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DR. H. O.

GUNEWARDENE
M.B.,B.S. Lond., D.M.R.E. Cant.
.

December 1942
Hubert Oliver Gunewardene was born in Sri Lanka, then Ceylon, on June 6th. 1890. He was educated at the Colombo Academy, which later became Royal College, studied medicine at the Medical College, Colombo, and did his post graduate work in London, England, where he later had rooms in Harley Street as a Consultant Cardiologist. He later returned to Ceylon to practice.
In about 1933, at the behest of the Government, he returned to England to study radiology to set up and head, in Colombo, Ceylons rst Department of Radiology and X-ray facility.
1

Dr. Gunewardene, second from right, with friends and his son Ian*, on his right, in 1952. *On leaving Sri Lanka in 1969 Ian changed his surname to Gardner.

Mrs. H.O.Gunewardene, fifth from left, her daughter, second from left, her then daughter-in-law, seventh from left, with relatives in England in 1957. 2

POSTED HERE ARE SOME OF DR. GUNEWARDENES PUBLICATIONS ON HEART DISEASE


ET AL

DR. H. O. GUNEWARDENE
M.B.,B.S. Lond., D.M.R.E. Cant. 1890 - 1954

Thirty-five Years Study Of Clinical Heart Disease* Being The unfinished manuscript of a paper written by the late Dr. H.O.Gunewardene, Consultant Cardiologist, Colombo.
*Read by Dr.Stanley de Silva at the 67th.Anniversary Meeting of the Ceylon Medical Association (Section on Medicine) on 15th. November 1954.

This document was posted from May & Baker Ltd., Dagenham, England on 28 June 1966 to Dr Guy de Silva, nephew of Dr. Gunewardene, who handed it over to Dr. Gunewardene's widow who added the notation "Unnished Manuscript".

THE MANUSCRIPT

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-4 JAN. 4; 1936 tEIMABITURN't 87 JAN.~~ ~~~~~~~~~~~~CORl?ESPOND)EN' E .~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~EIA .tNA


96-C
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" The Local Origin of Cancer. The application of these observations, Dr. Gye continues, lies in the fact that almost all the ' cancer cures ' which are produced from time to time are based on the idea that the tumours arise from some constitutional defect in the body of the patient. . . The theories upon which these practices are based are in obvious conflict with the conception of the nature of cancer indicated above. "

As the heading indicates, the section is devoted to stressing the view that the constitutional and local origin theories are opposed and mutually exclusive: " Constitution Avenue Closed." In the next section we read, inter alia: " Professor Kennaway and his collaborators have been able to synthesize chemically pure substances with definite carcinogenic Properties. Some of these stubstances are related chemically to the sterols, which are normal constituents of the body." (Italics mine.) Really, Sir, but for the prominent notice we saw I should have said we were in Constitution Avenue after all. " Normal constituents of the body," " related chemically," " carcinogenic properties ": did I hear someone say " It is Constitution Avenue "? How came we here, then? That side entrance you cannot have noticed, marked " Private, for Laboratory Workers Only ; for Key Apply in Person to Director." Shelley, long ago, wrote: "Nature has gifted Man with all-subduing will; Matter, with all its transitory shapes, Lies subjected and plastic at his feet." Cancer has not quite yielded yet to that all-subduing weapon. There are many whose lot does not permit of whole-time devotion to that end. There are intelligent people among the laity as sincerely interested in the campaign- as the whole-timers. To these classes annual reports are the most authentic sources of information. While no one would claim for them infallibility, yet coming with the imprimatur they do, they are taken as of ex cathedra status, so it is of some importance that they shall be at once intelligible and trustworthy guides to the existing situation. Incompatibles, besides being unpalatable, are unaesthetic. Only when the goal has been reached will it be seen what body of opinion and method of attack has been most nearly on the direct course. Wait and see. Meantime, could the director, be directed to rewrite this reportomitting the sobstuff and the special pleadings but carefully correlating the data-it would be time well spent. Also we may remind ourselves that progress is not necessarily rectilinear as in Euclidean postulate. It may be sinusoidally serpentine, corkscrew, or (even as appears in this case) a kind of zigzag.-I am, etc., London, W.6. Dec. 19th, 1935. W. M. HEWETSON.

space because it should have a place similar to rheumatic carditis in the textbooks now in use in the Tropics, which do not give it the consideration it deserves. I considered it needed a special place in view of the fact that a few years ago there were not, in a country with several hundred practitioners, any more than half a dozen blood pressure instruments, and consequently that hypertension was not recognized as a common cause of cardiac disability.-I am, etc., December 16th, 1935. H. 0. GUNEWARDENE.

Williamson, 1934). High blood pressure was given special

Medico-Legal
DEATH FROM AMIDOPYRINE POISONING A death from amidopyrine poisoning, the second in the course of a few weeks, was the subject of an inquest held by Dr. Bentley Purchase, H.M. Coroner for St. Pancras, on December 13th and 20th. Sir Bernard Spilsbury, who performed the necropsy, said that the deceased was a stout woman of 60 with signs of chronic osteo-arthritis and rheumatism. The heart was enlarged and its cavities all dilated ; the surface showed some petechial haemorrhage. There was also fatty disease of the -heart muscle and brown atrophy. The cause of death as certified was acute bronchopneumonia, the lungs being congested, especially in the lower lobes. The thyroid was rather small, the liver fatty, and there were small haemorrhages in the spleen; the kidneys were enlarged and congested, and the suprarenal glands somewhat enlarged. There was acute inflammation of the tonsils which had spread over the wall of the pharynx, with some membrane on the surface; the entrance to the larynx was oedematous. There was a certain amount of chronic gastritis. The marrow in the femoral shafts was a deep red. The white cell count on admission had been 4,400 cells per c.mm., dropping to 1,000 and rising to 2,000, the figure obtained on the last count before death (four days after admission). No polynuclear cells were seen. There was a history that to relieve her rheumatism the patient had- been in the habit of taking some antirheumatic pills. The coroner adjourned the first hearing in order to allow the chemists who had made the pills to appear if they wished. Accordingly, at the adjourned hearing a representative of the firm gave evidence that the bottle from which the deceased had been taking pills had contained when full forty tablets, the analysis of which was aspirin 21 grains, amidopyrine 1/8 grain, and caffeine 1/8 grain. Not only was the prescription stated on the bottle, but the word " Poison " also appeared, as this would be required under the new Poisons Act next May. The tablets Fjvere packed by a large firm of manufacturing chemists, and were the same as others sold by many retailers. They had sold large quantities for several years and had never before heard of any untoward result. There was no evidence to show the period over which the deceased had taken the pills. Sir Bernard Spilsbury, in explaining the aetiology of agranulocytosis, said that the sensitivity to amidopyrine could hardly be caused in less than six weeks, and usually took over a year to be established. The dosage given on the bottle was two tablets three times a day. Analysis of the organs-would probably have shown no amidopyrine, as the drug was not retained in the body. The coroner said that after the last case he had investigated he had communicated with the Poisons Board and the Home Office. They had shown great interest, and- he understood that provision was being made to put amidopyrine into the same group as the barbiturates, which were controlled without being labelled as poisonous or dangerous. He considered that the chief requirement was not to brand the drug as dangerous, but to check its promiscuous use. On the evidence, he assumed that the deceased was one -of the few persons who were susceptible to the action of amidopyrine. He entirely accepted the evidence of the chemist's representative that

Heart Disease in the Tropics


SIR,-Will you permit me to make a reference to one or two points in the review of my book Heart Disease in the Tropics which appeared in a recent issue of your Journal? The " perhaps unnecessary detail" appeared necessary to me as author because I felt that no detail should be left out in support of an observation that diastolic murmurs which were diagnosed by most competent observers-one of them a gold medallist in medicine in the London M.D.as aortic regurgitation or mitral stenosis disappeared in the course of treatment, a fact in favour of which no modern textbook gives any support. The reference to diabetes was made owing to the very common prevalence of high grades of glycosuria in men and women in Ceylon, and in keeping with my concurrence with the author in his view contained in the best book on the heart I have read in recent years: " Toxic blood states such as occur in diabetes and nephritis must act deleteriously on the myocardium and vessels " (Vital Cdrdiology, by Bruce

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OCT. 13, 1934]

CORRESPONDENCE

THE BRITTSH L[MEDICAL JOURNA

699

SIR,-In your issue of August 25th " M.S., F.R.C.S." appears to call for a review of the vast amount of work Publicity written on high blood pressure. The cases to which he SIR,-From time to time you publish in your corre- makes reference appear to cast a cynical doubt on the spondence columns and elsewhere indignant protests from now recognized fact that, as a rule, high blood pressure practitioners whose articles have been quoted by the lay certainly carries with it a risk which, to our shame it press, and who wish to repudiate any responsibility for must be admitted, has been seriously overlooked since their appearance. I wonder if there is any advantage in Clifford Allbutt drew attention to this disorder. The such disclaimers., Those who are familiar with the profes- condition, according to Fahr, claims 10,000,000 afflicted sional status of their colleagues require no such assurance. in America, and 200,000 deaths a year-an incidence as Others acquainted with the methods of journalism are common as cancer and tuberculosis together according perfectly well aware that no precautions can prevent to Parkinson it is a " very common disease, which is these occurrences. And a tiny minority who might be responsible for so much suffering and mortality in late willing to accuse your correspondents of seeking publicity middle life and early old age." I can endorse Parkinson's or notoriety may even interpret the disclaimer as cor- observations even more strongly from my experience in roboration of the original intention! In any case nothing this country, where the ravages of rheumatic fever are can prevent the lay journals from quoting from your not so prevalent as in the West, and therefore show up columns, extracting the relatively dramatic, and un- hypertensive failures more readily. One is tempted to ask: Has " M.S., F.R.C.S." met no happily, on occasion, misquoting and misrepresenting. For the author of the original article to protest is other cases of high blood pressure? If he has not he is an extremely lucky medical man. If he has met many obviously useless. Is it too much to say that not oniy cases with such high diastolic pressures, surely there must is it useless but it is quite unnecessary? There is another aspect of this subject to which refer- have been many with serious complications. I have had ence may not be inappropriate. The interests of medical several friends and many patients with diastolic pressures men are not by any means restricted to their professional of 170; very few indeed are alive. I have seen four life, and there are certain, outside activities upon which cases which had systolic pressures of over 300. These they are, rightly or wrongly, 'regarded as authorities, and could not be recorded, as the manometer only read up to upon which their opinion is considered to be correspond- this figure. The diastolic pressures in them were over 160. ingly desirable. From their familiar-association with the All these patients were over 60 years of age, and until use of the telephone doctors are particularly fair game a short time prior to a fatal issue had nothing more than for attack through this convenient but highly dangerous the mildest general symptoms. One patient of mine, 68 medium. And once your ear is at the instrument and years old, apparently in good health, had a systolic your arrival admitted, and you are inveigled into saying pressure of 210 and a diastolic of 95; another, a lady, something, no matter what, the mischief is done. If, a systolic of 300 and a diastolic of 90. These striking good-naturedly, you believe you may be doing a service exceptions, and many more like them, have not made me to the public-and that really is the motive on most ceaseu to believe that high blood pressure, particularly occasions-publicity is inevritable. The most fervent when it occurs under 50 years of age and once any request to withhold your name is unlikely to be respected, symptoms are manifested, is a danger to life of which since any news value attaching to the opinion of one some kind of notice should be taken. who is being represented to be an authority depenids An account of the numerous strokes which appear in entirely upon his name being mentioned. Alternatively, these cases is given in my Sir Charles Hastings prize essay a curt refusal' may rebound upon you'to your subsequent on "The Stroke in High Blood Pressure," published in discomfiture, and those who have once suffered in this the British Medical Journal of January 30th, 1932. way have learnt that it pays to be courteous. I am, etc., At midnight a few weeks ago the news editor of one of H. 0. GUNEWARDENE. General Hospital, Colombo, the daily papers felt unable to rest until he had telephoned Ceylon, Sept. 22nd. to take my opinion upon a " story " just to hand from South Africa: an indignant protest against holding Olympic Games for women because there was abundant Preliminary Ligature in Toxic Goitre evidence that some men had actually competed. It says SIR,-The correspondence concerning preliminary ligasomething for my forbearance that my only observation, even at this hour, was that I knew absolutely nothing ture in toxic goitre has probably contLnued long enough about it. Yet this became ingeniously interpreted as an for adequate ventilation of the different opinions that authoritative denial of the rumour. A week later-again are held. An excellent summary of the position was at the (apparently critical) hour of midnight-I was supplied in your issue of September 29th by Sir W. I. approached by another journal in reference to an inquest de Courcy Wheeler. I cannot, however, remain silent in that had been held that afternoon, at which the coroner view of the repetition by Mr. G. Bankoff in your last had expressed his opinion that the suicide of some issue of the astonishing and dangerous fallacy that the unhappy young man was due to his " having lived too degree of the reaction depends, not on the amount of thyroid tissue that is removed, but on how much is left strenuously.-" " Did I think the coroner was right?' beh:nd. If this were true, the only logical inference would and " What did I suppose the coroner meant? " It may be that some of us might succeed in fencing be that the lowest mortality rate would be obtained by ourselves round by a complete secretarial inaccessibility performing a total thyroidectomy in all the worst cases. (more appropriaxte, perhaps, to a Pope than to a medical This is contrary to clinical experience, and the principle man), and thus receive adequate protection from tele- would be most dangerous if generally applied. I fully phonic assault. But by the time we had acquired an agree with Mr. Hawe and Mr. Bankoff that " for the eminence commensurate with such a state we should be good success of the operation it is imperative to remove at least three-quarters of the gland," and in fact I fre" in the news " anyway.-I am, etc., quently remove more than this. In the great majority of patients it can be done in one operation, but in a London, WV., Oct. 8th. ADOLPHE ABRAHAMS.

CORRESPONDENCE

Is High Blood Pressure a Risk?

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JAN. 30,

1 9321

THE STROKE IN HIGH ARTERIAL -PRESSURE

r THEBRITISH L MEDICAL JOURNAL

181

lesions have developed, the patient has already ceased or forgotten to look upon the earlier symptoms as part cf the same disease in its undeveloped state. High blood pressure, whatever its etiology, is common enough in general practice. No one is in a better position to study those aspects of it which throw light on its causation, and on some of the features which forecast the final doom, than the family practitioner. Methods of investigation are no doubt limited, but the mass of clinical material is heavy. No apology is made for not resorting to those special tests which can be carried out only in a fully equipped laboratory with a full staff, for the purpose of this essay is to record the clinical observations made on the so-called " stroke " as it occurs in high arterial pressure.

plegic; (3) localized-for example, tongue; and (4) diffuse. The last variety usually occurs as a terminal event, being due to a severe haemorrhage which causes sudden death, or to one which produces paralysis, first of one side of the body and then of the other. According to their duration, we may say that they are: (1) permanent, (2) present for a few days or weeks, and (3) transient. The annexed diagram gives a clear picture of what may occur on the motor side. StRO/E
PQtMOR
f

SW

SoR

DEFINITION OF "STROKE A stroke is defined in Dorland's Medical Dictionary as a sudden severe attack, as of apoplexy or paralysis." Saville considers " stroke " to be synonymous with apoplexy, for he defines each word as " a term which may be conveniently retained to indicate a sudden unconsciousness due to a vascular lesion within the skull." I propose to resort to a certain degree of licence in the use of the word, interpreting it as a " sudden severe attack," not necessarily apoplectic, and thus implying that these attacks are not confined only to the motor side. There appears to be somb justification for such a departure, for one finds Batty Shaw saying (under the heading " Persistent or temporary hyperpiesic paralysis "): " Sometimes the paralysis affects the sensory instead of motor areas, so that the patient becomes blinded without any changes being discovered in the retina or the brain." A little elasticity in my definition seems justified, not only because it helps to explain more fully the various forms these attacks take, particularly in the earlier stages of high blood pressure, but also because it helps to give a mental picture of the much-neglected sensory forms.
FREQUENCY OF STROKE Stroke occurs so commonly in high pressure, at least in Ceylon, that the scant references to it in standard textbooks is surprising. Theodore Thomson in Price's Textbook of Medicine says, " sometimes transient paralysis occurs," without any mention of the sensory attacks. Batty Shaw makes the statement quoted above in a superficial but none too impressive way. East and Bain, in Recent Advances in Cardiology, make no reference to the sensory stroke. In what they call the second stage, they say, " symptoms will rarely be experienced which refer to the pressure," also stating that the clinical features " are strikingly few "-this is in contrast to my finding th'at the strokes, all except the apoplectic, are most common at this stage. Vaquez, on the other hand, states clearly: " Transient aphasia and fleeting paresis, specially brachial monoplegia, are frequent incidents in vascular hypertension. They appear and disappear suddenly, leaving no traces, and may occur several months later." He lays some stress on the mental symptoms (uncommon in my series), which, he maintains, assume the most varied forms-for example, amnesia, mental confusion, and suicidal tendency.
MOTOR AND SENSORY STROKES Defining " the stroke" as a sudden severe attack drawing the attention of the subject of hypertension to a change in his normal motor or sensory phenomena, one can classify " motor strokes " under the main heads of the paralytic and the paretic. These can be described according to distribution as: (1) hemiplegic; (2) mono-

^tJ

PER,IANiNF1W/N

O>R

ffwD4Ys OR wEiea

Dysarthria or aphasia.

On the sensory side we get similar changes: complete loss of sensation, as in coma, and changes in sensationnamed " incomplete " for the purpose of the diagramthese being analogous to the paralytic and the paretic forms on the motor side. The distribution and duration are similar to those occurring in the motor phenomena. The diffuse form, including cases in which tingling or numbness, or " a peculiar feeling all over the head and body," has been reported, is rare. Changes in sensation have been variously described by the patients themselves, and may occur associated. with, in the absence of, or following motor phenomena. Tingling and numbness are

(coi'm)

MAthsrIs,.5 rTAWL/AV, AVWNESSs INa L/NO1SS)

described as irritating " the peculiar dry feeling of the limb, as though it had been immersed in formalin and taken out "; again, " When warm water is taken I feel it hotter on one side of the tongue; and, further, on shaving I do not feel the razor well on the recently affected side." In another case a patient complained of nurnbness of the ear, left upper limb, and distal part of the left leg after motor power had returned His description was: " as though I have placed my hand on a lump of ice and removed it." Of the ear he said: " When I j scratch my ear it feels plain.'

common. One patient of mine described the sensation as " a cotton-woolly feeling-the face feels heavy o-fi that side." A doctor, in whom a monoplegia had disappeared,

24

182 JAN. 30, 1932]

THE STROKE IN HIGH ARTERIAL PRESSURE

r M THE BRITISH
IEDICAL

JOURNAL

DIASTOLIC PRESSURE IN STROKE It is interesting to study very clearly at what stages in high arterial pressure the stroke supervenes. In my series of cases the stroke, sensory or motor, has not appeared in a single instance in which the diastolic blood pressure was under 1 15. In 20 per cent. of the cases the stroke-in most transient, in a few permanent, in one fatal-occurred with a diastolic blood pressure between 115 and 120. In ten out of the 150 cases death resulted from what appeared clinically to be definite cerebral haemorrhage; in nine of these, the patients were actively or restrictedly pursuing their usual occupations. Again, in nine of these ten the diastolic blood pressure was over 135, the systolic being 200 and over. In 10 per cent. of the series the transient and permanent strokes occurred in cases with a diastolic blood pressure of over 125. It seems, therefore, that sudden changes in the normal sensory and motor phenomena appear most commonly with a diastolic blood pressure between 115 and 125, and are altogether absent in cases with diastolic blood pressures under 115. Cerebral haemorrhage seems to be uncommon in patients under observation, and they are warned against any but a very quiet life. Fatal haemorrhage seems to ensue mostly in patients who carry on ordinary occupations without making allowances for their abnormal pressure. Indeed, it seems that the catastrophe of fatal haemorrhage is the one phase of high arterial pressure in which the practitioner or specialist can give little relief. There is therefore all the more urgent need to study the earlier signs and symptoms very fully, for then therapeutic measures can be resorted to in time, and where these are likely to be of no avail, relatives and dependants may be warned of the possibilities ahead, and adjustments relating to business, finance, or family matters may be made.
HEART FAILURE AND STROKF, The relation of the stroke to heart failure consequent on high arterial pressure is worth studying. My observations seem to suggest that fatal cerebral haemorrhage, or even transient strokes, are very uncommon once failure has set in or the heart has begun to show considerable enlargement, with dyspnoea and other symptoms of a tiring cardiac musculature-even though at this stage it is observed that the blood pressure, systolic and diastolic, remains high. In three cases of mine, however, there was very marked enlargement of the heart with the apex in the sixth- space- and anterior axillary line, with thickened vessels and a locomotor pulse (brachial), but with practically no symptoms referable to the heart. These three patients are reported to have died of cerebral haemorrhage. The impression is gained, in a review of my cases, that patients with hyperpiesis, showing few or no symptoms referable to the heart, with or without cardiac enlargement, are particularly prone to die of cerebral haemorrhage.
DIAGNOSIS AND PROGNOSIS In this country (Ceylon) there is a popular belief that the native doctor, so called because he practises Ayurvedic medicine, excels the practitioner of Western medicine in the diagnosis and treatment of paralysis. This is no doubt due, in my opinion, to our mistakes in the matter of prognosis in these cases, and to our failure to appreciate the transient nature of the attacks. A common procedure is as follows. A man gets hemiplegia. The nearest practitioner is sent for; he diagnoses cerebral haemorrhage and gives a gloomy prognosis, hinting at the possibility or probability of death within twenty-four hours. The blood pressure is not taken.

In despair the relatives run to the native doctor, to whom no circumstances are hopeless, and who not only promises relief, but paints the picture of a permanent cure. The case falls into the hands of the latter, and time, with the other, restricted diet on the one hand and rest works the miracle. In one case the patient gives this " Dr. X saw me, and said it was a ' spasmodic ' version: stroke. We took native treatment, as Dr. X said recovery would take three months, and it was due to high pressure." If the possibility of recovery in a few hours or days had been mentioned with confidence the practitioner would have retained his patient as well as his fees. In sensory cases the phenomena are generally classed under neurasthenia, neuritis, and hysteria, and the possibility of pressure as a causative factor is missed. Thus in this country, and elsewhere too, misdiagnosis must be
on

common.

disease, and so to correct or amplify the present findings. From the point of view of the practitioner there is everything to gain and nothing to lose by agreeing with Cabot that " the measurement of blood pressure is the most important of all the recourses that have been added to our armamentarium in the last fifteen years." When the frequent occurrence of sudden motor and sensory changes as a result of high arterial pressure is more widely recognized, the diagnosis and prognosis will be placed on more reliable data.

view-namely, to invite the study of this

These observations have been made with

one

object in
common

CONCLUSIONS AND SUMMARY the stroke In a final review of these observations in high arterial pressure, one appears entitled to infer: 1. That transient or permanent paralyses of varied distribution occur fairly frequently. 2. That the hitherto neglected sensory phenomena have a distribution similar to the motor phenomena; that they also occur frequently, and are probably caused througb an affection of the sensory areas, the pathogenesis being similar to that in the motor cases. 3. That strokes often attributed to other factors, such as shock, exertion, and emotion, are the result of an already existing pressure exacerbated by the influence of these factors. 4. That cerebral haemorrhage does not seem to occur with diastolic blood pressures of under 115 (whatever may be the systolic), and that prognosis may be based on this observation. 5. That cerebral haemorrhage occurs most commonly in people working in defiance of an already existing pressure, and without taking any account of this abnormality. 6. That any kind of paresis or paralysis is very rare in cases in which the diastolic blood pressure is under 115. If they do occur, the minimum diastolic pressure is over 115 at the time of the stroke. Strokes at this pressure are rarely fatal or permanent. The former occurs in patients with thickened vessels or other disease ; the latter in an unfortunate few, or in those in whom the causative factor is other than hypertension. 7. That cerebral haemorrhage seems to occur more frequently in those cases of hypertension which show neither marked cardiac enlargement nor symptoms, and rarely in those cases in which there are signs both of considerable cardiac enlargement and symptoms of heart
on

failure.

I am grateful to my medical colleagues at the General Hospital, Colombo, for givinlg me opportunities for verifying my observations with cases inl their wards.

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111

DEC. ~~~~~~~~~~~~~~~~~~~~~~ ACASE OF ADDISON'S DISEASE D EC. 16, 1933]

After the administration of eucortone, 5 c.cm. intravenously, and 50 grams of dextrose by mouth half-hourly estimations of blood sugar yielded the following results, 117, 113, 94, 68, and 78. Blood pressure readings taken at ten-minute intervals after an injection of eucortone showed no rise of blood pressure. Progress of Case From February 6th till March 15th, inclusive, the patient received 5 c.cm. eucortone intravenously each day, with the exception of the ninety-six hours above-mentioned. Under this treatment he remained free of most of his symptoms, e;uch as vomiting, insomnia, anorexia; but there was only a gain of 2 lb. in weight. There was but slight lessening of pigmentation, and the blood pressure varied between 70/50 and 78/50. On March 1st three horizontal lineae atrophicae had appeared on either side of the spine opposite the eighth and ninth dorsal spinous processes. Lines of lighter colour, like those already mentioned above, had appeared, two on each' side, symmetrically placed along the pectoral margin of the axilla, and one running from the sternal notch towards the umbilicus. On March 16th whole-gland suprarenal (Armour) was substituted for the eucortone ; three tablets, each of 2 grains dried gland (= 10 grains fresh gland), were given by mouth thrice daily. Within two days the patient expressed himself as feeling much better and stronger than he had done for many weeks. In the following ten days he gained 3 lb. in weight and the blood pressure rose to 90/55. On March 31st whole-gland suprarenal was replaced by a special extract of cortex prepared by Allen and Hanburys for oral administration. It was given in doses as suggested, but the gland equivalent was unknown to me at the time. Within twenty-four hours the lad said he did not feel so well, his appetite began to fail, there was immediate loss of weight, and the blood pressure fell to 78/48. It was then found that this liquid extract, which was being given in doses of half ail .ounce thrice daily by mouth, only contained 1 gram of cortex per 3 c.cm. It also contained 0.05 per cent. adrenaline. A return to whole gland by mouth was made on April 5th, with immediate benefit; all previous symptoms disappeared, the blood pressure rose to 88/58 in forty-eight hours, weight increased, and appetite was excellent. During the ensuing two weeks improvement was rapid; he was able to walk several miles, muscular power was good to exercises directed to correct the kyphosis he responded well. The pigmentation was diminishing very considerably, and the blood pressure remained higher than previously. The pulse sounds noted during sphygmomanometrical readings appeared almost normal. About the middle of April it was noticed that the breasts were enlarged, resembling those of a girl a year before puberty, but without changes in the nipples. During fortyeight hours, April 18th to 20th, treatment was discontinued, with no obvious ill effect. On April 21st cortin organon, 5 c.cm. by mouth, was given. By the evening of that day symptoms of suprarenal insufficiency developed. These had not been noticed during the previous two days, when treatment had been withheld. After

shadows which suggested old calcified tuberculous gland at the root of the lung, but there was no evidence of any changes in the suprarenal glands. A Mantoux test gave a marked positive reaction with vesiculation, followed by induration, which persisted for several weeks in dilution 1 in 10,000; with dilutions 1 in 100,000 and 1 in 1,000,000 the results were negative. There was a marked general reaction, the temperature rose to 103.80 F. and the pulse to 112 per minute, with headache, recovery being only completed on the fifth day. There were no symptomns pointing to a focal reaction. Laboratory investigations showed: red cells per c.mm., 6,010,000; haemoglobin, 94 per cent.; colour index, 0.78 ; white cells per c.mm., 6,800. Differential count gave: polymorphonuclears, 43.2 per cent. ; lymphocytes, 51.2 per cent. ; and eosinophils, 5.6 per cent. Meinicke reaction negative. Blood urea 40 mg. per cent. Urine normal. Blood sugar fasting, and twenty-four hours after an injection of eucortone, 72 mg. per cent. ; after 50 grams dextrose halfhourly readings gave the figures 109, 83, 72, and 80. On another occasion, ninety-six hours after the last injection of eucortone, the blood sugar was 80 mg. per cent. ; the boy felt weak and fainted. The blood pressure was 78/50.

three days on 5 c.cm. by mouth, 5 c.cm. were given twice daily intramuscularly, with some improvement. Cortin is preparation of suprarenal cortex made at Oss in Holland by N. V. Organon, who very kindly sent me a supply for a trial at the instance of Dr. Alison Macbeth: 1 c.cm. represents 50 grams of fresh gland. The dose advised-namely, 5 c.cm., intravenously-for maintenance is doubtless about correct, and corresponds fairly closely, to that of eucortone. A second return was made to dried whole gland, and the patient took his discharge from hospital on May 4th, 1933, with a supply of tablets. He came up once two weeks later for more tablets, and then disappeared; all efforts to trace him failed. On July 1st, 1933, he returned in a condition of collapse, with all his previous symptoms returned. Weight, 119 lb.; temperature, 980 to 990 F.; pulse 72/84; blood There were present extreme asthenia, pressure, 60/36. negativism, nausea, vomiting, and abdominal pain. During the first week, 10 c.cm. eucortone was given daily; later an oral preparation of eucortone, made by Allen and Hanburys, was tried, and the addition of adrenaline subcutaneously was made. The patient continued to lose weight, and it was impossible to get him to take nourishment. A return was made to intravenous eucortone, kindly provided by Allen and Hanburys: 10 c.cm. were given twice on the first day (July 22nd) and the second day, then 10 and 5 c.cm., and thereafter 5 and 5 c.cm. each day. There was some response in that a little nourishment was taken and the extreme sense of weakness was less marked; the blood pressure remained at 60/36. Eucortone was then discontinued, as the supply had come to an end. Twenty-four hours later the patient collapsed, became comatose, and died. Necropsy was refused.
REFERENCES

MEDICAL JOURNAL rm~~~~~~~~~~~~~~

Simpson, Levy: Quart. Journ. Med., 1932, xxv, 99. von dem Borne, G. A. K.: Nederl. Tijdschr. v. Geneesk., 1933, lxxvii, 4, ). 433. Britton, Harrop, and Weinstein: Journ. Amer. Med. Assoc., 1932, xcviii, 1525. 'Swingle, W. W., and Pfiffner, J. J.: Medicine, 1932, xi, 371. Cecil, H. L.: Amer. journ. Physiol., 1933, c, 463. 6 Rowntree, Greene, Ball, and Swingle: Journ. Anmer. Med. Assoc., 1931, xcvii, 1446.
2

TREATMENT AND CONTROL OF ESSENTIAL HYPERTENSION


A NEW THERAPEUTIC MEASURE
BY

H. 0. GUNEWARDENE, M.B., B.S.LoND.,


D.M.R.E.CANTAB
LATE

CLINICAL

ASSISTANT, NATIONAL HOSPITAL FOR DISEASES


OF THE HEART, LONDON

In 1917 Cyriaxl reported good results in cases of moderately high blood pressure obtained by what he described as " mobilization of the spinal column," by which he meant active and passive movements of the vertebral joints, and passive manipulations, vibrations, petrissage, etc., of the erector spinae muscles. His explanation of raised, pressure was, apparently, that congestion of these parts led to irritative states of the erector spinae, setting up a series of sensory stimuli to the posterior spinal nerves, which in turn gave rise to a series of pressor effects. Whatever the -explanation, his figures seemed to show a definite diminution of the blood pressure in his pat:ents. Although unwilling to accept the theory on which the treatment was based, I ventured to modify his method by substituting electrical stimulation of the skeletal muscles, and submitting patients with high grades of pressure to treatment on these lines. As a preliminary the patients were tested to see what effect the resulting muscular contractions had on the pulse rate, particularly as some of them were on the verge of cardiac failure, a few actually exhibiting oedema of the ankles and a more than moderate enlargement of the heart. In every case the pulse rate dropped, sometimes by eight beats to the minute; in a

26

DEc.. 16, 1933]

ESSENTIAL HYPERTE2NSION

MTHABJITISRA

1115

few it ramained stationary in none did it rise. It was argued, therefore, that the method of treatment, instead of throwing a burden on the heart, actually relieved it, and the treatment was carried out with greater zest.
CLINICAL MATERIAL Case 1.-A woman, aged 58, and unmarried, complained her left leg had suddenly become stiff, and that her ,;that had become bad two years previously. Family speech histry:fater ad died f "strke at he ge f 62; history: father had ded of "stroke" at the age of 6 ; he was paralysed for two months; mother had died of bronchitis at the age of 40w ; one brother had died of nephritis, while twvo were well - one sister had high blood p pressure, one had -died of stroke, six were well. Prevlous history: none of any significance; patient 'was fat two years ago. Habits: no alcohol, no smoking; exercise, housework. Condition before- treatment:. the patient was thin, had left-sided hemiparesis, with dysarthria ; she could not get into her car, and walked very slowly. Heart: left border one inch outside- mid-clavicular line,- first sound +, aortic second sound + +. Lungs: nil. Blood pressure 240/140. Urine: specific gravity 1014 no albumin or sugar. After treatment the blood pressure readings were as follows:
Date

on interrogation, breathlessness and pain over the lower part of the sternum following exertion (of two years' durationl). Family history: father died of enlarged liver at the age of 48; mother died suddenly of " debility "; of six brothers, one had kidney disease, two were dead-one dying of typhoid. Previous history: none of any significance. Habits: a little alcohol occasionally, but no tobacco; exercise, a little walking; food, three good meals a day. Condition before treatment: Tightness under the sternum, bad alpiltationl, dyspnoea on Pulse regular, and of teeth ; bowels constipated. exertion,90, slight giddiness ; high tension. Heart: apex beat in the sixth space, anterior axillary line. VesseIs,: palpable. Blood pressure 260/160. Urn Urine: no alui. Lnsni. no albumin. Lungs: nil. On May 25th the blood pressure had fallen to 218/142, and the patient said he felt better. The following were the

blood pressure readings:

Blood Pressure

Date May 18th, 1932


May 25th,

Systolic

Diastolic

Renwrks

260
218
210

Systolic
... ...

Diastolic
140 136
13) 133

,, May 28th, ,,

160 142
120 No pain under the sternum; heart smaller

September 12th, 1932 16th, ,, 21st, ,, ,, 27th, ,, ,,

...
... ...

240 200

... 21st, 184 180 ...

122
122

June 1st. June 3rd, ,, , June 6th, ,, June 17th, ,,


June 22nd, ,,

192

120

190
-

122
-

fingerLeft border of heartline breadth outside nipp)le Left border of heart just outside line Left border of heart in nipple line

~~~~~~~~~~~~~~~~~~~~nipple

30th,
October Eth, ,,
...

,
...

230
175

...

120 - 200

Aug. 16th, ,,

182

180
-

118 115
-

120

Aug. 19th, ,,

Left border of heart in nipple line; no pain under sterntum

Patient ceased attendance

The patient states that she can now get into the car alone, "feels lighter," and walks better. -The left border of the heart is just outside the mid-clavicular line, with a heaving apex beat and an accentuated aortic second sound. Case 2.-A woman, aged 56, unmarried,' complained of a swaying feeling in the head " of s-ix months' duration. Family history: as for Case 1. Previous history: none of any significance. Habits: no -exercise ; no tobacco or alcohol. Heart: left border just outside mid-clavicular line ; aortic second sound +. Lungs: nil. Urine: specific gravity 1012 ; no albumin or sugar. Blood pressure readings were as follows:
-______________________ ___________ Date
...
...

September 12th, 1932


,,16th, ,, 21st, ,,

Systolic Diastolic -_________ _______________________


210

128

...
...

...
...

23rd,

170 158 I 160 178

110 105 105 108


98
112

27th,

...

... 148 (Exercise started)


...

September'30th, 1932
October Eth, 1932
...

...
...

...

170 155

106

On October 8th, 1932, the' left border of the heart was in- the mid-clavicular line; the patient stated that she felt quite well, and had no swaying feeling in the head. In neither of these cases was rest enjoined or medicine given, and there was no restriction of dliet. In both there was marked diminution of the size of the heart, disappearance of symptoms, a considerable fall in the pressure, and obvious general improvement. But one of the patients, the youngern, seemed to have improved more than the elder, .who appeared, wchen she first came to me, to have reconciled herself to a condition of inactivity engenldered by a fear of fatal apoplexy. Case 3.-A clerk, aged 49, married, with seven children, when seen on May 18th, 1932, complained of weakness, and,

Case 4.-A carpenter, aged 60, married, with nine children, was admitted to hospital on June 17th, 1932,' complaining of loss of power of the right limb; he had had a similar attack three years before.' Family history: father died, aged 60 (? boil in chetk) ;. mother died, aged 83, 'of old age. Previous history: malaria, nothing else of significance. Habits: a little alcohol occasionally, but no tobacco; exercise, his work; food, formerly two good meals a day. Condition before treatment: Slight paresis of left side of face, speech slurring. Pulse 90 ; rhythm regular, high tension. Vessels: thick. Heart: left border half an inch outside the nipple line ; aortic second sound accentuated. Blood pressure 210/110. Urine: a trace of albumin, no casts. Lungs: nil. Wassermann reaction negative. Nervous system: knee-jerks and biceps response normal on the left side. July 4th, 1932: Babinski's reflex positive on right side no sensory phenomena. After daily treatment blood pressure 'is 132/92. The patient's speech is normal, and power of the lower limbs has returned ; the left border of the heart is internal to the nipple line. Case 5.-Hotel manager, aged 56, married, with ten children, was admitted on April 3rd, 1932. He complained of breathlessness and palpitation, and occasional swelling of' the legs. Family history: father died of old age at 72; mother died of heart trouble at 68 ; five brothers, all well; four sisters-one dead, the remainder well. Previous history: was in the police force, 1895-1918 ; admitted to hospital four times, once with diabetes; had had malaria in 1892. Habits: a fair quantity of alcohol, but no tobacco; nO exercise now. Condition before treatment: Fat and short-necked type had palpitation and shortness of breath, while teeth were slightly infected ; legs were swollen. Pulse 40, regular. Heart: three-quarters of an inch outside the nipple line, aortic second sound accentuated. Blood pressure 180 / 120. Lungs: nil. Urine: a trace of albumin, but no0 casts. On July 29th the blood pressure was still 180 / 120, but there was no swelling of the legs; the heart was as before; pulse 84 * no oedema. Patient complained of headache about L 1 30 a.m. Renal involvrement was feared, and a urea concentration test was done on August 2n-l (blooXd urea 27 mg. per 100 c.cm.). Concentration before test 1.3 per cent. ; after 'one hour 2.5 per cent. ; after two hours 2.0 per cent. ; after

27

ii o16 DEC. 16, 1933]

moo,

ESSENTIAL HYPERTENSION

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~THE ERrTTSWI I MEDICAL JOURNAL

three hours 2.0 per cent. The treatment was continued, and the following were the subsequent blood pressure readings:
Date
Systolic 162 170

Diastolic

Remarks
Patient felt much better; no headache; no swelling of the feet Left border of heart in the nipple

August 8th ...


August 13th ...

100
106
_

August 18th

...

line. Patient felt much better Left border of heart in the nipple line

In this case the failure to respond to treatment in the early stages suggested renal involvement and impaired renal function, but the blood urea and the urea concentration test gave figures which indicated efficient functioning. Therefore the treatment was continued until the diastolic pressure fell to 100, and the patient felt very much better. Case 6.-Hotel manager, aged 41, married, with two children. He complained of occasional throbbing in the head. Family history: father died at the age of 54 years, and mother at the age of 66; two brothers and five sisters, all well. Previous history: patient consulted a doctor about four years previously for " feeling dizzy suddenly," and one year previously had complained of headache; no history of any other illnesses. Habits: alcohol formerly, but little now ; exercise, only walking associated with work ; tobacco, fifteen cigarettes a day; food, had eaten well previously. Condition before treatment: Headache occasionally, dyspnoea slight; nothing else of significance. Pulse: 85, regular, good volume and tone. Heart: left border in nipple line, second aortic sound accentuated. Urine: specific gravity 1011, a trace of albumin. Blood pressure 220/150. Three weeks of treatment made no reduction in his blood pressure. Renal involvement was suspected, and the urea concentration test was done ; the concentration in the second hour specimen was 1.7 per cent. Treatment was discontinued, but the patient " felt very much better."

The patients whose records are given above received no special medicine, nor was absolute rest ordered for any of them. Cases 4 and 5 happened to be in hospital; the others came for treatment from home. The diet was restricted in all of them. DIscusSION Prior to adopting this method of treatment I had tried diathermy in a large number of cases of hypertension. I was never able to convince myself that pressure was reduced to an extent which could not be explained by the simultaneously ordered rest, in spite of Clifford Allbutt's2 statement nine years ago that " d'arsonvalizatiou by the auto-condensation method is the most valuable immediate aid we possess for hyperpiesia." But it was always strikingly evident that this treatment made the patients feel better, particularly wh en the kidneys appeared to be involved. They nearly always stated they were much better. With the diathermy I often combined radiant heat, particularly in renal cases. The striking reduction of pressure obtained in non-renal cases in the above series would therefore appear to be due to the mobilization of the muscles in the manner described. The results recorded above indicate: 1. IThat in some cases of hyperpiesia the blood pressure drops to low limits, even to normal figures, without rest or medicinal aid ; there is also relief from distressing symptoms. 2. That in other cases the patients are relieved of their symptoms and proclaim that they feel better, but that pressures will not fall. These cases show impaired renal func-

All the patients were treated in hospital. The machine used was the ordinary pantostat-the faradic currentwith a Lewis Jones interrupter in-circui toprevent irregular contractions and uneven, unpleasant shocks. Ordinary batteries have not so far been used, but there is no reason why any method of stimulation should not answer, so long as sudden shocks and irregular contractions are avoided. The Smart-Bristowe coil ought to prove useful. In the absence of electricity, massage would, I imagine, answer; but I am not in a position to vouch for good results. When pressures drop low as a result of treatment-namely, below a diastolic pressure of 110-the patients are taught exercises with which the muscles may be kept in action-particularly the trunk muscles-or advice is given that mild exercises may be resorted to. The patient should be carefully watched, particularly when cardiac enlargement and symptoms are present, or the doctor may one day be called upon to face a charge of " electrocution " when death due to heart failure is attributed to electrical shock. I have deliberately refrained from using subsidiary measures in order to establish the efficacy of this method of treatment, but I am of the belief that therapeutic doses of the drugs ordinarily used (not patent medicines) would prove very useful in maintaining the good results obtained, particularly in those cases in which the blood pressures have not fallen too near normal limits. To establish that the combined measures will give more satisfactory results than those already obtained must remain part of the programme of the future. So widely is it accepted that arterial hypertension, when it throws its strain on the myocardium, takes the patient gradually to hypertrophy, dilatation, and failure, that we find East and Bain in Recent Advances in Cardiology describing " the third stage " of high blood pressure, as much as to imply that the changes are irrevocable. They probably are, but only when the vessel changes have taken place. If such changes have not taken place it would appear from these observations that' extreme grades of enlargement can be reduced to moderate grades, and moderate grades to slight ones. It is now sixteen years since Cyriax published his paper, but the methods of treatment which might have been ceveloped from his findings are still not in vogue. This method of treatment was referred to briefly by me at the discussion on essential hypertension at the Annual Meeting of the British Medical Association in Dublin. I have to acknowledge here my gratefulness to Miss Bevan, sister-in-charge of the electrotherapeutic department, General Hospital, Colombo, for the pains she has taken in connexion

patients.

wvith these cases, and mny indebtedness to my colleagues of that institution for helping me to carry out this treatment on their
1 Cyriax, E. F.: Practitionier, 1917, xcix, 468. 2Allbutt, Sir Clifford: Arteriosclerosis, 1925, p. 91.
REFERENCES

MEDICAL, SURGICAL, OBSTETRICAL


PRIMARY BRONCHIAL CARCINOMA WITH SECONDARY VERTEBRAL DEPOSITS This case is of interest because symptoms were due to spinal cord compression, and the nature of the primary growth remained unsuspected till necropsy was performed.
A labourer, aged 50, on May 10th, 1933, noticed pains in both shoulders and in his back, which came on suddenly and forced him to leave his work; he said he was not subject to backache or rheumatism: 1)uring the next few days the pains were less troublesome, but on May 13th he became constipated, and medicine afforded him little relief. At the same time he noticed that his urine was cloudy. On May 30th he complained of weakness and numbness of his lower limbs, the right leg becoming slightly weaker than the left. The next day he was unable to pass water, and was admitted to the medical ward of this hospital. On examination he was found to be a well-developed man, of good colour, with no signs of muscular wasting. No

Memoranda

paired renal efficienlcy.

tion as gauged by the urea concentration test. 3. That the heart enlarged as a result of the strain of hypertension gets astonishingly smaller with the fall of pressure. It is difficult to give an explanation of the mechanism by which the reduction of pressure is brought about. I was encouraged to try it by my belief that sedentary occupations or lack of sufficient exercise play an important part in the aetiology of essential hypertension, and, if I may be allowed to put it figuratively, that the rusty arterioles and capillaries of sluggish muscles were a cause of elevated pressure. It was found in the series that when an appreciable degree of diminution of pressure was not obtained the urea concentration test showed im-

END

28

Ocr. 3, 1942

RENAL IMPAIRMENT DUE TO CRUSHING LIMBS

MEDICALJOURNAL

393

due mainly to reduction in glomerular filtration rate, because oliguria from this cause is associated with very high creatinine and low chloride concentration in the urine, whereas in these experiments the creatinine concentrations are low and the chlorides may be increased. Microscopically the damaged organ appears fairly vascular. Blockage of the tubules, suggested as a possible factor by the appearance of the deposit in them, should produce a tense kidney, in contrast with the striking flaccidity observed in these damaged kidneys. The deposit does not appear compact enough, nor does it occur in a sufficiently high proportion of tubules, to lead one to expect that it could reduce the creatinine output to one-quarter. A more likely hypothesis would involve release of a poison from the damaged limbs that affects the tubule cells by increasing their permeability to creatinine, urea, and other substances which are concentrated by the kidney. These substances would diffuse from the concentrated solution in the distal parts of the tubules across the tubule walls to the blood in the venules. Hastening the flow of liquid down the tubules with diuretics should reduce the loss by leakage of creatinine and so increase the creatinine clearance, an expectation which accords with observation. The main objection to regarding this as a self-sufficient hypothesis is that poisons such as cyanide or mercury salts produce an increased urine flow, due to inhibition of water reabsorption, before they produce the anuria due to increased permeability. Correspondingly, organs poisoned in this way are usually tense. This is, however, not an insuperable objection to the view that the poison here in question affects the permeability mainly. Such a poison might reach the tubule cells either from the blood"stream or, if diffusible, from the lumen of the tubule. In the latter event the poison itself might well be a substance which is concentrated in the tubules, and act the more potently in virtue of its concentration. This possibility has, however, been excluded in the following way. Partial obsftction of one kidney by an increase of ureter pressure resulted in a fourfold concentration of urine (as evidenced by creatinine-U/P ratio) compared with the unobstructed side. If the toxic agent released from the limbs had been similarly more concentrated on the obstructed side the severity of the damage should have been greater on that side. In fact, the obstructed side, after removal of the obstruction, was, if- anything, a little less severely damaged than the unobstructed side. So far as available evidence goes, the injury to the kidneys in our series of dogs appears to be of the same kind as that in man after comparable prolonged crush injury to the limbs. The essential nature of the renal damage has not yet been determined, but the evidence suggests that the main factor may be concerned with increase in permeability of the renal tubules due to a toxic agent released from the damaged limbs, while there may be an additional factor involving reduction in the rate of glomerular filtration probably due to lowering of glomerular capillary pressure.

creatinine from the concentrated urine in the tubules back into the blood. The renal damage described above is probably not

This type of respiration is seen in the terminal stage ot malignant *hypertension when pronounced albuminuria, persistent hypertension, and extensive eye changes (haemorrhages, exudates, cotton-wool patches, oedema of the disks, etc.) are present. The patient is generally quiet and lies flat on the back without a suggestion of the breathlessness of the cardiac type which previously had been well marked. A little restlessness, not continuous, is often observed; he opens his mouth frequently and breathes as though he is yawning half-heartedly. Occasionally he is irrational. Sometimes there is maniacal excitement ; at.other times a little drowsiness suggestive of a uraemic state. Uraemic twitching or convulsions were not observed. These variations in the respiratory rhythm in association with malignant hypertension have not been described before, so far as I can gather from the literature available in Ceylon. Their cause has yet to be explained. Are they due to cerebral oedema, or to the effects of toxins on the respiratory centre? Is the alteration in the chemistry of the blood responsible for them? Eyster has shown that Cheyne-Stokes breathing can be produced in dogs by a rise and fall of the blood pressure in the presence of raised intracranial pressure. In the following case, grouping of respiratory movements similar to those in the case referred to above was noticed, but each group was followed by a period of apnoea. The tracing is unlike Biot's type, but resembles that of Cheyne-Stokes respiration with the waxing phase absent. The rhythm is irregular and the depth of the respirations varies. The patient, a male sedentary clerical' worker aged 42, was admitted on March 7, 1939, complaining of occasional occipital headache, giddiness on and off, and blurring of vision. He was lying quiet, but a few days previously he had been very dyspnoeic. Examination revealed the following characteristics. Heart: heaving apex beat-in fifth space, midclavicular line; second aortic + + ; no murmurs. The lungs were clear. Blood pressure: systolic 300, diastolic 180. The brachial and radial

Case Report

*.t5."'.

VARIATIONS IN THE RESPIRATORY RHYTHM OF PROGNOSTIC SIGNIFICANCE IN MALIGNANT HYPERTENSION


BY

H. 0. GUNEWARDENE, M.B., B.S., D.M.R.E. Radiologist, General Hospital, Colombo Recently I drew attention to varlations in the respiratory rhythm in a case of malignant hypertension in its terminal stages (Gunewardene, 1938). A similar type of respiration has been noticed in cases of meningitis (Hutchison and Hunter, 1929). The characteristic feature is that the respirations are grouped; in each group the initial excursion in the tracing is the largest, the subsequent ones getting smaller, until the movements cease for a moment. This means that the depth of the respiration gradually declines as in the waning phase of Cheyne-Stokes respiration. In that case, however, there was no period of apnoea.

arteries did not feel much thickened, nor did palpation suggest such high pressure. Pulse 78, regular. Urine: scanty; S.G. 1010; albumin 0.7%; no sugar. Fundi showed oedema of the disks; flame-shaped haemorrhages, exudates, thickened arteries, very congested veins. Blood urea, 224 mg. per 100 c.cm. ; urea clearance, mean 7.26% normal. Treatment consisted of venesection; administration of sodium nitrite, theominal, etc. During his stay in hospital the blood pressure varied between 210/140 and 260/170 (not eliminating effects of drugs). He became somewhat irrational, yawned half-heartedly, and later became a little drowsy and quiet. Just, before his death (under ayurvedic treatment) on April 7, 1939, he complained that he " couldn't breathe." The accompanying illustration shows the respiratory tracing (thoracic) of this case. According to Harrison (1939), the carbon dioxide tension in malignant hypertension is abnormally low and patients with periodic breathing have arterial blood which is under-ventilated as regards oxygen and over-ventilated as regards carbon dioxide. It has also been shown that the administration of carbon dioxide abolishes periodic breathing. The fairly sudden transition of a dyspnoeic. sometimes orthopnoeic, patient into a condition of -tranquillity would suggest that changes in the chemical constituents of the blood gases and the tissue fluids play a significant part in the production of periodic breathing and the cessation of dyspnoea.
A form of variation in the respiratory rhythm associated with malignant hypertension is described. There are changes in the periodicity as well as the depth of the respiratory movements. These changes are of grave prognostic significance even when the patient does not look seriously ill, the duration of life in the cases described being not more than 6 weeks after their onset.

Summary

29

394 OCT. 3, 1942

VACCINATION IN GLASGOW DOCKS

MEBRITISH

I gratefully acknowledge the co-operation of Dr. J. R. Blaze and Dr. Cyril F. Fernando, under whose care the patient Was; also the kind services of the Physiological Department, Ceylon Medical

College.

Gunewardene, H. 0. (1938). J. Ceylon Br. Brit. med. Ass., 35, 391. Harrison, T. R. (1939). Failure of the Circulation, p. 206, Bailliere, London. Hutchison, R., and Hunter, D. (1929). Clinical Methods, p. 279, London.

REFERENCES

VACCINATION IN GLASGOW DOCKS


BY

from the pock sometimes up to the shoulder and down to the forearm. (B) A normal vaccination pock with little or no constitutional upset. (C) An immune reaction sometimes described as the papule of immunity of Pirquet. (D) No reaction. From the table it is evident that the lymph used was particularly potent, 84% of the cases showing severe or normal vaccinations and a further 10% an immune reaction due in practically every instance to a previous successful vaccination. The 58 cases which showed no reaction were all revaccinated, when only two showed an immune reaction.

GEORGE BUCHANAN, L.R.C.P., L.R.C.S. D.P.H., D.P.A. Medical Officer, Clyde Navigation Trust
AND

STUART LAIDLAW, M.D., B.Sc., D.P.H., D.P.A. Senior Assistant Medical Officer of Health, Glasgow The following is an account of an investigation into the potency of vaccine lymph and the effect of vaccination on the sickness and industrial accident rates among Glasgow dock workers.
As a result of small-pox of a severe type occurring in Glasgow, the medical officer of health, on June 29, 1942, issued an appeal for mass vaccination of the city's population. Since the disease had presumably entered through the Port it was felt that every endeavour should be made to have dock workers Vaccinated at once. At all times close co-operation is maintained between the city's health services and the Port Authority (Clyde Navigation Trust), so that the drawing-up and completion of the scheme here outlined naturally fell to be dealt with by us. The scheme was approved by the medical officer of health, the Clyde Navigation Trust, and the port regional director.

Effects on Industry We feared that mass vaccination would interfere with the normal work in the harbour and thus slow down the national effort, but this has not been so. In fact, less than 3% of all classes of workers were off work on account of vaccination. The maximum period of incapacity was one week, the great majority being back at work within 48 hours. Scrutiny of the sickness rate among dockers, office staff, and Clyde Trust employees for the 28 days subsequent to vaccination showed no increase over the normal rate prevailing at this time of year. The industrial accident rate has also shown no increase above the normal, despite .the fact that many crane drivers, capstanmen, and winchmen were vaccinated successfully, and were plucky enough to continue at work despite very sore arms.
A good previous vaccination scar was no guarantee of immunity. For example, one female who had five large foveated scars resulting from vaccination in infancy, and subsequently in 1921, had a very severe reaction. Stout persons generally had much more severe local reactions than thin persons. Elderly persons often showed severe reactions even although

Comments

The first essential was to carry out vaccination promptly and with the minimum interference with the normal working of the harbour; secondly came the necessity of informing the dock workers of the need for vaccination; and, thirdly, conveniently situated vaccination centres had to be established in the Docks. It was decided to utilize the existing gas-cleansing stations in each dock as vaccination centres and, on the day before the opening of the centres, to make use of a broadcasting van to explain the need for vaccination and to announce the time and place for workers to attend. This scheme answered extremely well, and over 60% of the workers in the Port of Glasgow availed themselves of the opportunity. The medical and nursing staff employed were directed to pay particular attention to the technique of vaccination as outlined by Sir Alexander Macgregor in his communication.

Outline of Scheme

Result of Vaccination Of the lymph used 95% was supplied by the Government Lymph Establishment, the remaining 5% being from other manufacturers. Our impression was that the Government lymph was somewhat more potent, although all the other varieties gave satisfactory reactions. The follow-up of mnany of the workers was far from easy owing to the constant changes of working shifts and the movement of gangs of dockers from one dock to another as ships arrived and departed, and we, of necessity, had to satisfy ourselves with records of 1,000 out
Table showing Results in 1,000 Cases
(Severe)
A B

previously vaccinated. Many suffered from a coryza, sometimes associated with sore throat, of about three days' duration from the 8th to the 11 th day after vaccination. In no case was the coryza severe enough to cause incapacity for work. Women reacted more severely than men in the same age groups. We found that vaccination of the lower limbs caused much more discomfort than vaccination of the upper limbs. Nine cases in our series showed a post-vaccinial rash; four of these were urticarial in type and associated with previous acne or scabies, three morbilliform, and two scarlatiniform. They all occurred between the 9th and the 10th day following vaccination and disappeared within 48 hours. We noted no case of papular urticaria, nor did any of the dock workers develop pustular rashes resembling small-pox. Neither did we see any case of post-vaccinial encephalitis nor any person who developed nervous symptoms following vaccination. Several cases showed a somewhat delayed local reaction to vaccination. This investigation' was made possible only by the willing cooperation of all classes of dock workers, and we wish to thank the medical officer of health, the general manager of the Clyde Navigation Trust, and the port regional director for permission to print
this short review.

(Normal)
719 72

(Immune)
102 10

Percentage ..

No. of cases

..

121 12

D (No Reaction) 58 6

of the total vaccinated. The accompanying table shows under four headings the results we obtained. (A) Severe reaction evidenced by constitutional upset, enlarged axillary glands, fairly extensive localized reaction, with inflammation extending

The Chadwick Trustees have arranged for the following public lectures to be given on Tuesdays at 2.30 p.m.: Oct. 6, at Roya! Society of Tropical Medicine, 26, Portland Place, W., Sir Leonard Hill, F.R.S., " The Interrelation of Clothing and Shortage of Fuel in Matters of Health "; Oct. 27, at Royal Sanitary Institute, 90, Buckingham Palace Road, S.W., Mr. W. T. Creswell, K.C., "The Forensic Aspects of Wartime Public Health Legislation "; Nov. 10, at London School of Hygiene and Tropical Medicine, Keppel Street, W.C., Bossom Lecture by Miss Jocelyn Adburgham, " Land Settlement-Its Sanitary and Architectural Aspects and After-war Possibilities "; Nov. 24, at Westminster Hospital Medical School, Horseferry Road, S.W., Malcolm Morris Memorial Lecture by Sir Arthur MacNalty, "' The Prevention of Tuberculosis in Peace and War "; Dec. 8, at Royal Society of Tropical Medicine, Dr. W. Norwood East, " The Differentiation, Prevention, and Treatment of Anti-social Behaviour Disorders." Admission to the lectures is free, and further particulars can be had from the secretary, Chadwick Trust, 204, Abbey House, Westminster, S.W.I.

END top left.

30

180 JAN. 30, 1932]

THE SIGNIFICANCE OF HAEMATURIA

LMEDICA JouRNIL

-Tubular Adenocarcinomna.-The tumour of the secreting element is the tubular adenocarcinoma. It is much more malignant, rapidly infiltrating the parenchyma in which it ariseg. It involves the perinephric tissue early, and produced metastases in the adjacent lymphatic glands. It thus comes about that the kidney, although increased in size, may have a normal contour and the drainage system be only slightly damaged, so that pyelography reveals little deformity, the cavity appearing probably dilated and at one part slightly deformed. When examined by excretion urography, however, it is demonstrated to be a functionless organ by the absence of any shadow. A rare tumour of the renal parenchyma is a haemangioblastoma. Papillary Adenocarcintoina.-The commonest malignant tumour arising from the collecting element is the papillary adenocarcinoma. Many of these were formerly mistaken for hypernephromata, and, like the latter, they formed a tumour mass, usually palpable and demonstrable. The characteristic local destruction of the drainage system, with the neighbouring calyces elongated and flattened, is observed on pyelographic examination. Functional activity as estimated by excretion urography, however, is poor. From the pelvis or calyces an epidermoid carcinoma may arise. Villous Papillorna.-The innocent tumour of the kidney that is met with clinically is a villous papilloma. It is similar to that which occurs in the bladder. Its presence can be recognized by pyelography. At first sight, when the film is inspected, the pelvis and calyces appear normal, but on more careful examination the density of the media within the cavity is seen at one part to be diminished-namely, where the villous growth is occupying the cavity. In some cases a definite filling defect is observed, and when this is combined with an interference with the entrance of the pyelographic media to one of the calyces it may be suspected that the villous growth has overstepped the borderline and become a malignant papilloma. Functional activity as estimated by excretion urography in these cases is good. Tuberculous disease of the kidney produces various appearances on pyelographic examination, which are characteristic and diagnostic. Renal Calculus.-If the shadow of a stone is seen in the renal region at the preliminary x-ray examination, its accurate localization can be simply achieved by taking another photograph with the patient lying on his side. If the concretion -be situated within the renal pelvis, this lateral view will show it lying opposite the anterior third of the body of the corresponding lumbar vertebra. If the shadow be intra-abdominal, it will be seen in front of the bodies of the lumbar vertebrae. The exact situation of the stone within the pelvis or calyces can be demonstrated by pyelographic examination.
IDIOPATHIC HAEMATURIA Essential or idiopathic haematuria is the one renal disease producing haematuria whose diagnosis is arrived at by a process of exclusion. The source of the bleeding having been localized to one kidney, no further abnormality of this organ can be revealed by any of the various methods that are employed; the urine collected is found to be sterile and free from pus cells, such as would be met with if the bleeding was from an inflamed pelvis the pyelographic contour is normal. In some cases of essential haematuria the bleeding may be most persistent. Eight years ago I operated on a man who had suffered from haematuria from this cause for twenty out of twenty-one years since it originally appeared. Nephrectomy was performed, and he has had no recurrence of the bleeding since then. Anatomically, after the kidney

was removed it appeared normal, and on histological examination all that was revealed was a certain increase of the intrarenal pelvic fat, and a varicosity of the venules within it. CONCLUSION When a case of haematuria comes under our observation it is our duty to demand that the cause of the bleeding be forthwith determined. This may necessitate a somewhat tedious examination, buit the ultimate result is certain. Fortunately, in most cases, when the cause of the bleeding has been determined, a speedy and certain cure can be obtained. In others, especially where malignant disease is present, the outlook is graver. In all of them, however, the earlier the diagnosis is arrived at the better will be the result of treatment, and in all of them, whether they are innocent or malignant, the progress of the case afterwards should be followed up by re-examination at regular intervals of three months, six months, and a year. It is difficult to persuade patients who have been pronounced cured after operative treatment of the necessity of this, and the temptation sometimes is to dismiss them with a reassurance that all is well for all time. Fortunately, in many this will prove to be correct, but in others, slight recurrence may take place, and, if so, by an accurate follow-up system such recurrence can be observed at its earliest stage and dealt with simply and promptly.

THE STROKE IN HIGH ARTERIAL PRESSURE *


A STUDY OF 159 CASES
BY

H. 0. GUNEWARDENE, M.B.., B.S.LOND.


D.,M.R.E.CANTAB.
FORIMERLY CLINICAL ASSISTANT, NATIONAL HOSPITAL FOR DISEASES
OF THE HEART, LONDON

The prominence given to the study of high arterial blood pressure seems to be ever increasing, both in the recognized textbooks and in the medical journals. Since Clifford Allbutt's lucid exposition of the conditicn called by him " hyperpiesis," Batty Shaw, Geoffrey Evans, Lord Dawson, and others have contributed to the elucidation of some of the clinical and pathological aspects of this type of high arterial pressure and of that associated with renal disease. But much remains still hazy, unknown, and unexplained. Etiology is but vaguely understood; some of the clinical manifestations have received no uniform explanation, physiologically or pathologically; and the lines of treatment indicated touch no specific methods which can be relied on to help the practitioner, who is left to turn for relief to general measures adopted in the treatment of other diseases-for example, rest, restricted diet, hydrotherapy, and the removal of septic foci. On the whole, one feels that there is some justification for striking a note of disappointment, and that, in spite of the valuable contributions hitherto made, very little substantial advance has taken place in our knowledge by which the disease can be arrested or relief be given to those in danger of being afflicted with its unpleasant sequels. One reason for this slow progress seems to he clear-namely, that the malady has not been thoroughly investigated or its early stages closely followed. Cerebral haemorrhage and heart failure as terminal events in high blood pressure may be encountered commonly enough in hospital practice, but the earlier phases and the less serious and striking manifestations are very seldom seei. Indeed, it is true to say that, by the time the grosser
*

Awarded Sir Charles Hastings Clinical Prize, 1930.

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JAN. 30,

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r THEBRITISH L MEDICAL JOURNAL

181

lesions have developed, the patient has already ceased or forgotten to look upon the earlier symptoms as part cf the same disease in its undeveloped state. High blood pressure, whatever its etiology, is common enough in general practice. No one is in a better position to study those aspects of it which throw light on its causation, and on some of the features which forecast the final doom, than the family practitioner. Methods of investigation are no doubt limited, but the mass of clinical material is heavy. No apology is made for not resorting to those special tests which can be carried out only in a fully equipped laboratory with a full staff, for the purpose of this essay is to record the clinical observations made on the so-called " stroke " as it occurs in high arterial pressure.

plegic; (3) localized-for example, tongue; and (4) diffuse. The last variety usually occurs as a terminal event, being due to a severe haemorrhage which causes sudden death, or to one which produces paralysis, first of one side of the body and then of the other. According to their duration, we may say that they are: (1) permanent, (2) present for a few days or weeks, and (3) transient. The annexed diagram gives a clear picture of what may occur on the motor side. StRO/E
PQtMOR
f

SW

SoR

DEFINITION OF "STROKE A stroke is defined in Dorland's Medical Dictionary as a sudden severe attack, as of apoplexy or paralysis." Saville considers " stroke " to be synonymous with apoplexy, for he defines each word as " a term which may be conveniently retained to indicate a sudden unconsciousness due to a vascular lesion within the skull." I propose to resort to a certain degree of licence in the use of the word, interpreting it as a " sudden severe attack," not necessarily apoplectic, and thus implying that these attacks are not confined only to the motor side. There appears to be somb justification for such a departure, for one finds Batty Shaw saying (under the heading " Persistent or temporary hyperpiesic paralysis "): " Sometimes the paralysis affects the sensory instead of motor areas, so that the patient becomes blinded without any changes being discovered in the retina or the brain." A little elasticity in my definition seems justified, not only because it helps to explain more fully the various forms these attacks take, particularly in the earlier stages of high blood pressure, but also because it helps to give a mental picture of the much-neglected sensory forms.
FREQUENCY OF STROKE Stroke occurs so commonly in high pressure, at least in Ceylon, that the scant references to it in standard textbooks is surprising. Theodore Thomson in Price's Textbook of Medicine says, " sometimes transient paralysis occurs," without any mention of the sensory attacks. Batty Shaw makes the statement quoted above in a superficial but none too impressive way. East and Bain, in Recent Advances in Cardiology, make no reference to the sensory stroke. In what they call the second stage, they say, " symptoms will rarely be experienced which refer to the pressure," also stating that the clinical features " are strikingly few "-this is in contrast to my finding th'at the strokes, all except the apoplectic, are most common at this stage. Vaquez, on the other hand, states clearly: " Transient aphasia and fleeting paresis, specially brachial monoplegia, are frequent incidents in vascular hypertension. They appear and disappear suddenly, leaving no traces, and may occur several months later." He lays some stress on the mental symptoms (uncommon in my series), which, he maintains, assume the most varied forms-for example, amnesia, mental confusion, and suicidal tendency.
MOTOR AND SENSORY STROKES Defining " the stroke" as a sudden severe attack drawing the attention of the subject of hypertension to a change in his normal motor or sensory phenomena, one can classify " motor strokes " under the main heads of the paralytic and the paretic. These can be described according to distribution as: (1) hemiplegic; (2) mono-

^tJ

PER,IANiNF1W/N

O>R

ffwD4Ys OR wEiea

Dysarthria or aphasia.

On the sensory side we get similar changes: complete loss of sensation, as in coma, and changes in sensationnamed " incomplete " for the purpose of the diagramthese being analogous to the paralytic and the paretic forms on the motor side. The distribution and duration are similar to those occurring in the motor phenomena. The diffuse form, including cases in which tingling or numbness, or " a peculiar feeling all over the head and body," has been reported, is rare. Changes in sensation have been variously described by the patients themselves, and may occur associated. with, in the absence of, or following motor phenomena. Tingling and numbness are

(coi'm)

MAthsrIs,.5 rTAWL/AV, AVWNESSs INa L/NO1SS)

described as irritating " the peculiar dry feeling of the limb, as though it had been immersed in formalin and taken out "; again, " When warm water is taken I feel it hotter on one side of the tongue; and, further, on shaving I do not feel the razor well on the recently affected side." In another case a patient complained of nurnbness of the ear, left upper limb, and distal part of the left leg after motor power had returned His description was: " as though I have placed my hand on a lump of ice and removed it." Of the ear he said: " When I j scratch my ear it feels plain.'

common. One patient of mine described the sensation as " a cotton-woolly feeling-the face feels heavy o-fi that side." A doctor, in whom a monoplegia had disappeared,

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JOURNAL

DIASTOLIC PRESSURE IN STROKE It is interesting to study very clearly at what stages in high arterial pressure the stroke supervenes. In my series of cases the stroke, sensory or motor, has not appeared in a single instance in which the diastolic blood pressure was under 1 15. In 20 per cent. of the cases the stroke-in most transient, in a few permanent, in one fatal-occurred with a diastolic blood pressure between 115 and 120. In ten out of the 150 cases death resulted from what appeared clinically to be definite cerebral haemorrhage; in nine of these, the patients were actively or restrictedly pursuing their usual occupations. Again, in nine of these ten the diastolic blood pressure was over 135, the systolic being 200 and over. In 10 per cent. of the series the transient and permanent strokes occurred in cases with a diastolic blood pressure of over 125. It seems, therefore, that sudden changes in the normal sensory and motor phenomena appear most commonly with a diastolic blood pressure between 115 and 125, and are altogether absent in cases with diastolic blood pressures under 115. Cerebral haemorrhage seems to be uncommon in patients under observation, and they are warned against any but a very quiet life. Fatal haemorrhage seems to ensue mostly in patients who carry on ordinary occupations without making allowances for their abnormal pressure. Indeed, it seems that the catastrophe of fatal haemorrhage is the one phase of high arterial pressure in which the practitioner or specialist can give little relief. There is therefore all the more urgent need to study the earlier signs and symptoms very fully, for then therapeutic measures can be resorted to in time, and where these are likely to be of no avail, relatives and dependants may be warned of the possibilities ahead, and adjustments relating to business, finance, or family matters may be made.
HEART FAILURE AND STROKF, The relation of the stroke to heart failure consequent on high arterial pressure is worth studying. My observations seem to suggest that fatal cerebral haemorrhage, or even transient strokes, are very uncommon once failure has set in or the heart has begun to show considerable enlargement, with dyspnoea and other symptoms of a tiring cardiac musculature-even though at this stage it is observed that the blood pressure, systolic and diastolic, remains high. In three cases of mine, however, there was very marked enlargement of the heart with the apex in the sixth- space- and anterior axillary line, with thickened vessels and a locomotor pulse (brachial), but with practically no symptoms referable to the heart. These three patients are reported to have died of cerebral haemorrhage. The impression is gained, in a review of my cases, that patients with hyperpiesis, showing few or no symptoms referable to the heart, with or without cardiac enlargement, are particularly prone to die of cerebral haemorrhage.
DIAGNOSIS AND PROGNOSIS In this country (Ceylon) there is a popular belief that the native doctor, so called because he practises Ayurvedic medicine, excels the practitioner of Western medicine in the diagnosis and treatment of paralysis. This is no doubt due, in my opinion, to our mistakes in the matter of prognosis in these cases, and to our failure to appreciate the transient nature of the attacks. A common procedure is as follows. A man gets hemiplegia. The nearest practitioner is sent for; he diagnoses cerebral haemorrhage and gives a gloomy prognosis, hinting at the possibility or probability of death within twenty-four hours. The blood pressure is not taken.

In despair the relatives run to the native doctor, to whom no circumstances are hopeless, and who not only promises relief, but paints the picture of a permanent cure. The case falls into the hands of the latter, and time, with the other, restricted diet on the one hand and rest works the miracle. In one case the patient gives this " Dr. X saw me, and said it was a ' spasmodic ' version: stroke. We took native treatment, as Dr. X said recovery would take three months, and it was due to high pressure." If the possibility of recovery in a few hours or days had been mentioned with confidence the practitioner would have retained his patient as well as his fees. In sensory cases the phenomena are generally classed under neurasthenia, neuritis, and hysteria, and the possibility of pressure as a causative factor is missed. Thus in this country, and elsewhere too, misdiagnosis must be
on

common.

disease, and so to correct or amplify the present findings. From the point of view of the practitioner there is everything to gain and nothing to lose by agreeing with Cabot that " the measurement of blood pressure is the most important of all the recourses that have been added to our armamentarium in the last fifteen years." When the frequent occurrence of sudden motor and sensory changes as a result of high arterial pressure is more widely recognized, the diagnosis and prognosis will be placed on more reliable data.

view-namely, to invite the study of this

These observations have been made with

one

object in
common

CONCLUSIONS AND SUMMARY the stroke In a final review of these observations in high arterial pressure, one appears entitled to infer: 1. That transient or permanent paralyses of varied distribution occur fairly frequently. 2. That the hitherto neglected sensory phenomena have a distribution similar to the motor phenomena; that they also occur frequently, and are probably caused througb an affection of the sensory areas, the pathogenesis being similar to that in the motor cases. 3. That strokes often attributed to other factors, such as shock, exertion, and emotion, are the result of an already existing pressure exacerbated by the influence of these factors. 4. That cerebral haemorrhage does not seem to occur with diastolic blood pressures of under 115 (whatever may be the systolic), and that prognosis may be based on this observation. 5. That cerebral haemorrhage occurs most commonly in people working in defiance of an already existing pressure, and without taking any account of this abnormality. 6. That any kind of paresis or paralysis is very rare in cases in which the diastolic blood pressure is under 115. If they do occur, the minimum diastolic pressure is over 115 at the time of the stroke. Strokes at this pressure are rarely fatal or permanent. The former occurs in patients with thickened vessels or other disease ; the latter in an unfortunate few, or in those in whom the causative factor is other than hypertension. 7. That cerebral haemorrhage seems to occur more frequently in those cases of hypertension which show neither marked cardiac enlargement nor symptoms, and rarely in those cases in which there are signs both of considerable cardiac enlargement and symptoms of heart
on

failure.

I am grateful to my medical colleagues at the General Hospital, Colombo, for givinlg me opportunities for verifying my observations with cases inl their wards.

END

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Another publication. {pp 37 & 38]


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