No. 4315.

MAY 12, 1906.

The Goulstonian LecturesON

AUTO - INTOXICATION : ITS RELATION TOCERTAIN DISTURBANCES OF BLOOD

PRESSURE.Delivered before the Royal College of Physicians of London on

March 13th, 15th, and 20th, 1906,

BY H. BATTY SHAW, M.D. LOND.,F.R.C.P. LOND.,

LECTURER IN THERAPEUTICS, UNIVERSITY COLLEGE, LONDON ; ASSISTANTPHYSICIAN TO UNIVERSITY COLLEGE HOSPITAL AND TO THE

HOSPITAL FOR CONSUMPTION AND DISEASES OF THE

CHEST, BROMPTON.

LECTURE I.

Delivered on March l:3th.

MR. PRESIDENT AND GENTLEMEN,-Before entering uponthe discussion of the subject of auto-intoxication it is myduty to acknowledge the high compliment that has beenpaid to me by inviting me to deliver the Goulstonian lecturesfor the present year. Dr. Goulston was impressed withthe importance of pathological study and sought to insurethat lectures should be given annually by one of the fourjunior Fellows of this College on observations resulting froma close scrutiny of pathological problems. He thereby con-tributed his support to the wholesome belief that theoreticalconsiderations should not be tolerated except when supportedby direct observation. If during these lectures I confinemyself largely to problems connected with proteid andnucleo-proteid reaction both in the natural and disintegratedstate rather than to the study of carbohydrates and of hydro-carbons, an explanation is offered that only last year Dr.W. Cecil B ’sanquet on a similar occasion to the present onedrew attention to this most interesting side of the problem.If, again, the considerations to be put before you on thepresent occasion refer largely to matters connected with thedisturbances of the circulation and the cardio-vascularmechanism, the reason offered is that during the last fewyears such important additions have been made to ourmethods of clinically investigating circulatory disorders, thatit appears to your lecturer that the time is ripe for a con-sideration of some pathological problems which now haveassumed a new aspect.

It is an experience common to us all that during ourcareers as physicians some one of the numerous problemsbrought to our notice at the bedside, post-mortem room, orlaboratory has appealed to us with peculiar insistence. The

following incident is a case in point.A married woman. aged 48 years, was admitted to Uni-

versity College Hospital under the care of the late Dr. G. V. I

Poore. She was suffering from acute bronchitis and died afew minutes after admission. At the post-mortem examina-tion, besides diffuse bronchitis and scattered patches of

broncho-pneumonia, the following observations were made.The heart weighed 14 ounces, the left ventricle was hyper-trophied, the mitral valves were sclerosed and incompetent.and the arch of the aorta showed atheroma. The rightkidney was considerably enlarged and showed the scar of aninfarct, its weight amounted to seven ounces; the leftkidney showed extreme contraction and weighed 240 grains.The total kidney substance amounted to 213’95 grammes(the total kidney substance of an average adult male amountsto 277 grammes). The presence of an infarct scar in theright kijney suggested that a similar process accounted forthe extreme shrinkage of the left kidney. To Dr. Harold S.Capper, house physician to Dr. Poore, was due the credit ofmaking a close examination of the left renal artery. Itadmitted a fine bristle with difficulty ; on carefully openingthe renal artery a patch of atheroma was found which wasresponsible for the occlusion which bad led to such aremarkable shrinkage of the left kidney.

Various points may be raised from a consideration of thiscase-e.g., on the share in the hypertrophy of the heart dueto the mitral regurgitation and the share due to the practicalW /)Q1C: z

annihilation of one kidney and the damage done to the otherSuch questions in this case cannot be clearly answered, butanother question arises and that is, Do we pay sufficientattention in the elucidation of various pathological problemsto the grave results which may follow arterial disease ? anda final problem is raised, What is the effect upon theeconomy when an organ such as the kidney disintegrates ?’It obviously must have disintegrated and the products of dis-integration must have entered the circulation by the veins orlymphatics, and it is quite a subject for discussion to considerthe possible effects of the presence in the circulation of suchplOducts of cell destruction.No doubt the majority of diseases arise from external

agencies but it is the object of these lectures to con-

sider the possible effects due to auto-intoxication, to

inquire into the changes which take place when fromany other cause the organs and tissues of the body are.made to disintegrate. Too large a field would lie beforeus if we attempted to discuss those auto- intoxicationswhich result from the suppression of functions of variousorgans or from the internal diversion of natural excretions.Moreover, it is entirely beyond the bc-’pe of these lectures fo>discuss the so-called auto-intoxications which arise frominfections occurring in the alimentary canal or other

passages connected with the exterior. In other words, theselectures will to a certain extent concern themselves with verysimilar problems to those to which Gautier and Bouchard 3 ears.ago addressed themselves. The term "leuc maines" was

applied to three groups of bodies as represented by choline,uric acid, and creatinine. No doubt from a physiologicalpoint of view many of these leucomaines have in the past"been regarded as very mildly toxic agents, but it is fairto assume with Pnuger that in pathological conditions,especially in cases where elimination is interfered with,the accumulation of the products of cellular disintegration,whether of a physiological or pathological origin, may haveharmful effects.At the present moment there are various reasons why

pathology should be interrogated as to its answer to the-

question what symptoms and signs met with at the bedsidemay be attributed to auto intoxication in the above restrictedsense. The principle is admitted mostwidely, but the exactevidence supporting such theory is, to say the least, not set,out in our systems of medicine as clearly as the frequencywith which we do not hesitate to invoke auto-intoxicationdemands. Another reason for discussing the problem is

undoubtedly due to the fact that we are not able to tracedirectly to bacterial invasion some of the manifestationsmet with clinically : observers are quite sure that someeffects are due to quite different causes than bacterialinvasion. Toxins of cellular origin have been found toexist and brilliant discoveries have of late years been madein the domain of cytotoxins and of the interaction of organsderived from different animals upon one another. Such a

subject, however, could not possibly form any part of acourse of lectures on auto-intoxication. Much more excuse,however, is found for such lectures as the present one, onthe grounds that in the domain of chemical physiologygreat advdnoes have been made not only abroad but in this

country. The reaction of derivatives of the disintegrationof cells is a subject which appears, ever since tLe discoveriesmade by the late Dr. Wooldridge, to have excited particularinterest in this country and in my endeavours to approachthe subiect of auto intoxication I find that his researchesform the foundation of a great deal of modern chemical

physiology and largely, I venture to think, because with suchclear insight he saw what an immense importance such asubject has for pathology. If a large part of these lecturesis devoted to the subject of blood pressure in disease, myexcuse must be that the remarkably accurate estimate givenby the sphygmomanometer of human blood pressure hasgiven such an impetus to the investigation of clinical bloodpressure that we are flooded out with a large number of factsbut are hardly able to appreciate their significance.With this brief introduction I may pass on to the closer

study of auto-intoxication-i.e., to the study of the effects ofthe dissolution of cells of various organs and tissues as shownby the toxic effects of their products, rest)icting myself inthe main to the consideration of the products of proteidand nucleo-proteid degradation, including not only the deepdegradation products but those more vital agencies a study

1 Lockhart Mummery : Proceedings of the Physiological SocietyFeb. 25th, 1905, xxiii.

1296 DR. H. BATTY SHAW: AUTO-INTOXICATION, ETC.

of which is only possible when we examine the effects pro-duced by fresh tissues-i.e., tissues which, though dis-

integrated by mechanical means, may be considered stillliving tissue in so far as the formation of their deep dis-integration products has not yet begun.

BLOOD PRESSURE IN HEALTH AND DISEASE.

Very considerable interest has been aroused in recentyears in the clinical observations of blood pressure. Therange of variations in different diseases is considerableand great departures from the normal have been observedin various medical disorders. I propose to bring beforeyou some observations made on patients under the care

of my colleagues. Care has been taken to follow theprecautions laid down by various writers on the subject.The observations were taken twice daily at about 9-10 A.M.and 8-10 P.M. In all cases, where possible, the patientswere recumbent and the arm was so arranged that thatpart of the limb-viz., the upper arm-on which the sleeveof the sphygmomanometer was applied was on the levelof the heart. In some cases recumbency was impossible:then the arm was raised by means of pillows so that theupper arm and heart were on the same level. The instru-ment used throughout has been the Riva-Rocci sphygmo-manometer as modified by von Recklinghausen.’ The latterobserver discovered that the width of the armlet or man-chette was of importance ; if too narrow the pressure readingwas considerably higher than if a wider armlet was used.The size of the sleeve which von Recklinghausen found tobe the most satisfactory was for an average adult’s arm10 centimetres; a width of 15 centimetres was suitable for allsizes of arms. The armlet used in the present observationsconsisted of two parts, a rubber bag which was immediatelyapplied to the arm and a metal band which encircled thebag ; the former measured 13’ 97 centimetres and the latter12 centimetres in width. The tubing was stiff rubber,outside diameter half an inch and diameter of bore three-sixteenths of an inch. As much precaution as possible wastaken to prevent any excitement on the part of the patientwhen the reading was taken. The readings at night werein a large proportion of cases taken by members of thenursing staff of University College Hospital ; in themornings the observations were mostly personal ones. Theblood pressure observations represent the systolic pressure,air being pumped into the hollow armlet until the pulse ofthe arm was obliterated and then observation was made ofthe height of a column of mercury in a manometer connectedwith the hollow armlet; that height was recorded at whichthe pulsation of the radial artery returned ; the readings wererepeated once or twice before being recorded and in manycases until accuracy was secured to the observer theobservations were checked by another observer. In allcases, unless otherwise specified, there was complete absenceof oedema or muscular rigidity.Thayer has constructed a table of the blood pressure in

276 healthy individuals arranged in decades. Making acorrection of 25 millimetres for the use of a 5’ 0 centi-metre armlet in the cases he observed after ten years of

age, the variation is shown as in the accompanying chart.

f00..., I

I I I I I I

I-IOYrs. 10-20Yrs. 20-30Yrs. 30-40Yrs. 40-50Yrs. 50-60Yrs. 60-10Yr3.(37Cases) (87Cases) (89Cases) (37Cases) (20Cases) (5 Cases) (I Case)Diagram showing rise of systolic pressure with increasing

years in healthy persons.

The rise of pressure in later years may be due to a

variety of causes of pathological nature ; the common visibleaccompaniments of advancing age-viz., arterio-sclerosisand cardiac hypertrophy-are well known, but as it is also

2 Von Recklinghausen : Archiv für Experimentelle Pathologie undPharmakologie, 1901, Band xlvi., S. 78.

3 Thayer : American Journal of the Medical Sciences, 1904, vol. cxxvii.,p. 391.

known that old age may occur without these accompani-ments, it must be felt that the rise of pressure so often metwith in old age may be due to certain causes of which atpresent we are ignorant and which are of a pathologicalorigin. Through the courtesy of Dr. Harley Brooks of theMile End Infirmary it has been possible to add furtherobservations on the blood pressure of elderly people. 23 menwere examined between 10 A.M. and 12 noon and the bloodpressures were taken in the manner already described. Twocases were observed at ages between 40 and 50 years; twobetween 50 and 60 years; seven between 60 and 70 years;four between 70 and 80 years ; and eight between 80 and 90years. The average pressure of the seven cases between 60and 70 years was 155’ 8 millimetres, which agrees with theone case recorded in Thayer’s chart; between 70 and 80 yearsthe average pressure was 166 millimetres ; and between 80and 90 years 155 - 3 millimetres. Most of these patientswere bed-ridden; the observations made are shown inTable I.

TABLE L-Systolio Blood Pressure in Infirmary Patients(Men in Recumbency).

Three only of these cases show moderate pressure. Case 1.aged 49 years, showed a pressure of 88 millimetres ; it willbe noticed that he had tuberculosis of the lungs, a diseasewhich is associated with low pressure. Case 7, aged 65 years,had a pressure of 110 millimetres ; Case 10, aged 66 years,had a pressure of 123 millimetres ; and Case 19, aged 81years, had a pressure of 107 millimetres ; in this latter case itis to be observed that the urine was offensive. Despite thewant of uniformity in the readings of the sphygmomano-meter these observations confirm the view that with in-creasing years there is generally a rise of arterial pressure.To mark the contrast between this hypertension of age andpossibly disease with the pressure met with in an earlier periodof life with health reference was made to the blood pressure ofyoung healthy males in the persons of 42 schoolboys attend-ing University College School. I take this opportunity to thankDr. H. J. Spenser for his courtesy in allowing these observa-tions to be made: These boys were so healthy that they wereable to take part in gymnastic exercises. The time chosen

1297DR. H. BATTY SHAW: AUTO-INTOXICATION, ETC.

for examination was between 10.30 A.M. and 12.40 P.M. The

boys were immediately before examination engaged in classwork, not in gymnastic exercises. The average blood pres-sure in recumbency of six boys between 112 and 12 years ofage was 104’ 5 millimetres; between 122 and 13t years,105’5 5 millimetres ; between 13t and 14! years, 107 5 milli-metres ; between 142 and 15t years, 108’ 8 millimetres ;between 152 and 162 years, 124’ 1 millimetres ; between 162and 172 years, 118’ 8 millimetres ; and between 172 and 182years, 111 6 millimetres. (Table II.)

TABLE n.-Systolic Blood Pressure in Apparently HealthyYoung Afales (in Reezcmbenay).

Here, again, it is very obvious that there are variations Iin the systolic blood pressure of different individuals of thesame age and from the above table it willbe seen that there is no steady advancein pressure in accordance with the ageof these youths ; no doubt some of thepressures are unusually high and may beattributable to a little excitement on the

part of the boys examined. Precautionswere, however, taken to avoid these dis-turbances as much as possible, the

pressure being first taken in the sittingposture to accustom them to the instru-ment and then after from three to fourminutes’ recumbency they were examinedagain and the above results obtained. Itis well known that a very different read-

ing is given after the same mentalexcitement in individuals of differenttemperament, being higher in the moreexcitable.

BLOOD PRESSURE IN DISEASE.

Janeway 4 states that in adult life thepressure is in men before 50 years of agefrom 100 to 130 millimetres and after 50years from 130 to 145 millimetres, andin women about 10 millimetres less usingthe 12 centimetre armlet. Observa-tions, 68 in number, have been madein various forms of disease in the s

wards of my colleagues at Univer- PREsity College Hospital. Taking Jane-way’s figures as a guide, 42 cases

were found to have systolic pressureswithin the limits of ordinary health,and these included under a clinicaldiagnosis : cirrhosis of the liver,four cases ; valvular disease, eight

4 Janeway: The Clinical Study of BloodPressure, 1904.

oases; diabetes mellitus, four cases; bronchitis andemphysema, four cases; aneurysm and arterio-sclerosis,two cases; tuberculosis of the lungs, two cases; otherdiseases, 18 cases. Under the last category are included

dyspepsia, ascites following removal of ovarian tumour,meningitis, disseminated sclerosis, neurasthenia, gastriculcer (two cases), gall-stones (without jaundice), tabesdorsalis (two cases), alcoholic neuritis, ha3maturia,acute rheumatism, otitis media, pernicious anaemia,exophthalmic goitre, lymphadenoma, and trypanoso-miasis.A second group of cases of abnormal blood pressure in-

cludes two subdivisions : 1. A number of cases in whomthe blood pressure was lower than normal. They were 14 innumber and included the following : acute bronchitis (fatal),arterio-sclerosis (? abdominal aneurysm), acute pneumonia,cirrhosis of the liver, advanced carcinoma of the stomach(two cases), jaundice (two cases), empyema, malaria, statusepilepticus, chronic Bright’s disease, aneurysm of thearch of the aorta, and a case of unusual character inwhich the only signs were pain about the root of thenose associated with a hard cedema of the neighbour-ing skin, independent of suppuration of the frontal sinuses,&c. (See Charts 1 and 2.) 2. A number of cases in whomthe blood pressure was higher than normal; these were 12 innumber.CASE l.-A man, aged 80 years, was taken to the hos-

pital shortly after an attack of giddiness and fainting whichoccurred whilst walking. He was found to be consciousbut there was paresis of the left arm, leg and face.The pulse was 90, of large volume and of hightension. There were present marked arterial disease andan accentuated second aortic sound. The urine was

reduced in amount, showed a specific gravity of 1018and a cloud of albumin. The blood pressure is shown inChart 3.A post-mortem examination was made eight days after

admission. There was no cerebral hemorrhage : the arteriesat the base of the brain were markedly atheromatous anddilated. There was no thrombosis in the larger cerebralvessels ; the sinuses were normal; the convolutions were

apparently normal. The heart weighed 16 ounces ; thevalves were normal. There was atheroma of the aorta, thelimb-vessels, and the coronary arteries. With regard to

CHART 1.

A man, aged 41 years; carcinoma ventriculi.

1298 DR. H. BATTY SHAW: AUTO-INTOXICATION, ETC.

the kidneys, the right weighed four ounces and the left fourounces ; the capsules were adherent ; the cortex was reducedto one-eighth of an inch, the substance was tough, and cystswere present.

CHART 2.

70 L I I I

A man, aged 35 years; oedema of the face.

6íCASE 2 (vide Chart 4).-A man, aged 41 years, was

admitted for headache and basmaturia. The patient wasemphysematous and the body was well covered ; no clinicalsigns ;of hypertrophy of the heart were present; there was&light tortuo3ity of the vessels. The quantity of urine varied

CHART 3.

no z ,

A man, aged 80 years; uraemia.

from 20 to 58 ounces daily; it was of specific gravity 1010to 1015 and contained albumin from 0 ’ 15 to 0 ’ 175 per cent.;it contained blood and a variety of casts. (Edema was

slight and confined to the lower trunk and legs. The head-ache gradually disappeared and the hasmaturia became less.

The patient was discharged at his own request, the albumin-uria being still present; the oedema had disappeared.CASE 3 (vide Chart 5).-A lad, aged 17 years, was

admitted for albuminuria and slight oedema of the legs.He had had scarlet fever three years previously and sixmonths later his legs began to swell and had remainedswollen ever since. The first sound at the apex was boomingin character and the aortic second sound was accentuated;the vessels of the arms were more rigid than usual. He

passed from 22 to 70 ounces of urine daily ; it was of cpecificgravity 1005 to 1015 and contained albumin from 0 16 to0’ 3 per cent. He was discharged feeling much better andthe dropsy had disappeared.CASE 4.-A man, aged 69 years, was admitted for sensory

aphasia of some months’ duration ; there was no associatedhemiplegia. Rigidity of the vessels was very marked ; the

CHART 4.

A man, aged 41 years; acute Bright’s disease.

aortic second sound was accentuated and there was 0’ 1 percent. of albumin in the urine ; he passed from 26 to 53ounces daily. The temperature was normal. His systolicblood pressure was constantlv above 160 millimetres andreached as much as 184 millimetres. His only complaintwas the aphasia and he was ultimately discharged.CASE 5.-A man, aged 21 years, was admitted for severe

dyspnoea and orthopnoea ; there was oedema of the lowerextremities which increased till death supervened. Theamount of urine passed varied from 30 to 70 ounces andgradually was diminished to 6 or 12 ounces; it was ofspecific gravity from 1010 to 1020 ; the albumin varied from0 ’ 4 to 1’ 5 per cent. The blood-vessels were not abnormallytortuous or hardened ; there was no marked accentuation ofthe aortic second sound ; the temperature was normal. Theblood pressure varied from 125 to 144 millimetres andtowards the end underwent rapid diminution, becomingsubnormal ; the dyspnoea intensified till death.At the post-mortem examination the heart was found to be

greatly enlarged and dilated, weighing 19 ounces. Thekidneys gave evidence of being much tougher than usual;they weighed seven ounces each.

1299DR. H. BATTY SHAW: AUTO tNTOXICATION, ETC.

A lad, aged 17 years ; chronic Bright’s disease (? contracted kidne:

CASE 6.-A man, aged 43 years, was admitted sufferingfrom uraemia. He was dyspnoeic and had a pulse-rate offrom 23 to 34 beats per minute; the temperature wasnormal. The brachial blood-vessels were markedly thick-ened and tortuous. Only 20 ounces of urine were passedduring the 25 hours he survived. It was loaded with albu-min and casts were abundant. Five blood pressure observa-tions showed 160, 140, 162, 163 millimetres, and the lasttaken at 12 midday was 160 millimetres. At 1 o’clock thepulse could not be felt and at 1 30 P.M. the patient died.At the post-mortem examination the heart weighed 27

ounces ; the left ventricle especially was greatly dilated andhypertrophied ; the coronary arteries and aorta were athero-matous and the limb vessels were thickened. The kidneysweighed six ounces each ; the capsule stripped off readily;the cortex was one eighth of an inch in depth ; the renalarteries were thickened and atheromatous.CASE 7.-A man, aged 32 years, was admitted with ursemic

dyspncea and almost complete suppression of urine--onlyfour ounces in two days. Albumin, blood, and casts were S’Ipresent in the urine and the patient was slightly cedematous PREin the lower extremities, had diarrhoea and sickness, and there

’

was also some fever. The maximum impulse of the heartwas in the fifth space, external to the nipple line ; the secondaortic sound was accentuated. Four observations were madeon the blood pressure : Oct. 30th, evening, 187 millimetres ;Oct. 31st, morning, 167 millimetres ; evening, 162 millimetres ;and Nov. 1st, at 10 A.M., 88 millimetres. Death occurredseven hours later.At the post-mortem examination the kidneys were found

to be red, granular, and contracted, and contained cysts ;the cortex was greatly reduced ; each kidney weighed fourounces ; the renal vessels were narrowed. The heart weighed14 ounces ; the coronary arteries were fairly healthy ; therewas very little atheroma in the aorta or vessels of the limbs.CASE 8 (vide Chart 6).-The patient was a man, aged

39 years. He was admitted for headache and sickness ; hehad also had puffiness of the feet for three weeks. Theurine was albuminous but there was no sign of arterialdisease and the heart revealed no signs of hypertrophy.The temperature was normal. The symptoms graduallyabated and he was discharged. The chart shows the eleva-tion and gradual fall of the blood pressure in acute Bright’sdisease.CASE 9 (vide Chart 7).-A married woman, aged 41 years,

was admitted for headache, oedema of the ankles, andalbuminuria. There were no signs of cardio-vascular disease.There was some fever. The urine varied from 15 to 43 ouncesdaily ; it was of specific gravity from 1013 to 1028. Albuminvaried from 0’12 to 0-20 per cent. The blood pressure varied,falling during her stay in the hospital but rising abovenormal again prior to her discharge.CASE 10 (vide Chart 8).-A man, aged 43 years, was

admitted for pains in the chest and headache and for some

dropsy in the feet. He had had a

similar illness three years previously andhad passed blood in his urine. Therewere no marked changes in the cardio-vascular system. The urine varied from47 to 92 ounces; on three days it was,however, much less-10, 20, and 18ounces respectively ; it was of specificgravity from 1010 to 1027. On admis-sion he was passing 0’ 33 per cent. ofalbumin but on his discharge there wasonly a trace ; blood was passed on severaloccasions. There was a copious deposit

, of casts on admission. He developedsevere uraemia with convulsions and wasbled and infused. He left the hospitalquite free from symptoms.

I CASE 11 (vide Chart 9).-A man, aged55 years, was admitted for extensive leadpalsy and was found to have a bloodpressure which ranged from 155 to 177millimetres. This gradually subsided tonormal. The arteries were very tortuousand the second aortic sound was accen-tuated ; the maximum impulse of theheart was obscured by emphysema. The

specific gravity of the urine was from1015 to 1022; a slight trace of albuminwas present. He was discharged relievedto a certain extent.

CHART 6.

A mm, aged 39 years ; acute Bright’s disease.

1300 DR. H. BATTY SHAW: AUTO-INTOXICATION, ETC.

CASE 12 (vide Chart 10).-A man, aged 36 years, wasadmitted for general debility and for wrist drop; he showeda lead-line. The heart was not hypertrophied. The urinewas of specific gravity 1012 to 1020, normal in amount,

CHART 7.

vtU .......

0

140

ov ——————————————————————————————————

A married woman, aged 41 years ; subacute Bright’s disease.

and no albumin was present. The arteries were not par-ticularly rigid. He was discharged relieved.The next case, one of chronic Bright’s disease, is described

at this stage, though the patient had atfirst normal and then subnormal bloodpressure.CASE 13 (vide Chart 11).-A widow,

aged 49 years, had attended UniversityCollege Hospital since August, 1903,with dropsy and ascites. The heartwas enlarged and the aortic secondsound was accentuated. The amountof urine varied from 25 to 77 ounces but s ’(a few days before death it became much PRE

reduced; the specific gravity was from1015 to 1019 ; the albumin varied from2’5 to0’8 8 per cent. The temperaturewas normal. The patient died comatose.

Post mortem the heart weighed 18ounces and the left ventricle was greatlyhypertrophied ; the aorta and blood-vessels were free from atheroma andthe radial vessels were not thickened.The right kidney weighed five and ahalf ounces and the left six ounces.

The cortex of the kidneys was reduced ; NO

the substance of the organs was tough ; Ethe renal vessels showed no sign of

thickening. There were very well-marked chronic perihepatitis andchronic peritonitis.

Consideration of the above 68 casesleads to the conclusion that in diseaseof various kinds the blood pressure showsa great variation both in each individualand also comparing one case withanother ; 42 cases show a blood-pressurewhich so far as our knowledge goesat present is well within the normallimits. 14 cases, however, show pres-sures which are distinctly lower thannormal and there remain 12 cases inwhich it is- higher. It cannot be denied

out of place on an occasion like the present to call attentionto it. Of the 12 cases of hypertension all except one wereassociated with the occurrence of albuminuria-a fact whichat once calls to mind the association of hypertension andrenal disorder. The excuse which is offered for bringingthis fact into prominence is that in these particularcases the test of the existence of hypertension has beenof an instrumental nature-an element of greater precisionhas been added to the observations by the fact that theincreased tension had been detected by other means thanthe " tactus eruditus " of the trained finger. The earliestrecords (made by means of a sphygmomanometer) of the asso-ciation of maintained hypertension with renal disease weremade by Riva-Rocci in 1897-1898.5 No one who has com-

pared the results obtained from a digital test of increasedtension as compared with an instrumental one can fail toacknowledge that we have been deceived in the pastfrequently and have by digital examination inferred thathypertension was present when in reality rigidity of vesselwall was alone responsible for such impression.Returning to the consideration of the 12 cases of hyper-

tension renal disease was present certainly in 11, it may havebeen absent in one. As shown by post-mortem examinationgrave renal disease was present in four of the cases and

using purely clinical tests a similar condition of renal dis-order may be conjectured in the case of the remaining sevenor even eight. Remembering the close connexion existingbetween renal disease and intoxication by lead, it may even bethought highly probable that renal changes were present inCase 12, in whom hypertension was present but was notassociated with albuminuria. It is possible that this raisedpressure was an example of the effect of hard muscular workand that rest in bed had led to the fall. The occurrence ofa high blood pressure persisting after muscular effort is,however, disbelieved by good observers. In the series of 12cases of hypertension, owing to the precautions taken, theinfluence of so-called " functional causes of hypertensionmay be excluded ; so, also, the influence of drugs may beruled out of consideration and in no cases were there reasons

CHART 8.

A man, aged 43 years; chronic Bright’s disease; exacerbation,

that possibly there are many causes of a quite differentnature which may be responsible for the departures fromthe normal of the latter 26 cases. One definite featurestands out in great prominence, however, and it must be saidhas been noticed for many years past, so that it may seem

j

I to believe that cerebral compression was operative as a

causative factor.

5 Riva-Rocci : La Tecnica della Sfigmomanometria, Gazzetta Medicadi Torino, 1897, Nos. 9 and 10.

1301DR. H. BATTY SHAW: AUTO-INTOXICATION, ETC.

CHART 9.

A man, aged 55 years ; lead palsy.

THE CREDITED CAUSES OF HYPERTENSION.The problem, therefore, resolves itself into a solution of

this difficult question, How is hypertension, such as isshown by the above 12 cases, to be explained ? The necessityfor finding an explanation is patent to everyone and has foryears past been one of the unsolved riddles of pathology. Ithas, no doubt, been approached in different ways, for patho-logists in the past attacked a different sort of problem-they

CHART 10.

A man, aged 36 years; debility; plumbism.

endeavoured to find a cause for cardiachypertrophy and especially left-sidedcardiac hypertrophy, as shown at thebedside or in the post-mortem room.Thanks to the sphygmomanometer wecan certainly detect the accompanimentof, or as we have long believed, a phe-nomenon antecedent to, cardiac hyper-trophy-viz., exalted blood pressurewhen clinical examination from variousreasons is unable to detect any cardiachypertrophy. Bright was able to statethat cardiac hypertrophy may occurwithout any valvular disease and with-out any thickening of the aorta. Thefrequency of left-sided hypertrophy atonce suggested that there was some

possible local cause for the phenomenon.The blood was so altered that itacted as a direct stimulus on theheart itself, so he says, or it in-fluenced the fine capillary vessels insuch a way that the heart was com-

pelled to hypertrophy in order todrive the blood through the contractedvessels. Within limits the cardiac

hypertrophy and kidney disease werecommensurate. This altered character of the blood wasnot accepted by many observers as a cause of hypertrophyand it was even suggested that it was possible for thecardiac hypertrophy to be a cause of the renal disease. Thearterial disease was considered by others to be the causeboth of the renal disease and of cardiac change. -

With regard to cardiac hypertrophy occurring in co nexionwith renal disease, it is acknowledged that it is the leftventricle which is enlarged ; if the right ventricle is enlargedthen some other factor is probably responsible for it. Ex-

periments have been carried out in order to show whether

CHART 11.

A woman, aged 49 years ; chronic Bright’s disease.

1302 DR. H. BATTY SHAW : AUTO-INTOXICATION, ETC.

the kidney disease is primary and the cardiac hypertrophyand vascular disease secondary or whether the reverse is thecase. Rosenstein 6 was able to show that the removal of onekidney in rabbits and dogs produced no rise of pressure inthe aortic system and no hypertrophy of the heart. Otherobservers have confirmed these results entirely, whilstothers have found that in some cases at least cardiac

hypertrophy occurs. De Dominicis, who found hypertrophyof the heart after ligature of one renal artery, attributes thecardiac hypertrophy not to the fact of the ligature of therenal vessels on one side but to some change in the blood.Traube considered the cardiac hypertrophy to be due to theincreased resistance produced by the obliteration of numerousvessels in the contracted kidney and by a diminished outputof water. Both these explanations fail, for it is knownthat the average blood pressure in the aorta is not

permanently raised by ligaturing the two renal arteries,and in contracted kidney the output of water is notreduced but even increased. Bamberger has attributedthe cardiac hypertrophy to an attempt on the partof the heart to correct a condition of hydr2emicplethora, but this latter has not been shown to existin such cases. The late Dr. Fagge explained the cardiachypertrophy by a modification of a view put forwardby Cohnheim. So little healthy kidney substance isleft that the heart is obliged to drive all the bloodthrough a much smaller filter-bed and as a result becomeshypertrophied. Israel on the strength of his findings thatrabbits fed with urea developed cardiac hypertrophyconcludes that retained products are the cause but thefurther observation made by him that the kidneys were alsoenlarged makes it difficult to explain cardiac hypertrophyin contracted kidneys. It is known that contracted kidneysare not always associated with cardiac hypertrophy, so thatmerely mechanical explanations are not satisfactory, and theview originally propounded by Bright that there is a

stimulating substance circulating in the system which actsupon the circulatory system is favoured by many writers.Senator 7 suggests that the constituents of the urine causeby retention an increase of pressure and that all thesesubstances acting together may possibly be a completeexplanation of the increase of pressure. It may, however,be said in answer to this that the urine removed immediatelyfrom an animal’s bladder and injected into its own vascularsystem produces not a pressor but a very marked depressoreffect, and yet in this case all the urinary constituents areacting in unison which rather suggests that this retention ofurinary constituents is not the cause of cardio vascularchanges. Moreover, it is known on experimental groundsthat the output of urea may be greatly increased whenthe amount of kidney substance is greatly reduced byablation. s

It is possible, however, for the cause of cardio-vascularchanges to be found in other directions than in the influenceof retained products occurring in renal disease. The observa-tions of Hasenfeld 9 point to the possibility of left-sidedcardiac hypertrophy occurring only when there is advanceddisease of the sp’anchnic arteries or of the aorta above thediaphragm.The use of the sphygmometer shows that it is possible to

establish clinically a group of cases in which there is main-tained high blood pressure but little or no signs of arterio-sclerosis or of renal disease : cardiac hypertrophy may bepresent to some extent. This group constitutes those casesof latent angio-sclerosis described by von Basch or of pre-sclerosis as described by Huchard. Useful as may be this

recognition it cannot be said for certain that renal diseaseis absent in these cases ; the absence of signs of arterialdisease, of cardiac hypertrophy, or of albuminuria is not con-clusive evidence that the kidneys are healthy. I venture toinsist upon this point, for the evidence drawn from the abovelist of clinical cases of raised arterial pressure tends to showwith one exception that all the cases of hypertension observedby me are associatad with renal disease as shown byalbumin, &c. The fact that one case (Case 12, Chart 10)revealed no signs of renal disease and yet had highpressure may be explained on the ground that he was alabouring man and that the rest in bed had very shortly

6 Rosenstein : Virchow’s Archiv, 1871, Band liii., S. 141.7 Senator : Die Erkrankungen der Nierin, 1902.

8 Dr. J. Rose Bradford : The Goulstonian Lectures, THE LANCET,March 19th (p. 765) and 26th (p. 843). and April 2nd (p. 916), 1898.

9 Hasenfeld : Deutsches Archiv für Klinische Medicin, 1897, Bandlix., S. 193.

been followed by a fall to normal; as already stated the viewthat effort is capable of producing maintained arterial tensionhas been denied, so that this explanation of the case is notassured. Early sclerotic changes in the splanchnic vesselsare said to be the cause of these cases of pre-sclerosis, butthe fact that this patient with ordinary rest in bed and nospecial treatment got rid of his high pressure suggests thatthere is still some other explanation for a rise of pressurewhich, as in this case, was found to fall, not at once, but bythe end of two days to normal.To sum up, there is a general admission that the explana-

tion of increased arterial tension and of cardiac hypertrophyindependent of valvular disease and obstruction of the pul-monary circuit is not satisfactory. We do not possess anyclear ideas of the nature, origin, and mode of action of thehypothetical irritant substance which has been invoked toexplain hypertension and which may have been the operativefactor in Case 12 above described, as well as in the cases ofhypertension associated with albuminuria. During the lastfew months I have set myself the task of making a directappeal to biological tests for an explanation of the variousdifferences of tension as shown by sphygmomanometerobservations at the bedside. The idea was that it was

possible for certain substances to be extracted from theorgans in different diseases, which acting on the circulationof the patient would be capable of producing those rises orfalls of blood pressure which constitute the abnormalities ofthe above list of 68 cases. For this purpose four cases wereselected in the wards, in whom there were differences of £blood pressure (Table III.).

TABLE III.

20 cubic centimetres of blood were removed from a veinof the forearm by puncture with a needle ; the blood was atonce placed in ice and within three hours after preparationby grinding up with sand, when clotting had taken place andafter diluting with 1 in 3 sterilised salt solution (0’ 86 percect.), it was injected in four cubic centimetre doses into thefemoral vein of a cat weighing 3100 grammes ; the bloodpressure was taken from the carotid artery ; anaesthesia wassecured by means of ether and the respiration was spontane-ous ; the vagi were intact. The changes above recorded werevery brief and, as will be seen, do not give any support tothe view that in hypertension of the arterial system (Cases3 and 4) such small quantities of blood of patients with hightension contain a pressor substance capable of exerting itsinfluence on the cat. In Case 1, who was free from arterialdisease, cardiac hypertrophy, and albuminuria, there waseven a rise and the same result was obtained in anotheranimal injected with the same blood.

Observations on tiss1le extracts and their pressor or d6,-

pressor effects.-Since the discovery by Schafer and Oliver ofthe pressor effects to be obtained by preparations of themedullary substance of the suprarenal gland, considerablework has been done in the study of other animal extractswith reference to their effect on the blood pressure. Oneother substance stands out prominently as being capable ofproducing these changes-viz., the pituitary body, thepressor substance being present in the posterior lobe. Con-siderable speculation has been made with the object ofshowing that the suprarenal extract or adrenalin is possiblycapable of exerting during life an influence upon the bloodpressure-indeed, that its special duty is to maintain anormal level of blood pressure by a process of internalsecretion. The great objection to this view has beenthat the blood of the suprarenal vein does not appear toexert much, if any, effect on the blood pressure and thatablation of the suprarenal body and obstruction of tre

1303DR. H. BATTY SHAW: AUTO-INTOXICATION, ETC.

suprarenal vein do not much influence the blood pressure.Szymonowicz 10 asserts that he has seen, several hours afterremoval of the suprarenal bodies, a fall of the blood

pressure. It is, of course, difficult to say how much of thiseffect was due to other causes than loss of suprarenal secre-tion from the circulation. Lewandowsky 11 has found normalblood pressure 30 minutes after ligature of the sup-arenalvein. Camus and Gley 12 failed to establish any rise ofblood pressure after closure of the suprarenal vein or riseafter opening it and when they injected the blood from thesuprarenal vein of one animal into the circulation of anotherthey found a rise only if the injection was quickly made andwas entirely absent when such small quantities are injectedas are likely to reach the vena cava normally through thesuprarenal vein More recently Blum 13 has made furtherexperiments and agrees that suprarenal blood gives no rise ofpressure. The confusion caused by the different results hasbeen attacked by Ehrmann 14 who, abandoning the blood pres-sure effect of suprarenal substance as a guide to its presencein the blood, has made use of a physiological test developed byMelzer. 15 Melzer states that the effect of adrenalin as adilator of the pupil is a more delicate test than the effect onthe blood pressure and finds that the pupil is dilated on theapplication of adrenalin in such dilution that blood pressureeffects cannot be secured. By using the pupil reaction as aguide Ehrmann was able to show that the blood of the supra-renal vein contains adrenalin. The question whether thesuprarenal gland is really an organ in which adrenalin ismanufactured or whether it merely acts as a magazine for thestorage of substances elaborated elsewhere has been ap-proached by Abelous, Soulié, and Tougan.16 A pulp wasmade of suprarenal glands by rubbing them down innormal saline solution (1 in 2), chloroform was added to

prevent bacterial growth, and one portion was exposed toa temperature of 0° C. and another to 40° C. Adrenalinwas estimated colorimetrically by means of iodine. The

pulp kept at 40° C. contained more adrenalin than that keptat 0° C. With care they found it possible to separate medullafrom cortex in the suprarenal gland of sheep. The cortexwas pulped and one part exposed to 0°C. and an equalpart to 40° C. That kept at 40° C. was found to containmore adrenalin than the other. These workers thereforeconclude that adrenalin is formed in the cortex and accumu-lates in the m3dulla, supporting the view of an internalsecretion.

Accepting the position that adrenalin is diverted into thecirculation and is therefore able to exert its action on blood-vessels, the stimulation taking place at the junction ofmuscle and nerve,17 the question may well be raised as towhether there is any evidence that the increased vasculartension met with in certain clinical cases can be associatedwith an increased discharge of adrenalin into the circulation.Aubertin and Ambard 18 state that they have found that con-tracted kidney, enhanced arterial tension, and arterio-sclerosis go hand-in-hand with hyperplasia of the corticalsubstance of the suprarenal glands. They based their

’opinion on the post-mortem examination of eight cases inwhich nephritis and raised pressure had been present, andthey controlled their results by examination of 19 othercases, seven of nephritis without hypertension and 12 casesof various disorders not associated with hypertension. Infour of the eight cases the cortex of the suprarenal gland washyperplasic and the medullary substance reduced and adeno-mata were present three times in the suprarenals. Aubertinand Ambard conclude that arterio-sclerosis is not the resultof the hyperplasia of the cortical substance, but that theyboth constitute a reaction to some poison which is as anassociation or result of renal disease not properly excreted.Their observations also confirm the view that renal hyper-tension is not due to an excessive internal secretion of the

suprarenal gland.10 Szymonowicz: Pflüger’s Archiv, 1896, Band lxiv., S. 97.

11 Lewandowsky: Zeitschrift fur Klinische Medicin, 1899, Bandxxxvii., S. 535.

12 Camus and Gley: Comptes Rendus de la Société de Biologie, 1900,p. 210.

13 Blum: Pflüger’s Archiv, 1900, Band cv, S. 625.14 Ehrmann: Archiv für Experimentelle Pathologie und Pharma-

kologie, 1905, Band liii., S. 97.15 Melzer: Zentralblatt für Physiologie, 1904, Band xviii., S 317.

16 Abelous, Soulié, and Tougan: Comptes Rendus de la Société deBiologie, 1905, p. 533.

17 Elliott: The Action of Adrenalin, Journal of Physiology, 1905,vol. xxxii , p. 390.

18 Aubertin and Ambard : Bulletins et Mémoires de la SociétéMédicale des Hôpitaux, 1904, p. 175.

There is no information on the possible associationbetween hypertrophy of the posterior lobe of the pituitarybody and hypertension. These two known sources of a

pressor substance, suprarenal body and pituitary body,cannot be said to be the cause of the hypertension met within renal disease. The perusal of a p3per by Swale Vincentand Sheen 19 on the effect of intravenous injections ofextracts of animal tissues has aroused my interest in con-nexion with the subject of auto-intoxication, as I havedefined it for the purpose of these lectures, because thewriters appeared to have procured some evidence whichfavoured the idea that when once the parenchyma of anyparticular organ as a result of various pathological processesreached the circulation it was to be expected that changeswould take place in the degree of vascular tension. Theymade various preparations of organs of animals, includingdogs’, cats’, and rabbits’ tissues, and the procedure adoptedfor making "proteid extract" was the one followed inexperiments to be preently mentioned. A weighed quantityof fresh moist tissue was ground up with sand and to it wereadded three times as many cubic centimetres of salinesolution as there were grammes of the tissue ; the mixturewas filtered and always used at once.

Proteid extracts of brain tissue.-They found thatproteid extracts caused a rise, slight or marked, in five

experiments. The rise pictured shows a persistance for atleast 92 beats of the heart; in two experiments a falloccurred and in one injected with rabbit’s brain the fall wasa very pronounced one.

Proteid extracts of striped muscle tissue.—These usuallygave a double effect, a short rise lasting presumably aboutfour seconds, and a fall for more than 12 seconds. A purerise was noticed. once but never as marked as in the case ofnervous tissue.

Proteid extracts of kidney.-They noted most frequentlyand characterbtically the double effect, a rise and a fall.The next most frequent effect to occur was a pure rise ; onone occasion a fall occurred and on another no changeoccurred whatever. The rise figured by these workersfollowed just after the injection and lasted about 12 heartbeats. They found that, speaking generally, there is in thecase of kidney extracts, even more than with tho<e of muscleor nervous tissue, distinct evidence of a pressor effect.

Proteid extract of liver.-In the one experiment performedby these workers the proteid extract produced a distinct fall.

Proteid extraot of spleen.&mdash;A small but distinct fall wasproduced. A proteid extract of the intestine was tested onceand gave a fall.

In the perusal of this paper one is struck by the observationthat these workers have frequently to refer to the fact thatthe results obtained were not uniform and notably is this thecase with their observations on pressor effects, so that theysay the pressor effect seems to be less marked and of a morefleeting character and consequently more difficult to obtainthan the depressor effect; the pressor effect may be easilymissed unless the extracts are made in various ways and a

long series of experiments undertaken. Strength of extract,dose given, and stage in the experiment are all factors whichare capable of determining whether a pressor or depressoreffect is produced ; the best way to obtain the pressor sub-stance from any tissue is to extract the absolutely fresh tissuewith physiological saline solution and after thoroughtrituration and allowing the preparation to stand fora few minutes, to filter. A pressor or mixed effectshould be obtained from these preparations. They con-clude "that all glandular tissues and probably all animaltissues contain a pressor and depressor substance, theformer being usually extracted by saline solution at ordinarytemperatures, while the latter is extracted by boiling salinesolution, which either destroys (wholly or partly) the pressorsubstance or masks its effect by producing more of thedepressor substance." "The falls and rise of pressure areproduced by vaso-dilatation or vaso-constriction of variousvascular areas of the body." The writers were unable to saythat any particular extract had a specific local effect refer-able to the homologous organ. A depressor substance isdiscoverable in the liver, spleen, testes, pancreas, ovary, andlung. Other observers have found a depressor effect to begiven by the thyroid gland, thymus, and pituitary bodies ;even suprarenal extract when given in small doses exerts adepressor effect.

19 Swale Vincent and Sheen, Journal of Physiology, 1903, vol. xxix.,p. 242.

1304 DR. H. BATTY SHAW: AUTO-INTOXICATION, ETC.

In connexion with the subject of hypertension SwaleVincent and Sheen’s results are most important in thoseparticulars in which they are able to state that they haveestablished a pressor effect of tissues when injected into thecirculation. My own efforts at attempting to discovervariations in the effects following the injection of tissues invarious pathological conditions were followed merely by theobservation that in practically all cases (17 in number) therewas but one effect-namely, a depressor one ; occasionallythe injection of a preparation would produce a brief risemuch as does the simple injection of saline solution in somecases, though as a rule this latter solution generally causes a

slight fall. However, a careful re-perusal of Swale Vincentand Sheen’s paper impressed me that the organs removedfrom individuals dying from different diseases were not freshtissues, although keeping the bodies in an ice-chamber hadprevented their putrefaction. Moreover, suspicions were

aroused that possibly post-mortem softening might have soaffected the reactions of the fresh tissues that supposingany pressor substances had been present in the organs of thepatients who had died such active agent would have dis-appeared. At this stage I was very materially helped by Dr.

1305DR. H. BATTY SHAW: AUTO-INTOXICATION, ETC.

Schryver, who pointed out to me a certain period subsequentto the removal of tissues from animals in which the tissuesdo not undergo chemical change. An appeal, therefore, wasmade to the effects of fresh tissues removed from a cat andafter preparation injected into another.Mode of preparation.&mdash;An animal was killed under an

anaesthetic and with aseptic precautions the liver, the

kidneys, the brain, the spleen, &c., were removed. The

kidneys were stripped of their capsules, then split, and asmuch as possible of the pelvis and the neighbouring vesselswere removed ; the bile duct and gall-bladder were cut awayfrom the liver and all the organs were washed in sterilesaline solution. So much of each organ was weighed out in

100 C. The anaesthetic used was ether in every case andcare was taken without the aid of morphine or curari tosecure deep anaesthesia. The ether was administered througha cannula inserted in the trachea in the latter part of eachexperiment. The blood pressure was recorded from theright carotid artery. A cannula was tied into the rightfemoral vein for the purpose of injecting the extracts.The first series of experiments carried out in the above

way included those animals in which several different tissueextracts were injected into the same animal; the order ofinjection is given in Table IV. ; the series consisted of eightexperiments carried out on eight animals-Nos. 12, 22, 23,25, 29, 31, 32, and 33 A. No records of the experiments

TABLE IV.-SHOWING PRESSOR OR DEPRESSOR EFFECTS FOLLOWING INTRAVENOUS INJECTIONS OF EXTRACTS OFFRESH ORGANS.

In Experiment 29 reference is made to the effects of normal kidney and to sclerosed kidney. This interesting condition is comparable to thespecimens referred to in the beginning of the lecture in which one kidney was found to be atrophied as a result of atheroma of the renal artery,the other kidney being much larger than normal. In the case of the cat, the renal artery of the scarred organ was found to be much smallerthan that of the healthy kidney.

grammes and to it were added three times the number ofcubic centimetres of sterilised salt solution ; this was

then ground up with a small quantity of white sandwhich had been sterilised and washed in saline solu-tion. After the preparation was thoroughly macerated itwas pressed through fine meshed sieves, thus completing thedisintegration of the organ. The preparation was thencentrifugalised and filtered through coarse filter paper. Thefiltrate now took the form of a fine emulsion and showedmicroscopically many fine granules of varying size. Thepreparations were injected into other cats, as a rule fromwithin two to four hours, and in one case not for 12 hours,the preparation having been kept in an ice-box at from 80 to

Nos. 12 and 23 are given ; No. 12 was a curious example inwhich the animal failed to show any reaction-pressor ordepressor-on the injection of any tissue or of saline solutionalone. No. 23 was an example of an animal in whom therespiration was so irregular, quite apart from injection ofmaterial, that no attempt was made to carry out completeexperiments. There are therefore six experiments left forconsideration. The effects of injection of different organsupon the blood pressure have been tabulated and the analysisof the spleen and muscle effects shows that injection of spleengave a rise of pressure on three occasions of 18 millimetres,two millimetres, and three millimetres, lasting respectively45 seconds, 10 seconds, and 30 seconds ; a fall occurred in

1306 DR. J. H. TEACHER: PRIMARY INTESTINAL ANTHRAX IN MAN, ETC.

two cases of four millimetres, lasting from one to twoseconds, and of 6 millimetres, lasting four seconds. Injectionof muscle extract was practised twice ; in one there was amarked fall of 38 millimetres lasting four minutes 28seconds, and in the other a fall of only four millimetres,lasting one minute 55 seconds. The observations on thekidney, the liver, and the brain were more numerous and aretabulated according to whether they caused a rise or fall(Tables V. and VI.).

TABLE V.&mdash;Showing Rise of Pressure after Injection ofVarious Extracts.

TABLE VI.&mdash; Showing Fall of Pressure after Injeoting VariousExtracts.

In Table3 V. and VI. the heading "Maximum " means the highest orlowest maximum point the blood pressure reached respectively duringthe interval in which rise or fall occurred. The duration in Table IV. is

qualified in many cases by the words "at least" because it was neces-sary in these cases to stop the kvmograph and so economise tricingpaper in order to get the whole series on one tracing.

It is obvious that though other organs than the kidneyoccasionally show a rise of pressure on injection, yet therise is small and of short duration; whereas the kidneyeffect of a rise, though varying within considerable limits, isa striking feature, and the same may be said of the durationin which such rise takes place ; no other organ has beennoticed to have such an effect FO frequently. The liverand brain show a much greater tendency to cause a fallof blood pressure and even then such fall is generallyof very brief duration. One point to which it is neces-

sary to draw attention is that in none of these

experiments was the kidney extract injected first ;the injection always succeeded that of some other organ andit may be objected that it is possible that the rise of pressurefollowing the injection of renal extract is due to some inter-action of renal extract with some previous extract. More-over, it may be thought that the renal extract is of adifferent physical character and likely to cause a rise ofpressure from some mechanical effect dependent upon thegranules contained in the emulsion. As will be seen later,there is no reason to believe that either of these objectionsholds good. It is to be observed once again that theseanimals were simply under the influence of ether ; this wasso carefully administered that the respiration was maintainedregularly. In another experiment, 33B, with ether anes-thesia and artificial respiration, the vagi were cut ; an

injection of renal extract then produced the exceedinglysmall rise of only four or one millimetre, lasting one minute40 seconds and 25 seconds respectively. So far as this. oneexperiment is concerned it must be stated that the secondinjection of an extract has on other occasions shown lessmarked reaction than the first one. The slight rise, such asit is, merely suggests that the rise of pressure on injectingrenal extract is due to a peripheral effect whereby the arterialpressure is raised.

A CASE OF

PRIMARY INTESTINAL ANTHRAX IN MANSEPTIC&AElig;MIA; H&AElig;MORRHAGIC

LEPTO-MENINGITIS.1

BY JOHN H. TEACHER, M.D. GLASG., F.F.P.S. GLASG.,ASSISTANT TO PROFESSOR OF PATHOLOGY, UNIVERSITY OF

GLASGOW; ASSISTANT PATHOLOGIST AT THE WESTERNINFIRMARY, GLASGOW.

THE following case of anthrax is of interest from severalpoints of view. It appears to be an example of that form ofthe disease which is the most common in animals but therarest in man-viz., that in which infection occurs throughthe alimentary canal. The infection was extremely virulentand the course of the disease was correspondingly rapid, thewhole known duration of the illness being 20 hours. Therewas nothing in connexion with the occupation of the patientto suggest anthrax and the symptoms gave no clue to thenature of the disease. Until the h&aelig;morrhagic condition ofthe meninges was revealed at the post-mortem examinationanthrax was never suspected. Moreover, the case appears tohave been completely isolated and all investigations sub-

sequently undertaken have failed either to reveal the sourceof the mfection or to bring to light other cases of thedisease in man or animals in the neighbourhood of thepresent one.

Clinical history by Dr. ROBERT BELL.-A man, aged 36years, was admitted to Ward 12 of the Western Infirmary,Glasgow, at 11.15 P.M. on Jan. 31st, 1905, in a semi-consciousand delirious state. According to the account of his friendshe was to all appearance in perfect health until the morningof the day of his admission, when he rose with the intentionof going to work but returned to bed because he felt

giddy and had a headache. The headache he describedas a pain beginning behind and shooting over to the fore-head, while occasionally he complained of pain in the

region of his right ear and right eye. He remained inbed all day and took a little light food, and he

appeared to be not at all seriously ill. About 7 P.M., how-ever, his friends heard him give a cry and went to the bed-room, where they found him out of bed, very restless andexcited, and talking in an unintelligible manner. He wouldnot reply to any questions but would rise suddenly, go andsit down by the fire, holding his head and moaning, and thenas suddenly he would jump into his bed again and would liehuddled up. This restlessness and excitement he showed inan increasing degree up to the time of his admission. The

patient worked at the making of white lead in a paintmanufactory. The people with whom he lodged had knownhim for five years and he had been an exceptionally strongand healthy man. They stated that he had not been a heavydrinker but he occasionally had a bout of two or three days’duration, after which he would be steady for some weeks.When seen in the receiving room at 11.5 P.M. he was beingheld in a chair by three or four men so violent were hisstruggles. On admission to Ward 12 he seemed unconsciousbut if spoken to loudly he opened his eyes and looked about.If left to himself he lay huddled up with his legs and kneesdrawn tightly up and flexed upon the abdomen, his armsthrown across the chest, and his head bent with the chin onthe sternum. But if any attempt were made to move him orrouse him he struggled violently and occasionally gave a lowsighing moan. The pupils were moderately dilated andreacted sluggishly to light ; they were equal. The teethwere tightly closed and could not be opened. On the gumsthere seemed to be a suspicion of a blue line. Respirationwas easy and quiet, 24 per minute. The pulse was small,wiry, 90 per minute. The temperature was 98’ 40 F.

1 Communicated to the Glasgow Pathological and Clinical Societyin March, 1905.