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or Lane’s chronic intestinal stasis, and a minoritygroup who have an authentic chronic appendicitis. Thecause of the pain and tenderness in the first ormajority group is dragging and distension of a large,loose, dropped caecum. On exploration one may alsofind Lane’s ileal kink, an appendix looped up inretention bands (which ought not to be calledadhesions), extensive Jackson’s pericolic membrane,and general visceroptosis. The pain in such cases isdue to a combination of ptosis of the csecum andadhesions or bands about it, giving rise to kinking orto a concertina arrangement of the csecum andascending colon. Obviously it is useless to remove theappendix if the pain is due to such a cause, and hereis the main reason for the unsatisfactory surgery wehave just referred to.A careful history will generally help us to dis-

tinguish between this condition and true chronicappendicitis. The pain of mobile caecum is continuousday after day for weeks, months, or years ; now better,now worse, but seldom entirely absent. It is often(not always) relieved by recumbency, and especiallyby taking meals lying down. (This avoids the kinkingor concertina-deformation of the caecum, which occurswhen that organ prolapses into the pelvis but is heldup here and there by bands. Taking food leads tocascal peristalsis’, which is painful under such circum-stances.) The costal angle is narrow and often thekidney is movable. This type of patient is sufferingfrom the virginal form of visceroptosis, not thematernal, so one must not expect to see marked saggingof the lower anterior abdominal wall. Very valuableevidence will be given by a barium meal, showinggeneral visceroptosis, a distended caecum, perhapsprolapsed and tied by bands, and marked delay in itsemptying time.

In genuine chronic appendicitis, on the otherhand, the usual history is of periods of pain and periodsof freedom from pain. The patient may be able tocount the attacks, although there may never havebeen any rise of temperature. The above-mentionedsigns of visceroptosis are absent, and recumbency doesnot give relief. Sometimes, it is true, one sees a patientwith never-ceasing pain due to the appendix, com-pletely and permanently cured by removal thereof,but it requires considerable circumspection to pickthese out from amongst the merely caecal cases.

Patients suffering from pain of caecal origin oughtnot to be operated on until good trial has been madeof a Curtis belt, liquid paraffin, recumbency for meals,a diet rich in vitamins, &c. If one is driven to operate,or finds the condition during an exploration for appen-dicitis, my practice, in addition to removing theappendix, is to perform a excoplication, not so muchto narrow the caecum as to shorten it, and the resultshave been very good. Others perform Waugh’soperation. In a very few very extreme cases I do ahemicolectomy and have had a few failures and anumber of striking and lasting successes. Somesurgeons excuse the recurrence of pains after removalof the " chronic " appendix by alleging that adhesionshave formed. This must be very rare. In my experi-ence, if the diagnosis of chronic appendicitis is onlymade in accordance with the principles just described,there will be few if any patients coming back again forrecurrent pains after removal of the organ.

LATENT APPENDICITIS.

Chronic inflammation of the appendix may beresponsible for symptoms quite different from thosealready described. These cases of latent appendicitisfall into three groups at least : (1) Irregular attacksof fever, perhaps vomiting, and vague abdominalpains in children and boys and girls of school age, butwith no signs localised in the right iliac fossa;(2) symptoms like those of gastric or duodenal ulcer,but usually atypical in some respect (= appendiculargastralgia) ; (3) profuse haematemesis with or withoutdyspeptic symptoms, associated with a small atrophicimpervious appendix.

(To be concluded.)

THE BASAL METABOLIC RATE:ITS DETERMINATION AND INTERPRETATION.

BY HENRY F. MOORE, M.D., D.Sc.,VISITING PHYSICIAN, MATER MISERICORDIÆ HOSPITAL, DUBLIN ;

FORMERLY ASSISTANT, HOSPITAL OF THE ROCKEFELLERINSTITUTE FOR MEDICAL RESEARCH, NEW YORK.

(From the Wards and Metabolism Laboratory of theMater Misericordiœ Hospital.)

IN his book, " The Science of Nutrition," Lusklsays: " In each mammal there is a basal metabolism."By the term "basal metabolism" or "basal metabolicrate " is meant the minimal heat production of anorganism, measured from 12 to 18 hours after theingestion of food (post-absorption state) and with theorganism at complete muscular rest in a comfortablywarm environment. This minimal heat productionmay be determined directly by actual measurement bymeans of a calorimeter, or indirectly by calculating theheat production from determination of the amountof oxygen used within the organism and the corre-sponding amount of carbon dioxide produced, togetherwith the total nitrogen eliminated.

Francis G. Benedict2 states that the level of vitalactivity may be inferred from the amount of heatproduced ; whilst heat is the end-result of glandular-and muscular activity, oxidative processes are

essential factors in these transformations. Thus, theintake of oxygen is essential to combustion, while thproduction of CO2 makes up a very large part of thetotal oxidative processes of the body. Therefore, ifone can measure accurately the carbon dioxideproduced, or, better still, the oxygen consumed, avery close estimate of the total heat production, andconsequently of the end-results of glandular andmuscular activity, may be secured. Thus, by deter-mining the oxygen consumption under suitableconditions in a given time the basal metabolic rate maybe calculated.

THE BASAL METABOLIC RATE IN RELATION TOTHYROID DISEASE.

’ The essential function of the thyroid gland is theelaboration and delivery to the organism of thyroxin,a substance which was isolated in crystalline form in1915 by Kendall. According to Plummer, thefollowing statements hold true : (a) Thyroxin isactive directly or indirectly in the cells throughout thebody and, acting as a catalyst, it hastens the rate offormation of a quantum of potential energy availablefor transformation on excitation of the cell;(b) hyperthyroidism is the physiological or patho-logical status of an individual, otherwise normal, whenthe thyroxin in the tissues is sufficiently increased tohold the basal metabolism above normal ; (c) all thephenomena in pure hyperthyroidism are those thatattend a sustained elevation of the basal metabolismabove normal; (d) the status of the hyperfunctioningadenomatous goitre is the result of pure hyper-thyroidism, while that of exophthalmic goitre is notaccounted for by a pure hyperthyroidism (possiblyhere the thyroxin formed is chemically different in aslight way from normal thyroxin) ; (e) adequateintravenous administration of thyroxin to thyroidlesspatients, who invariably have a low basal metabolicrate, always restores the basal metabolic rate tonormal; (f) the average daily exhaustion of thyroxinby the tissues is from. 0-75 to 1 mg.Boothby5 states that by the term hyperthyroidism

is meant the clinical syndrome resulting from theaction in the body of an excess of thyroxin. From12-14 mg. of active thyroxin must be present in thebody to maintain the basal metabolic rate at the

normal level; excess of thyroxin in the organismincreases the rate.A decrease of the basal metabolic rate is charac-

teristic of myxoedema or cretinism, and is due to theinability of the thyroid gland to furnish sufficientthyroxin to the body.

’

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Thus, it is seen that the determination of thebasal metabolic rate may be of significance inthe study of disease of the thyroid gland. Thepossible increased basal metabolic rate in activeacromegaly and the decreased rate in hypo-pituitarism suggest that the alteration in theactivity of the pituitary gland may change the-metabolic rate, but there is little evidence that thesecretion of any part of the pituitary gland is concernedwith the normal rate of cellular combustion in thesense that its secretion acts, like thyroxin, as a

calorigenic agent. There are certain other diseases inwhich an increased basal metabolic rate is occasionallyobserved--e.g., severe anaemias and leukaemias ; thecause of the increased metabolism in these instances isnot known. Du Bois6 has shown that increase ofthe basal metabolic rate in fevers follows Van’t Hoff’slaw ot the velocity of chemical reactions with tempera-ture change-i.e., the basal metabolic rate is aboutdoubled for an increase of temperature of 10° C. Itis intiesting to note, in passing, that in 1919KendaU stated that 33 g. of thyroxin had beenseparated from 6550 lb. of fresh thyroid material.Thyroxin is stated to be 4-5-6-tri-iodo-2-oxybeta-indole-propionic acid ; it is closely related totryptophane ; it is a white crystallisable substance.and heat-stable. 8

METHODS OF ESTIMATING THE BASAL METABOLICRATE.

The methods available for the estimation of thebasal metabolic rate fall under two main categories :-

1. Direct Calorimetry.-The heat produced in themetabolic processes is determined in a respirationcalorimeter chamber. The apparatus needed is Iextremely expensive and complicated, and necessitatesa number of highly-trained technicians. This methodis altogether outside the resources of hospitals, and itis used only in a few institutions especially equippedfor research on metabolism.

2. Indirect Calorimetry.-Here either the oxygen.absorbed or the carbon dioxide liberated in a giventime, or both, are measured. From these figures therespiratory quotient can be calculated, and if thenitrogen eliminated in the urine is estimated at thesame time it is possible to apportion the oxygen used forthe burning of protein, carbohydrate, and fat. Thedetermination of the respiratory quotient and nitrogenelimination are, generally speaking, not necessary inclinical work. " The validity of the method has beenestablished beyond a doubt by the simultaneousmeasurement of heat by physical means, and of thegas exchange in a respiration calorimeter."9 9

There are two chief methods of indirect calori-metry :-

1. The Open Circuit Method.-The external air is breathedand the expired air trapped in a spirometer bell or bag,from which samples can be removed for analysis, and theiroxygen and carbon dioxide content determined. The.disadvantages of the use of this method in clinical medicineare that it is time-consuming, that the apparatus may becomparatively expensive, and that gas analyses are required,the technique of which is not sufficiently simple for general<clinical use.

2. The Closed Circuit Method.-Principle : F. G. Benedictof Boston 10 has developed a portable respiration apparatuswhich measures the oxygen consumption of human beingsdirectly, accurately, and rapidly. A relatively simpletechnique for the measurement of the oxygen consumptionof man has been evolved which necessitates neither largerespiration chambers, complicated valves, weighings, norgas analyses ; this is based on the observation that when asubject breathes pure oxygen the amount of oxygen taken’up by the blood and used is the same as when ordinaryair is inspired. This apparatus measures the oxygen only,for it has been shown that in ordinary work the oxygen.consumption is of prime significance in the vast majorityof pathological cases. Carpenter and Emmes make the-statement that when the measurement of basal meta-bolism is desired, it is waste of time to attempt any othermeasurement than that of oxygen consumption supple-mented by the controls they have recommended." Theseobservers with Hendry 11 state that when the oxygen

consumption alone is desired the Benedict apparatus is thebest apparatus for short period measurements. Again,where one gas is measured the absorption of oxygen is lessaffected by abnormalities of respiration than is the produc-tion of carbon dioxide.

In the original apparatus and modifications anelectric fan (impeller) was placed within the spirometerbell in order to drive the gases within the closedcircuit through a soda-lime container so that thecarbon dioxide might be absorbed and the gas sent inrespirable condition to the mouth of the patient. Thiselectric impeller is apt to get out of order, to heatthe circuit at times, and its noise is apt to disturbthe patient ; it is omitted in the Roth-Benpdictapparatus 12 and the original electric impeller andface-mask are replaced by simple rubber valvesand a mouth-piece.

The Roth-Benedict Apparatus.The Roth-Benedict apparatus consists of a spirometer

bell, cylindrical in shape (bearing a thermometer at theupper closed end), accurately counterpoised over a pulley

and suspended over a

FIG. 1.-Diagram of the Roth- double - walled cylinder

Benedict Apparatus zvith closed below, the space

Benedict Apparatus with between the vertical wallsKymograph Attachment. of which cylinder bemg

G. filled with a water seal(see Fig. 1). The spaceenclosed between the in-verted bell and the innerchamber is filled withoxygen over a soda-limecontainer and the oxygenis in communicationthrough two flexiblerubber tubes of about3-5 cm. diameter with therespiratory mouth-piece inthe patient’s mouth ; theflange of the mouth-piecefits between the lips and teeth, and the tonguesrest between the teeth.One of the tubes (theexpiratory tube) carriesthe expired air througha chamber containingWilson soda-lime placedwithin the lower chamberso that the C02is absorbedbefore the expired gasesreach the spirometer bellabove. The expiratory

A, spirometer bell; B, water seal; C, soda-lime container ;D, expiratory valve ; E, inspiratory valve in its housing ;F, mouth-piece ; G, pulley ; H, counterpoise weight, pointer,and kymograph pen-writing tracing; K, time-marker ;L, kymograph ; T, thermometer.

valve (which shuts at inspiration) is placed on top of thesoda-lime chamber, and the inspiratory valve (whichshuts on expiration) is situated in a special housing atthe end of the inspiratory tube below the body of theapparatus. In this way, when the nose is closed with anose-clip and the patient connected up with the apparatus,he expires into the spirometer chamber (the spirometer bellrising) through soda-lime where the CO2 is absorbed, and heinspires pure oxygen from the bell (the bell falling) with aminimum of frictional resistance. Thus, the oxygen con-sumed over a given time can be measured accurately by ascale adjacent to the counterpoise weight which carries apointer running on the scale-the pointer falls and rises asthe bell rises and falls ; or, if a pen is attached to the weightor pointer and allowed to write on a revolving drum witha suitable time-marker (Roth) the test can be recordedand the oxygen consumption measured graphically.13 Thevolume of the oxygen consumed in a given time is thencorrected to normal temperature, pressure, and for relativehumidity (80 per cent.) according to the laws of Charlesor Gay-Lussac, Boyle and Dalton. The Roth-Benedictapparatus is used by the present writer. Prof. Krogh of

25 221

Copenhagen has also independently devised a clinicalapparatus similar in principle to the Roth-Benedict.* *

Having determined the oxygen consumption, thismust be compared with standards of oxygen consump-tion of normal persons of the same size, shape, age,and sex, in order to estimate whether the oxidationprocesses of the organism, and therefore the basalmetabolic rate, are greater or less than normal.Rubner 14 suggested that the heat production of anindividual was proportional to his surface area, andE. F. and D. Du Bois16 devised a linear formulabased on height and weight, after the most carefulmeasurements, whereby the body surface could becalculated with an average error of under 2 per cent.Later D. Du Bois devised a simple though slightlyless accurate (&plusmn;5 per cent.) formula which is :&mdash;

Surface area=W 0.425 HO-725 x 71-84,where W = weight in kilogrammes and H = height incentimetres.

On the basis of this formula Du Bois then constructeda height-weight chart by means of which the surfacearea could be estimated at a glance, and, by using sucha chart in conjunction with his standards of normalbasal metabolism for age and sex, Du Bois showed thatthe metabolism of normal adults per square metre ofbody surface could be predicted with an accuracyof 10 per cent. The height-weight chart of Boothbyand Sandiford&dagger; is convenient to use; a straight-edgejoining the weight and height figures cuts thecentre line at the figure for body surface. Benedict 16criticised this method on the ground that the heatoutput of the body at rest does not depend on Newton’slaw of cooling and is therefore not proportional tobody surface ; consequently Harris and Benedict 17compiled standards bahed on weight, age, sex, andheight, but the results obtained by using both sets ofstandards do not differ very markedly (6-5 per cent.higher by Harris-Benedict method). Other standardswere devised by Dreyer,18 and Benedict and Talbot 19have compiled standards for boys and girls based onweight, and Benedict and Hendry 2" for girls at theage of puberty based on age and weight. Boothby andSandiford 21 conclude that the Aub-Du Bois standardsgive the best method available at present for predictingthe normal heat production. The best standards forboys and girls ranging in weight from 2-5 to 38 kg.seem to be those of Benedict and Talbot (see Table I).

TABLE I.-Basal Heat Production Standards.22

(A) Benedict-Talbot Standards for Boys and Girls.Calories per kilogramme per hour predicted from body-weight.

(a) = Figures based on general trend of table. Not in original. I* The Roth-Benedict apparatus may be obtained from Mr.

Warren E. Collins, 584, Huntington Avenue, Boston, Mass.,U.S.A., and it and the Krogh form from H. E. Kendrick,3, Morley-avenue, Higham’s Park, London, E. 4. The SanbornCompany have a modification on the market also obtainablethrough Mr. Kendrick.

+ Given in the author’s reprints.

(C) Benedict-Hendry-Baker(B) Aub-Du Bois Standards. Standards for Girls 12 toCal. per sq.m. of body surface 17 years of age.

(height-weight formula) Cal. per kilogramme per hour

-

per hour. predicted from age.

(D) Harris-Benedict Standard Formulas.For Males (applicable to boys back to 10 kilos. in weight).

’ H = 66-473 + 13’752 w + 5-003 s- 6-755 a.For Women (for ages not under 21 years).

H = 655-096 + 9-563 w + 1-850 s - 4-676 a.

H = heat production, cal. per 24 hrs. w = weight in kilos.s = stature in centimetres. a = age in years. -

Graphic Method (Roth, see Figs. 2, 3, and 4).-The mouth-piece and conducting tubes having been cleansed andsterilised, the apparatus is assembled. The sealing chamberis filled with water to within a few inches of the top. Theabsorbing chamber is filled with suitable granular soda-lime(Wilson brand is recommended). The charge of soda-limecan usually be used for several tests, and should be changedwhen it ceases completely to absorb CO2, as shown bybubbling a sample of the air in the spirometer at the end of atest through baryta water by means of a tube connected to asmall stopcock placed in the bottom of the respirationchamber. A test thus showing unabsorbed CO2 should bediscarded. After filling the soda-lime container its cover issealed with a rubber band, and the rubber flutter valve onthe cover is examined to see that the lateral slits comebarely in contact with each other. This may be regulated by

Case H. B.-Female, aged 44. P., 86 ; T., 98-5&deg; F.; R., 20 (B).P., 73; T., 98.6&deg; ; R., 20 (E). Spiro. T., 11.5&deg; C. (B),11’50 C. (E). Wt., 151 lb. = 68-6 kg. ; Ht., 63 in. Bar.,754 mm. Hg. 0 line = cals. per hr. = 184 -106 = 78mm. ; corrected cals. per hr. = 78 x 0-952 = 74’2 (N.T.P.).Area body surface - 2-02 sq. m. (= 2) ; cals. per sq. m.per hr. = 36-7 (= 37). Average normal cals. per sq. m.

, per her. 36 (Aub and Du Bois). B.M.R.= -2.7 %(= -3%).

B = just before test. E = just after test.

drawing the valve more or less over the metal tube. Ifproperly adjusted the rubber valves are almost noiseless andnever stick if clean. The soda-lime container is then tightlyscrewed in position within the inner chamber. The inspira-tory valve is also examined prior to the test. Any water ofcondensation that collects in the lower expiratory tubeshould be drained away after the test as necessity for sodoing arises. The respiration chamber is filled to therequired degree with oxygen with a cork blocking themouth-piece, and the apparatus is tested for leaks byplacing a weight on the spirometer bell and noting whetherthe pointer rises after a few moments. The operator shouldhimself use the apparatus before the test for a few moments-the connexions can be cleansed before use with the patientor a fresh set used. The fasting (15 hours) patient isi eclining and resting comfortably, fully relaxed, for at least

222

half an hour on the couch beside the apparatus before thetest; he should not smoke on the morning of the test;he is protected from the cold or visitors, and kept as quiet aspossible. He is instructed beforehand as to the nature andrequirements of the test in order to gain his confidence andensure cooperation. His pulse and respiration rates arenoted several times during the half-hour rest and his tempera-ture taken. When all is ready the cork is removed, and themouth-piece is inserted in the patient’s mouth with the twolugs between the teeth and the oral flange between the lips

in the measurements. It is better to base thecalculation on a short undisturbed period of only fouror five minutes than on a larger one which includesvitiated sections. For example, consciousness of thepatient of his own respirations, often intensified byhis effort to breathe correctly, may cause the degree ofexpansion of the lungs to vary considerably ; such asource of error will generally be revealed by thekymograph, but might readily otherwise pass

undetected and introduce a considerableerror.

_ _

Roth states that further advantages of hisgraphic method are as follow :-

" It simplifies the technique. It reduces to aminimum the necessary procedures. There are nospirometer readings to be made. Stop-watches canbe dispensed with. The kymograph automaticallyrecords the time, the oxygen consumption, and, toa large extent as well, the working condition of theapparatus and the behaviour of the subject. Theaverage respiration count per minute is most con-veniently obtained from the tracing. One operatoronly is needed to supervise the entire operation,including the counting of the pulse, to observe thespirometer temperature and the barometric pressure,while at the same time an occasional glance atthe kymograph keeps him informed as to whetherthe test is progressing under desirable conditions.The computations, as ordinarily carried out, arenaturally reduced if based on the graph which,

Aged 42 yrs. P., 70 ; T., 97’40 F. ; R., 20. Spiro. T. at B -.10&deg; C.; at E = 11&deg; C. (10’50 C. = av.). Bar., 771 mm. Hg ; Ht. =66 in. ; Wt. = 168 lb. O2line = cals. perhr. = 143 -73 = 70 mm. ;corrected cals. per hr. = 70 x 0.977 = 68-39 (= 68-4). Bodysurface = 1-85 sq. m. ; cals. per sq. m. per hr. = 36-97 (= 37).Average normal cals. per sq. m. per hr. a 38-5 (Aub and Du Bois).B.M.R. -4-16%= -4%.

It O2line =70+4, B.M.R. = + 1. If 0 2 line = 70 -4, B.M.R. = -9.

furthermore, allows the full advantages presentedin the considerably simplified system of calculationpresented."

It is to be noted that direct readings fromthe scale when no graph is used make the testmore laborious.

and the nose-clip is applied. Then, after a few minutes, thekymograph is brought into contact with the recording pens,and the respiratory movements of the bell are recorded abovethe time tracing on the paper of the revolving drum. Theupward tendency of the tracing denotes oxygen consumption.The spirometer temperature is noted at the beginning andend of the tracing, and a tracing of about ten minutes’duration is recorded. After a rest the test can be repeatedif desired.

Roth states that a kymograph record of themovements of the spirometer bell taken during atest simultaneously with a graphic time record (seeFigs. 2 to 4) is the most accurate basis for themeasurement of the oxygen

The object desired is the determination ofthe percentage increase or decrease of the metabolicrate of the subject as compared with the acceptedaverage normal standards which are expressed (DuBois) in terms of calories used per square metre ofbody surface per hour. In clinical work the calorieselaborated by the patient are calculated from theamount of oxygen he has absorbed during the timeof the test ; one litre of oxygen absorbed = 4-825calories ; this figure varies slightly according tothe proportion of fats, proteins, and carbohydratesoxidised by the subject, but in practical clinical teststhe average calculated calorific value of oxygen is

consumption or me subjectbv the method of indirectcalorimetry. Further, notonly is a permanent recordof the test secured, but theoxygen consumption can bemore easily and accuratelymeasured by the graphicmethod than by the methodof direct readings indicatedby the moving pointeragainst the millimetre scale,especially with subjects whobreathe irregularly. Again,no disturbance of anysignificance for the inter-pretation of the test canoccur to the patient duringthe test without affectingthe respiration in a mannerreadily detected from thetracing. Not infrequently,also, the test is started

B.ged37yrs. Wt., 51 kg.; Ht., 169 em. ; Bar. = 768 mm. Hg. Temp. of spiro. 14&deg; C. Temp.of patient: Before, 97 F.; after, 97.40. Pulse: Before, 84; after, 82. Respir.:Before, 24; after,, 22. 0 2 line = 157 - 40-5 = 117 mm. = cals. per hr. ; corrected =117 x 0-941 = 101 cals. per hr. Body surface = 1-57 sq. m. ; cals. per sq. m. per hr. =64-3. Average normal cals. per sq. m. per hr. (Du Bois) = 36-5. R.M.R. = + 76 per cent.

returned to the basal condition which a 30-minutepreliminary rest period is intended to ensure, butwhich is apt to be more or less disturbed in theprocess of starting the test; if, as a result, themetabolic rate has been temporarily increased therespiration curve will readily show it, and any portionof the tracing which does not represent the probablebasal metabolic rate of the subject can be disregarded

oxygen-assuming 0.82 as the average respiratoryquotient.For very accurate measurement of the heat produc-

tion the measurement of both respiratory gases isnecessary, because the heat value of the unit quantityof oxygen or carbon dioxide varies according to thenature of the foodstuff oxidised. When fat is burned

223

the heat value of one litre of oxygen is 4-686 calories ; when carbohydrate is oxidised the heat value is 5-047 and the protein value is 4-485. Thus, the heat generated as calculated from oxygen consumption orcarbon-dioxide production varies with the non-proteinrespiratory quotient which normally lies between0-71 for fat and 1-0 for carbohydrate, and to determine the respiratory quotient both gases must be measured. The non-protein respiratory quotient is derived by calculation from a knowledge of the urinary nitrogenexcretion over a given period.The actual oxygen consumption is determined from

the fall in the spirometer bell in millimetres as

indicated by the pointer on the scale or the rise of thetracing. To shorten the calculation (Roth) a sectionof the tracing of one-tenth of an hour (six minutes) istaken and the bell is constructed with a volume of20-73 c.cm. per mm. of its height. Thus, each milli-metre fall of the bell or rise of the tracing (rise of theO2 line) in a six-minute period represents one calorieper hour :-

1 mm. in 6 minutes = 20’73 c.cm.. ’. O2 = 207-3 c.cm. = 0-2073 litre per hour.

0-2073 x 4-825 = 1 calorie per hour.

The consumption of oxygen is measured by drawingan average line along the base of the respiration curve,dropping two perpendiculars to the base line at thebeginning and end of the six minutes period andmeasuring the height of the perpendiculars; thedifference in mm. represents calories per hour. Thisfigure, which represents the volume of oxygen usedby the subject in six minutes, is next corrected for thespirometer temperature, barometric pressure, andhumidity (80 per cent., using Wilson soda-lime) bymultiplying by a factor obtained from a table.22tThe average spirometer temperature is taken fromtemperature readings recorded at the beginning andend of the test. A change in temperature of lessthan 1&deg; C. can be ignored, but if a rise of more than1&deg; C. is noted allowance is made by adding for eachdegree centigrade of rise of temperature 0 -5 millimetreto the total rise of the O2 line in six minutes.The next step is the calculation of the calories

produced per square metre of body surface ; thebody-surface area is read directly from the Boothbyand Sandiford chart 23 by laying a straight-edgeacross the figure joining the weight in kilogrammesand the height in centimetres. The figure representingcalories per square metre of body surface per hour iscompared with the average normal number of caloriesper square metre per hour obtained from the tablesof normal standards (Table 1.), and the percentageincrease or decrease noted. The latter is given as thebasal metabolic rate.The normal zone of basal metabolism for male

adults and non-pregnant women is usually taken tolie between &plusmn; 10 per cent., but with ambulatorypatients it may be taken to lie between 15 per cent.The basal metabolism of children probably varieswithin a still wider range.

CONDITIONS NECESSARY FOR A SUCCESSFUL TEST.

The following conditions on the part of the patientare necessary for a successful test: (a) Completecooperation and absence of apprehension concerningthe test-the test is often 10 per cent. higher than itshould be when the patient is nervous and appre-hensive ; (b) the test should be performed in themorning with the patient in the post-absorption state-that is, having had a light supper the previousnight and no food for at least 14 hours prior to thetest ; (c) muscular relaxation &sect; ; (d) a preliminaryrest period of at least 30 minutes in a comfortablywarm room with the subject in the reclining positionon the test couch ; (e) body temperature within normallimits; (f) the respirations should be reasonably

t Given in the author’s reprints.&sect; Grafe studied various forms of tremor and concluded that

the metabolism is increased only if the tremors are very markedand that emotion increases the metabolic rate (quoted byDu Bois 33).

regular during the test, but irregularity of therespiration rhythm or depth is more apt to affect theCO2 excretion than the oxygen absorption.

Interpretation.The test should be interpreted in relation to the

history, clinical condition, and physical examinationof the patient and it cannot and should not beevaluated by itself alone. McCann writes:-"If the basal metabolism is determined by the most

accurate technique, under rigidly controlled conditions, adeviation from the average normal can be properly inter-preted only in the light of the most thorough and painstakingclinical study of the case. In the last analysis a diagnosismust rest upon the clinical observations. As an unbiasedobjective method of evaluating the results of therapeuticmeasures in thyroid disease, especially as a means of con-trolling the treatment of hypothyroidism, basal metabolismdeterminations are invaluable.... Metabolism determina-tions are unsurpassed as an objective means of measuringthe severity of hyperthyroidism or hypothyroidism andthe response to various forms of treatment."

Du Bois 23 writes :-" There seems to be a striking unanimity of opinion that

the level of the basal metabolism is the best guide to the .

activity of the thyroid gland. This has a sound physiologicaland clinical basis. We must remembar, however, that weare dealing with a laboratory test, and that it must not beaccepted blindly. There are certain limitations which shouldbe emphasised at this point. The technic is difficult, anderrors of 10 or 20 per’cent. may be made, especially bybeginners. Even in the best hands there is a possibleerror of 2 or 3 per cent. In addition to this there are ratherwide fluctuations in the dailv metabolism of certain indi-viduals. The first few tests with a thyroid patient may be10 or 20 per cent. too high. Some normal individualsconsistently show rates 10 to 15 per cent. or even moreabove or below the normal. The chances are that thesevarious sources of error will partially neutralise each other,but if they all happen to fall in the same direction the resultwill be far from the truth.

" In every disease there is a tendency to variation from thetypical which occurs in certain individuals, and there are fewhard-and-fast rules in diagnosis. It is very seldom that weshould allow any single symptom or laboratory test tooutweigh a mass of evidence. A slavish adherence to thebasal metabolism test as an index of diagnosis may leadthe physician to trouble, first because the test does not.always give the true basal metabolism, and second becauseeven the true basal metabolism is not always the indicationof the correct diagnosis. God forbid that we make ourdiagnoses by machinery ! "

The basal metabolism may be notably increased infevers, hyperthyroidism (Graves’s disease, thyrotoxicadenomata, and some cases of malignant tumour ofthe thyroid and thyroiditis, overdose of thyroidsubstance or thyroxin), many cases of severe ansemias,many cases of chronic leukaemias, after food ingestion,from muscular work and in some cases of hyper-pituitarism. The administration of insulin andsuprarenal extract usually causes some increase in thebasal metabolic rate. The basal metabolic rate maybe notably decreased below the normal limits inhypothyroidism, in the clinical conditions myx&oelig;demaand cretinism, in traumatic shock, and in chronicinanition.

It is in diseases of the thyroid gland that thedetermination of the basal metabolic rate is of mostvalue in clinical medicine. From an analysis of over6000 thyroid cases Boothby and Sandiford 24 statethat 98 per cent. of cases of exophthalmic goitre havea basal metabolic rate of over 10 per cent. above theaverage normal values of Du Bois and Aub, andonly 7 per cent. were within the limits of &plusmn; 15 percent. ; 56 per cent. of cases of thyroid adenomatashowed evidences of hyperthyroidism with a basalmetabolic rate of more than 10 per cent. above normal ;the vast majority of colloid goitre cases showed anormal rate and a few showed an increase up to20 per cent. above normal.According to Kessel, et alia,25 cases which show

the "sympathomimetic" symptoms of Graves’ssyndrome (tachycardia, tremor, exophthalmos,asthenia, diarrhoea, sweating) without increase ofthe basal metabolic rate and without goitre are

to be considered not cases of hyperthyroidism but

224

of "autonomic imbalance." These cases are called" border-line " cases by Means.

DIAGNOSTIC VALUE OF BASAL METABOLIC RATE.The use of the determination of the basal metabolic

rate in the diagnosis of thyroid disease is stated asfollows by Means and Burgess2g :-

" Patients with an outspoken picture of hyperthyroidisminvariably show increased metabolism, and those withdefinite clinical pictures of hypothyroidism invariably showdecreased metabolism. Those with goitres, but no signs orsymptoms of abnormal thyroid function, for the most partshow normal metabolism." By inference from the indirect evidence we believe that

in these border-line thyroid cases, provided that in thefirst place a true basal rate is secured, and, provided thatcertain well-recognised causes for increased metabolism,such as fevers, acromegaly, leukaemia, and severe anaemia,are excluded, the finding of increased basal metabolicrate is strong presumptive evidence of hyperthyroidism.In a similar way, provided that such conditions as starva-tion, hypopituitarism, and hyposuprarenalism are excluded,a low metabolic rate is strong presumptive evidence ofhypothyroidism.

" To that extent, then, the metabolism test is distinctlyuseful in differential diagnosis. Like all other laboratory

tests it should only be interpreted with due regard to allother clinical and laboratory findings, and with due regardfor its limitations and pitfalls."From our own limited experience and from a study

of the literature on the subject we have concludedthat the test gives useful information for estimatingthe degree of thyroid deficiency, of thyrotoxicosisand the results of treatment, that it gives considerableinformation in the differential diagnosis of mild anddoubtful cases suspected to have hyper- or hypo-thyroidism, but that it is not of great value inthe diagnosis of frank cases of hyperthyroidism,myxoedema, or cretinism.A summary of illustrative cases and cases of

special interest are given in tabular form (Tables II.and III.).

TABLE II.&mdash;Summary of Illustrative Cases.

In addition to the cases studied from my ownwards I desire to thank my medical and surgicalcolleagues of my own and other hospitals for sendingcases for the test.

TABLE III.&mdash;Summary of Additional Cases of Special Interest.

per cent.CASE 1. Male, aged 18. Non-toxic parenchymatous

per cenL. . i

goitre with colloid cysts .... +12After 0’2 mg. thyroxin by mouth for ten days showed

fine tremor, nervousness, moist skin, and pulse of92 to 96 per minute .......... +41

CASE 2.-Female, aged 17. Tremor; tachycardia(120) ; thyroid appears "full" ; slight lag of upperlid; no exophthalmos; heart normal .... +19

CASE 3.-Male, aged 30. Slight uniform enlargementof thyroid, tires easily, some palpitation on effort ;some tremor; moist skin ; heart, lungs, and abdo-minal organs normal; constipation; polyuria, urineand kidneys normal; blood-sugar normal; loss ofweight; rather " nervous " ; no hyperthyroid eyesigns. Tendon reflexes brisk. B.P. 120/80 ; pulse70 at rest, 90 to 100 after moderate exertion--doesnot return to normal rate for several minutes.Apparently, a " border-line " case-" autonomicimbalance " ............ +0-5

normalCASE 4.-Male, aged 22. Uniform thyroid enlargement, tremor on excitement, occasional diarrhoea, moistskin; pulse averages 80, but goes up to 90 onslight exertion ; slight exophthalmos (?); moistcyanotic hands. Clinically very mild thyro-toxicosis (perhaps in remission) or

" autonomicimbalance " ............ &mdash; 6

CASE 5.-Female, aged 47. Exophthalmic goitre.Frank case of thyrotoxicosis. Her local physicianhad been giving her thyroid substance by mouthfor three weeks.. +133

After stopping thyroid medication and rest for tendays.............. +47

CASE 6.-Male, aged 35. Exophthalmic goitre ; frankcase, heart enlarged ; marked eye signs.... +61

After nine months’ treatment (rest, general hygiene,X ray) is clinically much improved and able towork but still has thyroid swelling; exophthalmosslightly improved .......... +18

CASE 7.-Female, aged 39. Frank case of Graves’sdisease ..... +97

After rest in bed for two weeks and a few X rayexposures ............ +64

After a further 13 days’ rest in bed and 30 minims ofliq. iodi co. (U.S.P.) by mouth per day, patient wasclinically much improved ; exophthalmos greatlyreduced (see below (a) ) ..., .... +48

per cent.CASE 8.-Female, aged 46. Frank case of Graves’s

disease. Marked exophthalmos, moderate thyroidenlargement; slight tremor. Moist skin and saysshe perspires too easily; pulse averages 86, nodiarrhoea or constipation and no menstrual dis-turbance. Clinically mild thyrotoxicosis .... +68

After 15 days of liq. iodi co., m xv. t.i.d., bymouth, and partial rest in bed. Clinically muchimproved; exophthalmos only slight and tremorvery slight (see below (a) ) ........ +1

CASE 9.-Male, aged 23. Clinically, prior to tests,looked on as an " effort syndrome or " autonomicimbalance case. Tires easily; palpitation on +32 (b)exertion ; pulse at rest averages 80, but goes up to110 or 120 on moderate exercise and does notreturn to normal rate for several minutes after- +56 (b)wards; can feel his heart beating forcibly onslight exertion ; hands and feet cyanotic and showloss of tone of skin vessels ; marked tremor of +41 (b)hands and legs, especially on left side; periodicdiarrhoea; can concentrate on mental work forshort periods only ; no abnormal thyroid enlarge- +65 (b)ment and no accessory thyroids discovered (thyroidappeared slightly full at last examination) ; blood-sugar normal; very " nervous." Cerebro-spinal +77 (b)nervous system normal except for brisk tendonreflexes. Had no treatment during the ten monthsof observation except sedatives and change to the +58 (b)country. No evidence of thymus enlargement byX rays or otherwise. The case is evidently one ofhyperthyroidism........... +58 (b)

After 30 minims of Lugol’s solution by mouth for 25days (see below (a) ) ; improved...... +33

CASE 10.-Male, aged 17. Frohlich’s syndrome(hypothyroidism) with diminished glucose tolerance(by courtesy of Dr. Leonard Abrahamson) .... Exactly

normal

CASE 11.&mdash;Female, aged 50. Paralysis agitans withpronounced tremor. Patient very apprehensiveowing to psychical disturbance...... +30

Second test with patient calm........ +11CASE 12.-Female aged 19. Intellectually deficient;dry scaly skin, hair of head has been falling out;partially deaf; some pigmentation of skin offorearms. Question of hypothyroidism in diagnosisdisproved by test .......... +13

’ (a) It is not intended to convey the impression that the effectof iodine, in benefiting cases of Graves’s disease, is permanent.(b) Tests given in order during the ten months of observation.

REFERENCES.1. Lusk, G. : The Science of Nutrition, Philadelphia, 1917.2. Benedict, F. G. : Jour. Amer. Med. Assoc., 1921, lxxvli., 247.3. Kendall, E. C.: Ibid., 1915, lxiv. 2042 ; Jour. Biol. Chem.,

1919, xxxix., 125.4. Plummer, H. S. : Jour. Amer. Med. Assoc., 1921, lxxvii., 243.5. Boothby, W. M. : Ibid., 1921, lxxvii., 252.6. Du Bois, E. F.: Ibid., 1921, lxxvii., 352.7. Kendall, E. C.: Jour. Biol. Chem., 1919, xxxix., 125.8. Kendall, E. C., and Osterberg, A. E.: Ibid., 1914, x]., 265.9. McCann, W. S.: Calorimetry in Medicine, Baltimore, 1924.

10. Benedict, F. G. : Amer. Jour. Physiol., 1909, xxiv., 345 ;Boston Med. and Surg. Jour., 1918, clxxviii., 667; 1920,clxxxii., 243 ; 1920, clxxxiii., 449.

11. Carpenter, T. M., Hendry, M. F., and Emmes, L. E.: BostonMed. and Surg. Jour., 1919, clxxxi., 285, 334, 368.

12. Roth, P.: Ibid., 1922, clxxxvi., 457.13. Roth, P.: Ibid., 1922, clxxxvi., 491.

(References continued at foot of opposite page.)

225

(Continued from previous page.)14. Rubner: Zeitschr. f. Biol., 1883, xix., 549.15. Du Bois and Du Bois : Arch. Int. Med., 1915, xv., 868 ;

1916, xvii., 863.16. Benedict., F. G.: Jour. Biol. Chem., 1915, xx., 263.17. Harris, J. A., and Benedict, F. G. : Carnegie Inst. Wash.,

1919, Pub. No. 279 ; Jour. Biol. Chem., 1921, xlvi., 257.18. Dreyer, G. : THE LANCET, 1920, ii., 289.19. Benedict, F. G., and Talbot, F. B. : Carnegie Inst., Wash.,

1921, Pub. No. 302; Talbot, F. B. : Amer. Jour. Dis.Child., 1921, xxi., 519.

20. Benedict, F. G., and Hendry, M. F.: Boston Med. andSurg. Jour., 1921, clxxxiv., 217 et seq.

21. Boothby, W. M., and Sandiford, I. : Jour. Biol. Chem.,1922, liv., 767.

22. Roth, P. : Bull. Battle Creek Sanatorium and HospitalClinic, January, 1923.

23. Du Bois, E. F.: Basal Metabolism in Health and Disease,Philadelphia, 1924.

24. Boothby, W. M., and Sandiford, I. : Jour. Biol. Chem., 1922,liv., 783.

25. Kessel, L., et alia: Jour. Amer. Med. Assoc., 1922, lxxix.,1213; Arch. Int. Med., 1923, xxxi., 433 ; Amer. Jour.Med. Sc., 1923, clxv., 387, 513.

26. Means, J. H., and Burgess, H. W.: Arch. Int. Med., 1922,xxx., 507.

Bootbby, W. M., and Sandiford, I.: Laboratory Manual ofthe Technique of Basal Metabolic Rate Determination,London, 1920.

PARA-SMALLPOX 1

(SYNONYMS ALASTRIM, AMAAS), AN ACUTE SPECIFIC

INFECTIOUS DISEASE DISTINCT FROM SMALL-POX.

BY R. P. GARROW, M.D.ABERD., D.P.H.,MEDICAL OFFICER OF HEALTH, CHESTERFIELD.

IT is a matter of common knowledge that therehas prevailed during the last few years in certaindistricts in England, chiefly in the Midlands andnorth, a disease notifiable as

"

small-pox." Thisdisease presents clinical and epidemiological featureswhich distinguish it from virulent small-pox as

commonly observed in England in recent times and Ias described in standard English text-books of’medicine and in Ricketts and Byles’ classical mono-graph the " Diagnosis of Small-pox."The features which distinguish the prevailing

disease from classical small-pox are so numerous, sostriking, and so constant, and their practical signi-ficance to physician, epidemiologist, public healthadministrator, and public is so important that inthe following clinical description I have adopted2 " para-smallpox " as its name in order to facilitatecomparison and contrast between it and the graverdisease small-pox.The disease is, in all probability (?), the same as

that known in South Africa as " amaas " (the Kaffirword for sour milk), and in South America as " alas-trim " (from the Portuguese alaster, meaning " tostrew over "), but inasmuch as these foreign nameshave no obvious meaning in English, I prefer " para-smallpox "-a name which at once conveys themeaning " a disease closely allied to small-pox."The coining of a new name is not intended to suggestthe discovery of a new disease, but merely to indi-cate its recognition as a definite clinical entity-anacute specific infectious disease separate and distinctfrom small-pox-a disease, moreover, which is fixedin type and does not tend to assume virulence andacquire the death-dealing and disfiguring properties ofsmall-pox.

Personal Experience.The clinical description of para-smallpox which

follows and its contrast with small-pox are basedentirely on personal observation of 500 cases occurringin the borough of Chesterfield between October, 1923,and July, 1924, before and during their isolation atSpital and Morton small-pox hospitals. The datawere all collected by myself from these patients andtheir relatives. Any personal error involved there-fore is mine, and not that of the ambulance nurse or

1A paper read to the Fever Hospital Group of the Society ofMedical Officers of Health, London, Nov. 28th, 1924.

2 See Brit. Med. Jour., May 13th, 1922.

sanitary inspector or other person concerned withthe outbreak. Thanks to the kindness of colleaguesin Derbyshire and elsewhere, I had opportunities forstudying para-smallpox for two and a half yearsprevious to its appearance in the borough of Chester-field. For example, I am indebted to Dr. HerbertPeck, medical officer of health, Chesterfield ruraldistrict, for the opportunity of observing cases fromNorth-East Derbyshire. I have also visited Ilkeston,Long Eaton, Doncaster, Gloucester, Middlesbrough,and other towns where the same or a similar milddisease has prevailed, and I am grateful to medicalofficers of health and medical superintendents ofsmall-pox hospitals in these towns for permission tosee their patients.My experience of classical small-pox is confined to

cases seen in the East during the war, but owing tothe kindness of Dr. A. F. Cameron, medical superin-tendent, small-pox hospital, Dartford, I was enabledto refresh my memory of that loathsome diseaseby a visit in 1922 to the patients from the Poplarepidemic.

Brief Clinical Description.For brevity and, so far as it goes, accuracy, I

cannot better the description of his disease givenby a patient in three words : " pimples followinginfluenza." In these words he brought out the threemost remarkable clinical features of the disease-first, the primary toxaemia which was almostuniversally regarded by both patient and doctor asan ordinary attack of influenza ; secondly, the focallesion, which, smaller and more superficial in theskin than the eruption of small-pox, is accuratelydescribed as " pimples " ; thirdly, the word " follow-ing " signifies one of the most striking features of thedisease-namely, the fact that frequently the eruptionappears after-it may be several days after-thepatient hascompletely recovered from the initialillness.

Analysis of Clinical Signs and Symptoms of Para-smallpox with Special Reference to Comparison

and Contrast with those of Small-por.1. Onset.&mdash;The onset of an average case of para-

smallpox is gradual, with headache, dizziness, achesand pains in body and limbs, and weakness of legs.These are the commonest symptoms complained of.In addition, there may be shivering, nausea, vomiting,abdominal pain, backache, and sore-throat. No case inthis series gave the classical onset of small-pox withrigor, vomiting, lumbo-sacral pain, and rapid prostra-tion. Although not prostrated, the para-smallpoxpatient usually lies down to recover from what hecalls influenza. His temperature in this stage is 100&deg; &deg;

to 103&deg; F., and subsides by rapid lysis. The recoveryfrom this initial illness is rapid and complete, and inthe average case the patient feels perfectly well forthe remainder of his attack, including the stage oferuption and convalescence. The influenzal illnessleaves behind no feelings of physical weakness or

mental depression such as frequently follow ordinaryinfluenzal attacks.

2. The Pa2zse -W’hereas in small-pox the eruptionappears fairly constantly in the middle of the primarytoxaemia&mdash;i.e., about the third or fourth day of the

TABLE I.&mdash;Showing the Duration of the Prodromal Illness.

illness-in para-smallpox its appearance is frequentlydelayed till the patient has completely recovered,and in about one-third of the cases an interval ofone to four days of complete intermission of allsymptoms occurs between illness and rash. In this

E 2