these difficulties except a greater

degree of financial stability. Here the onus lies on publicopinion in the contributing countries ; and it is disturbingto read 33 that the British contribution to this U.N. workwas cut from 2-1 million dollars in 1951 to 1-3 milliondollars in 1952. This seems a trivial economy ; and ifother countries follow suit, the efforts to help the govern-ments of the backward countries of the world to raisetheir people above primitive poverty will be seriouslyprejudiced.

33. Planning, 1952, 19, 61.34. See Lancet, Nov. 14, 1953, pp. 1027, 1039. Dundee, J. W.,

Gray, T. C., Mesham, P. R., Scott, W. E. B. Brit. med. J.Dec. 5, 1953, p. 1237. Dundee, J. W., Scott, W. E. B.,Mesham, P. R. Ibid, p. 1244. Smith, A., Fairer, J. G.Ibid, p. 1247.

35. Friend, D. G., Cummins, J. F. J. Amer. med. Ass. 1953, 153, 480.36. Borison, H. L., Wang, S. C. Pharmacol. Rev. 1953, 5, 193.

A NEW ANTI-EMETIC

CHLORPROMAZINE hydrochloride (‘ Largactil ’), a

vigorous young near-relation of the anti-histaminesubstances, is so far best known in this country for itspower to bring about artificial hibernation 34 ; and thisaction was discussed at a meeting of the Royal Societyof Medicine reported on p. 1294 of this issue. On theContinent chlorpromazine hydrochloride has also givenpromising results in the treatment of psychiatric dis-orders. But its versatility does not end there ; for ithas a powerful -anti-emetic action.

Friend and Cummins 35 have treated seventy hospitalpatients with vomiting from such varied causes as

uraemia, carcinomatosis, and pregnancy, and theeffect of drugs such as aureomycin, morphine, and proto-veratrine, and the disulfiram-alcohol reaction. The drugwas given intramuscularly or orally in doses of 25-50mg. three or four times a day. In almost all cases the

vomiting ceased promptly ; and side-effects were rare,consisting only of mild drowsiness, dryness of the mouth,and flushing. Yet the other pharmacological effects ofthis drug suggest ’that its use as an anti-emetic will notlong be untroubled by side-effects. It is a ganglion-blocking agent with anticholinergic and powerfulsympatholytic and spasmolytic actions ; it acts on the

respiratory centre, slowing the rate and augmenting theamplitude of breathing ; it blocks thermoregulation bya direct action on the hypothalamus, and possibly actsindirectly on the hypophysis, as is indicated by amodification of postoperative eosinopenia ; and itpotentiates the action of many drugs, notably thebarbiturates, pethidine, nitrous oxide, volatile anæs-

thetics, procaine amide, and curare.The basis of anti-emetic activity in general has been

much clarified by the work of Borison and Wang.36 Theseworkers show that drugs such as apomorphine, to whichhave been attributed a " central " stimulant action on

the vomiting centre, do not in fact act directly on thecentre. The emetic response is now known to be carriedto the centre in a reflex arc which is initiated at what hasbeen called a

"

chemoreceptor trigger zone." This

receptor is situated on the surface of the medulla outsidethe central nervous system, and is activated not only bydrugs but also by the vestibular stimuli concerned in theproduction of motion sickness.37 The nature of the trans-mitter is not known, but it is apparently not acetyl-choline.36 If anti-emetic drugs act-as conceivably theymay-by blocking transmission at this site, it is unlikelythat a specific anti-emetic will be found until the trans-mitter substance is identified. Moreover, Borison andWang believe that the central vomiting mechanismcannot be depressed without concurrent depression of

closely associated vital functions involved in the emeticsyndrome. Borison and Wang give a conservativevalediction : " The most intelligent therapeutic approachto- clinical vomiting is elimination of the specific causerather than the general effect."

37. Wang, S. C., Chinn, H. I. Fed. Proc. 1952, 11, 400.38. Franks, L. M. J. Path. Bact. 1953, 66, 91.39. Batson, O. V. Ann. Surg. 1940, 112, 138.40. Acta psychiat., Kbh. 1953, 28, 123.

SPREAD OF PROSTATIC CANCER

IT is well known that cancer of the prostate oftenmetastasises to the bones of the vertebral column, buthow the tumour emboli get there is something of a mystery.The normal channel of venous flow from the prostateis via the inferior vena cava ; and it might be expectedtherefore that secondary growths would first appear inthe lungs, by arrest of emboli in passage through thepulmonary capillaries. It has been argued that minuteemboli might sometimes be filtered through the lungsback into the systemic circulation and so reach thebones. Certainly this might happen ; but a less tortuousroute would seem more probable.

Franks 38 has reinvestigated this question, taking ashis starting-point a suggestion by Batson 39 in 1940 thatthe prostatic veins and the vertebral venous systemmight be more directly linked. By an opaque-injectionmethod Franks has proved that there is a direct linkbetween the prostatic venous plexus and that of thevertebrae ; and it seems from this work that the distri-bution of bony metastases in prostatic cancer can mostreasonably be explained by the passage of tumour embolialong this channel, which by-passes the caval, portal,and pulmonary circulations.

Batson originally suggested that obstruction of theinferior vena cava by increased intra-abdominal pressurecould predispose to diversion of blood-flow from the

pelvis into the vertebral venous system. The possibilityof similar factors in the distribution of venous emboli fromprostatic cancer raises interesting practical questions.Coughing, straining, and increased intra-abdominal pres-sure from other causes may turn out to be dangerousto the patient with prostatic cancer.

PRIMITIVE LEVELS IN SCHIZOPHRENIA

WHEN the nervous system degenerates, the highestlevels of function, being those acquired latest in the

history of evolution, perish first. Dr. Ada Glynn 40argues that a parallel process is evident in the decayof the mind in schizophrenia-that, as disintegrationproceeds, primitive mental mechanisms appear and

supersede rational thinking. It is an engaging theory,and she brings forward some well-known ethnologicalfindings to support it. Thus, it is a common belief, inprimitive cultures, that inanimate objects influence

people and events. Such objects may be rocks, trees,weapons, leaves, animals-or words, especially numbersand proper names. The primitive tribesman, it is said,does not distinguish himself sharply from the rest of the