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575 bleeding and toxcemia. He quotes McDowell who found the suprarenals are exhausted by cold. He concludes that although from the experimental point of view toxaemia is not yet accepted as a cause of shock, yet clinically it seems to be an important factor. Although, as Dale and Laidlaw have pointed out, there is a close resemblance between histamine shock and the shock produced by muscle trauma, in wound shock unfortunately " direct methods have failed to demonstrate a depressor (shock-causing) substance in the blood of a shocked animal" (Smith 5) . In burns, however, direct proof was also lacking. In histamine shock, anyway, an increased demand on the suprarenals seems to be recognised (see Wilson). Bleeding into tissues or the intestines, I suggest, probably acts through its " foreign " (because denatured) protein somehow like peptone, giving rise to an antigen-antibody reaction, and thus also exhausts the adrenals. Selye in Toronto found hyperplasia of the adrenal cortex in animals dying of surgical shock. He called it the " alarm-reaction " of the adrenals. But there are more elementary relations between cell-injury and the adrenals. One of the cardinal features of cell-injury is the interference with " selec- tive permeability," manifesting itself by loss of intra- cellular potassium and phosphate and the entry of the antagonistic sodium-chloride group into the injured cell, and by loss of electric potential (Keller and co-workers 7). This occurs under the influence of histamine, narcotics, direct cell-injury (burns), oxygen-deficiency, loss of heat, exertion, and so on (Dale, Eppinger’s " ser6se Entziindung "). In all these conditions cortical extract was able to reduce the disturbances of selective permeability (Kaunitz,Q Kaunitz and Selzer 9). As Einhauser 10 puts it, the cardinal function of the adrenal cortex appears to be its influence on the body cells in resisting the differ- ences in osmotic concentration. Cortical insufficiency causes loss of cell-potassium and the passage of the antagonistic group into the cell, and leads to cell- injury. Salt deficiency aggravates Addison’s disease. Primary loss of salt (McCance 11) may lead to a pronounced picture of cortical insufficiency. Not only loss of salt outwards but also loss into the injured cells, as Haden and Orr suggested for hypochloreemic azotasmia, seems to act in the same direction. In traumatic shock we can imagine a wandering of sodium chloride into all cells that are indirectly injured, especially in the traumatised tissue. Any kind of cell-injury associated with these electrolyte movements causes a relative cortical insufficiency, and may, if counter-mechanisms are not effective, finally lead by a vicious circle to fatal derangement of meta- bolism and the circulation. There is then, I think, a case for the administra- tion of cortical extract (or an active synthetic substance) in wound shock. It has been suggested already and I have seen its effect in a small number of cases. Similarly a state of cortical insufficiency apparently exists in some cases of gas poisoning (Yperite, Pyrodin, Lysocin, &c.). I am, Sir, yours faithfully, Queen’s Drive, N.4. H. POLLAK. 4. Dale, H. and Laidlaw, P. J. Physiol. 1918, 52, 355. 5. J. Pharmacol. 1927-28, 32, 465. 6. Selye, H. Klin. W schr. 1938, 17, 666. 7. Keller, R. Ibid, 1934, 13, 1041. 8. Kaunitz, H. Z. klin. Med. 1938, 134, 224. 9. Kaunitz and Selzer, L. Z. ges. exp. Med. 1938, 103, 664. 10. Einhauser, M. Klin. Wschr. 1939, 18, 423. 11. MeCance, R. A. Lancet, 1936, 1, 823. FRACTURED FEMUR IN CONVULSION THERAPY SiR,-In the article on fractures of the neck of the femur in convulsion therapy by Mr. Gissane, Dr. Blair and Mr. Rank in your issue of March 9, I was particularly interested in the first of their five con- clusions based on 4 such fractures (the eldest patient being aged 41) in a series of 96 cases. " Convulsion therapy," they say, " should not be used in elderly patients or in those who have had prolonged periods of inactivity, because the bones of such people have atrophied from disuse and readily fracture." I venture to disagree with that conclusion on several points. I have now treated over 160 cases with Cardiazol and in these there have been but 2 fractures, 1 of them reported elsewhere (Brit. med. J. 1939, 2). Of a recent series of over 80 cases that I have treated, 25 fell within the age-group 50-65 years, composed as follows: 50-55 years, 13 cases; 55-60 years, 8 cases; 60-65 years, 4 cases. In only one of these, a woman of 59, did a fracture occur-of the head of the left humerus. Most of the 25 cases between 50 and 65 had " prolonged periods of inactivity." Indeed, some of them had been practically bed-ridden for years. I think these facts speak for themselves. I also disagree with two other points in their article -namely, " that the intensity of the muscular con- tractions during these convulsions is the most important factor in the causation of the fractures"; and that the fit of cardiazol convulsion and that of idiopathic epilepsy " differ greatly in the intensity of the muscular contractions." From the study of the convulsions produced in approximately 3000 injections, the aetiology of cardiazol fractures to my mind is not the intensity of the muscular contractions acting on the alleged brittleness of bones in the elderly or in those who have had long periods of inactivity. The fractures appear to be due in most cases to the technique adopted during treatment. Details of the activities of the doctor and nurses before and while the patient is convulsing are usually lacking, but one gathers from reading different papers that such activi- ties are directed towards restraining the movements of the patient. This, in my opinion, is a definite mis- take ; the behaviour of the doctor and nurses during that period should be one of complete inactivity save for guarding against dislocation of the jaw. Any movement of the patient during that period (save the jaw movement) should be quite unrestrained, and it is by acting on that maxim that I believe the number of fractures in my series of cases have numbered no more than 2. The maxim was arrived at by consider- ing the difference in incidence of fractures in cardiazol therapy and in idiopathic epilepsy. Since I could see no difference in the intensity of the muscular con- tractions in the two types of convulsion, I concluded that fractures in idiopathic epilepsy are rare because in them there is seldom either opportunity or occasion for restraint-the convulsion is regarded as a matter of course and the various parts of the body are allowed to look after themselves, which they seem to do very successfully. This hypothesis was borne out in the lady of 59. Her fracture occurred most prob- ably as the result of restraint exerted on the affected region by a nurse who was new to cardiazol treatment. It is perhaps superfluous to recall how a limb in the tonic stage is no longer a limb in the ordinary sense of the term; it loses its flexibility and range of move- ment and becomes a rigid structure unyielding save to considerable external force. It is easy to see how a fracture can occur when to the muscle strains on the bone already present external restraint is added.
Transcript of FRACTURED FEMUR IN CONVULSION THERAPY
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bleeding and toxcemia. He quotes McDowell whofound the suprarenals are exhausted by cold. Heconcludes that although from the experimental pointof view toxaemia is not yet accepted as a cause of
shock, yet clinically it seems to be an importantfactor.Although, as Dale and Laidlaw have pointed out,
there is a close resemblance between histamine shockand the shock produced by muscle trauma, in woundshock unfortunately " direct methods have failed todemonstrate a depressor (shock-causing) substance inthe blood of a shocked animal" (Smith 5) . In burns,however, direct proof was also lacking. In histamineshock, anyway, an increased demand on thesuprarenals seems to be recognised (see Wilson).Bleeding into tissues or the intestines, I suggest,probably acts through its " foreign " (becausedenatured) protein somehow like peptone, giving riseto an antigen-antibody reaction, and thus alsoexhausts the adrenals.
Selye in Toronto found hyperplasia of the adrenalcortex in animals dying of surgical shock. He calledit the " alarm-reaction " of the adrenals.But there are more elementary relations between
cell-injury and the adrenals. One of the cardinalfeatures of cell-injury is the interference with " selec-tive permeability," manifesting itself by loss of intra-cellular potassium and phosphate and the entry of theantagonistic sodium-chloride group into the injuredcell, and by loss of electric potential (Keller andco-workers 7). This occurs under the influence ofhistamine, narcotics, direct cell-injury (burns),oxygen-deficiency, loss of heat, exertion, and so on(Dale, Eppinger’s " ser6se Entziindung "). In allthese conditions cortical extract was able to reducethe disturbances of selective permeability (Kaunitz,QKaunitz and Selzer 9). As Einhauser 10 puts it, thecardinal function of the adrenal cortex appears to beits influence on the body cells in resisting the differ-ences in osmotic concentration. Cortical insufficiencycauses loss of cell-potassium and the passage of theantagonistic group into the cell, and leads to cell-injury. Salt deficiency aggravates Addison’s disease.Primary loss of salt (McCance 11) may lead to a
pronounced picture of cortical insufficiency. Notonly loss of salt outwards but also loss into the injuredcells, as Haden and Orr suggested for hypochloreemicazotasmia, seems to act in the same direction. Intraumatic shock we can imagine a wandering ofsodium chloride into all cells that are indirectlyinjured, especially in the traumatised tissue. Anykind of cell-injury associated with these electrolytemovements causes a relative cortical insufficiency, andmay, if counter-mechanisms are not effective, finallylead by a vicious circle to fatal derangement of meta-bolism and the circulation.
There is then, I think, a case for the administra-tion of cortical extract (or an active syntheticsubstance) in wound shock. It has been suggestedalready and I have seen its effect in a small numberof cases. Similarly a state of cortical insufficiencyapparently exists in some cases of gas poisoning(Yperite, Pyrodin, Lysocin, &c.).
I am, Sir, yours faithfully,Queen’s Drive, N.4. H. POLLAK.
4. Dale, H. and Laidlaw, P. J. Physiol. 1918, 52, 355.5. J. Pharmacol. 1927-28, 32, 465.6. Selye, H. Klin. W schr. 1938, 17, 666.7. Keller, R. Ibid, 1934, 13, 1041.8. Kaunitz, H. Z. klin. Med. 1938, 134, 224.9. Kaunitz and Selzer, L. Z. ges. exp. Med. 1938, 103, 664.
10. Einhauser, M. Klin. Wschr. 1939, 18, 423.11. MeCance, R. A. Lancet, 1936, 1, 823.
FRACTURED FEMUR IN CONVULSION
THERAPY
SiR,-In the article on fractures of the neck of thefemur in convulsion therapy by Mr. Gissane, Dr.Blair and Mr. Rank in your issue of March 9, I wasparticularly interested in the first of their five con-clusions based on 4 such fractures (the eldest patientbeing aged 41) in a series of 96 cases. " Convulsiontherapy," they say, " should not be used in elderlypatients or in those who have had prolonged periodsof inactivity, because the bones of such people haveatrophied from disuse and readily fracture." I ventureto disagree with that conclusion on several points.
I have now treated over 160 cases with Cardiazoland in these there have been but 2 fractures, 1 ofthem reported elsewhere (Brit. med. J. 1939, 2).Of a recent series of over 80 cases that I have treated,25 fell within the age-group 50-65 years, composed asfollows: 50-55 years, 13 cases; 55-60 years, 8 cases;60-65 years, 4 cases. In only one of these, a womanof 59, did a fracture occur-of the head of the lefthumerus. Most of the 25 cases between 50 and 65had " prolonged periods of inactivity." Indeed, someof them had been practically bed-ridden for years.I think these facts speak for themselves.
I also disagree with two other points in their article-namely, " that the intensity of the muscular con-tractions during these convulsions is the mostimportant factor in the causation of the fractures";and that the fit of cardiazol convulsion and that ofidiopathic epilepsy " differ greatly in the intensity ofthe muscular contractions." From the study of theconvulsions produced in approximately 3000 injections,the aetiology of cardiazol fractures to my mind is notthe intensity of the muscular contractions acting onthe alleged brittleness of bones in the elderly or inthose who have had long periods of inactivity. Thefractures appear to be due in most cases to thetechnique adopted during treatment. Details of theactivities of the doctor and nurses before and whilethe patient is convulsing are usually lacking, but onegathers from reading different papers that such activi-ties are directed towards restraining the movements ofthe patient. This, in my opinion, is a definite mis-take ; the behaviour of the doctor and nurses duringthat period should be one of complete inactivity savefor guarding against dislocation of the jaw. Anymovement of the patient during that period (save thejaw movement) should be quite unrestrained, and it isby acting on that maxim that I believe the number offractures in my series of cases have numbered nomore than 2. The maxim was arrived at by consider-ing the difference in incidence of fractures in cardiazoltherapy and in idiopathic epilepsy. Since I couldsee no difference in the intensity of the muscular con-tractions in the two types of convulsion, I concludedthat fractures in idiopathic epilepsy are rare becausein them there is seldom either opportunity or occasionfor restraint-the convulsion is regarded as a matterof course and the various parts of the body are
allowed to look after themselves, which they seem todo very successfully. This hypothesis was borne outin the lady of 59. Her fracture occurred most prob-ably as the result of restraint exerted on the affectedregion by a nurse who was new to cardiazol treatment.It is perhaps superfluous to recall how a limb in thetonic stage is no longer a limb in the ordinary senseof the term; it loses its flexibility and range of move-ment and becomes a rigid structure unyielding saveto considerable external force. It is easy to see howa fracture can occur when to the muscle strains onthe bone already present external restraint is added.
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I have found cardiazol therapy very safe at all agesand in the most diverse physical states, both abnormaland normal, and I think it would be a pity if someonewere to be prevented from employing it in the elderlyor in those who have been inactive for a long periodby the article referred to. The categorical statementthat in my experience (and I think I have adducedenough facts to support it) age or prolonged inactivitybear no relation to the incidence of fractures may, Ihope, have the necessary corrective effect.
I am, Sir, yours faithfully,RANKINE GOOD,
Assistant Medical Officer, Glasgow Royal Mental Hospital.
CONTROL OF WOUND INFECTION
SIR,-The paper by Mr. Fuller and Major Jameson p. 487 of your last issue has left me with theuneasy feeling that in our enthusiasm for this newpanacea we may forget or neglect older and provedpreventive measures. If Str. pyogenes is to be thegreat enemy of the wounded in this war as it appar-ently was in the last, the surgeon and the medicalorderly should be encouraged to follow the example ofthe obstetrician and the midwife, just as the latterhave for the past decade or two been exhorted toemulate the surgeon. The mask and glove have provedtheir worth in the prevention of streptococcal puer-peral infection in domiciliary practice, and their usetogether with isolation of the septic case has reducedstreptococcal infection to a minimum in well-conductedmaternity institutions. If for domiciliary practice wesubstitute the regimental aid post and the casualtyclearing station, and for maternity institution the basehospital, these methods in conjunction with surgicalprophylaxis should accomplish much in the preventionof streptococcal infection of wounds. At the basehospitals, where the risk of infection is greatest, largewards should be subdivided into smaller units, andthere should be ample isolation accommodation so thatpatients already infected may be nursed separatelyfrom " clean " cases.
Experience teaches that when a ward is overloadedwith infected cases due to one species of micro-organism-e.g., Str. pyogenes-the ordinary precau-tionary measures to prevent the spread of infectionare unavailing, and to put the onus on the nursingstaff is unjustifiable. With an enforced blackout andpoor ventilation air-borne infection becomes increas-ingly important and attention should be directed tomethods for the prevention and cure of infectedatmospheres. A bacteriological control is also essen-tial, the more so as the sulphonamides-if our analogywith puerperal sepsis holds good-may mask but noteliminate the streptococcal invader.
I do not wish to minimise the probably great useful-ness of chemoprophylaxis in streptococcal infectionof wounds, but, as I foresee difficulties in giving theprescribed prophylactic course under field conditions,I feel that the indiscriminate use of these drugs shouldnot displace general preventive measures. Further,the clinician seems to be less enthusiastic about thefree use of sulphonamides than is the laboratoryworker whose mice cannot tell of the depressant andother toxic effects of the drug.As for gas gangrene, it may well be that a com-
bination of surgical, antitoxic and chemical prophy-laxis will be required to deal with this rapidlyprogressive and highly fatal infection.
I am, Sir, yours faithfully,London, N.W.3. R. CRUICKSHANK.
LIPOCAIC
SIR,-In the annotation on lipocaic in your issueof March 2 I was interested to see the statement that
Dragstedt and his collaborators have been able toextract an active preparation from pancreatic glandsin which almost the whole of the acinar tissue haddegenerated as a consequence of ligation of the pan-creatic duct. I have closely followed Dragstedt’swork, but have failed to find a paper in which thisspecific observation-a matter of some practicaldifficulty-has been recorded. I am familiar withthe observation of Dragstedt and his colleagues thatdogs in which the pancreatic duct is tied and inwhich the acinar tissue of the pancreas has largelydegenerated do not die with fatty infiltration of theliver; but this observation does not cover the state-ment that lipocaic has been prepared from suchdegenerated pancreatic tissue.
I am, Sir, yours faithfully,F. G. YOUNG.
National Institute for Medical Research,Hampstead, N.W.3.
*:),* The statement to which Dr. Young has drawnattention has not as yet appeared in print and wasmade during an informal discussion at the meetingof American Physicians held at Atlantic City last
May.-ED. L.
THE PULMONARY CIRCULATION
SiR,-In his interesting article in THE LANCET ofJan. 6, Dr. R. A. Young devotes a paragraph to apredecessor of Servetus, the Arabian scholar andphysician Ibn-an-Nafis. The bibliography there doesnot mention the important contributions to this
subject by Dr. M. Meyerhof of Cairo, who sum-marised a previous work of his in Isis, 1935, 23, 100.Here, on p. 116, will be found a better translationof the important Arabic passage than that quoted byDr. Young, and the same article will also serve toestablish the following points: the book of Ibn-an-Nafis in which he exposes his theory is not a religiouswork but a commentary on the anatomy in the Canonof Avicenna; the author himself was not a heretic butan orthodox Mohammedan scholar; his assertion thathe did not perform dissection must be accepted, andhis practical directions are simply taken over fromGalen; finally, Dr. Meyerhof comes to the conclusionthat Servetus, notwithstanding some astonishing coin-cidences, cannot have been influenced by the work ofIbn-an-Nafis.
I am, Sir, yours faithfully,
London, W.C.I.JOSEPH SCHACHT.
SUGAR IN MEDICINE
SiE,—When the sugar-rationing scheme was
announced recently all those concerned were gratifiedto learn that the position so far as the use of sugarin medicine was concerned remained unaffected. Thispleasing news was, however, accompanied by an
indication that every opportunity should be taken toreduce voluntarily the quantity of sugar for medicalpurposes in order that a substantial contribution mightbe made to the general reduction in sugar usage whichit was necessary to effect. Such a contribution wouldnot only assist in conserving the resources of thecountry but might also avoid a compulsory reductionat a later stage. If compulsion is applied there maywell arise the question of alternative formulae forsugar-containing preparations in the British Pharma-copoeia and the British Pharmaceutical Codex.
