Por el camino de la síntesis | Fundación Dr. Antoni Esteve

(1)

Nov. %, 194.] A1NTITYPHOID INOCULATION STAT[STLCS. r *.

¹²⁴³

absence ofanyoedemawheretheglandswerehealthy, and of anydefinitenoticeable oedema in the mucousmembrane (of polypuscases)taken from regions where no glandswere present; (2) the appearance of abruptoedemaassociated with a patch ofglands in a state of cystic degeneration. This was noticedinalargenumber of instances, of whichFig. 6 is an illustration of one example. In the portionsof thesection contiguoustothepartshown, theglandswereactive,and the tissues superficial tothemwerenot oedematous. There can be seen the abruptinterpositionofalayerofglands,inastate of cystic degeneration, drawn like a broadboundaryacross the section. The tissues superficial tothis layer of glands wereoedematous ; but there were noevidences ofgradually increasing inflammatory change or of the gradual develop- mentof oedema.

It ispossible that thepeculiarandspecialmethod in which thebloodissuppliedtothe glandsin the turbinal regions- combinedwith the predisposition to oedemainduced by the histological peculiarities of the middle turbinal regions- mayhelp toexplain whyoedema onlyoccursin certain cases ofinfiammatorydisease.

Ztickerkandl's account2of thearrangement ofblood vessels inthe turbinal regions is,brieflyandasit appears to concern the present subject, as follows: The arterial supply of the mucousmembraneramifies in three networks. One network supplies the periosteal layer,a second is distributed to the glands,and a third to the superficial epithelial layer. The glands,which aresurroundedbyaspecialcapsule,areclosely enveloped by their network of capillaries. Around the excretory ducts there is a tube-shaped network which, as Zuckerkandlbelieves,helps to keeptheductclosedwhen the gland is not activelysecreting. When themucous gland and the duct (which always participates)undergo cystic dilata- tion, pressure is exerted on the rdseau of vessels which encircles the gland, and on the tubular network which is around the duct. The writer believes that this "unequal pressure"on thecapillaries may besufficient to cause oedema Inthe particular areasand tissues inwhichthe phenomenon isnoted. The suggestion,however, is at present purely con-

jectural.

THE INFLUENCE OF STRUCTURAL PECULIARITIES OF THE

"POLYPuS REGiONS."

The structuralpeculiarities in the polypus regions, which have been referred to, appeartobe necessary auxiliary factors -othercauses,forexample,inflammation andgland degeneration,intervening-for the occurrence of polapns at certain ages negativelyforits usual absence at certain otherages, and,lastly,forits occurrence, inthespecial districtsinquestion, when a specific irritant, such as pus from an accessory sinus, i8 present. Moreover, even assumingthat degeneration andcysticdilatation of themucousglandscanbeshewn to determine the initial stages of polypus formation, they (glandular changes) cannot apparently have these effects unless thesubepithelialtissuesaresufficientlythin andloose.

Thus,in some instances of

polypus

themucousglands were degenerated,inplaces,throughoutthe nose, although polypi andoedemawereonlyseenin'themiddle meatal and a part of themiddle turbinalregions. Also inaninstance of chronie atrophic rhinitis there were a few groups of degenerated mucous glandsin theregionof themiddleturbinal,without anyevident oedemaintheatrophiedandfibroussubepithelial tissues.

PROVIsIONXL CONCLUSIONS.

Thefollowing provisionalconclusions are brought forward for discussion and-further

investigation:

I. Mucouspolypiof thenose, inthe

majority

of instances, are probably consequent upon, and

certainly

coincident with,inflammation of the mucous membrane of the nasal cavity.

2. Theprimarymechanical process isalocalized oedema of the inflamedmucousmembrane, which

oedema,

onaccount of certainstructuralpeculiarities of the

lining

membrane,does not, in thegreatmajorityof cases, develop in anyintranasal areabutthatofaportion of the middle turbinal and of the middle meatal regions. Analogous structural peculiarities arepresentinthe mucous membrane ofsomeof the accessory Sinnse8.

3. Thedeterminingcauseoftheoccurrence of the oedema, intheregionsspecified,isthe

degeneration

andcystic dilata- tionofthemucous

glands.

4. Theparticular ehapewhich

polypi usually

assume, their number,

probably

the appearance, in some

instances,

of recurrence,and other

special peculiarities

of these

growths,

aredue to the oedematous mucous membrane being thrown into folds, and to the normal folds becoming oedematous.

Certain of thefolds

quickly

increase in sizeby the absorption of serous fluid and favoured by gravity, and finally present the appearanceof ordinary mucous polypi.

5. The "polypoid" outgrowths, which take origin on the interior turbinal, and more rarely on the septum, generally differ markedly in microscopic structure from mucous polypi, and although they claim a common inflammatory origin, these conditions are distinct, principally on account of the dissimilar structure of the nasal regions from which they respectively take origin(Zuckerkandl2).

The writer is at present arranging to conduct some experiments, with the view of producing mucous polypi artificially inanimalson the basis of the causativeinfluenceofglandular changes.

Inconnexionwith this paper, the writer is greatlyindebted formuch kind andvaluableassistanceto ProfessorSymington, of Belfast, to Dr. Milligan, Professor Del6pine, and Dr.

Knowles Renshaw, of Manchester, to Dr. W. Glegg. of Birmingham, and, lastly, to Dr. Reginald Nichol, of Man- chester, who has shown much

accuraey

andskill in connexion with theillustrations.

NOTEANDREFERENCES.

1Heyman, Handbuch derLaripigologie tndRhinologie. Band iii,Heft ii, Wien, T900.I 2Zukerkandl, Anaunnie des FPsseNasales. Trad. sur la 2e ddition allemande par Lichtwiiz et Garnault, Pnris, £895. 3 The wr ter has not touchect, in the presentpaper, on the subject of the influenceofbonedisease in theproductionof nasal polypi, because his observations,especiallyofearly cases, haveled him to believe that there is sufficient evidence of the process occurriDg as a primary mucous membrane condition. 4 Grunwald, Diseases of the Mouth, Pharynx, and Nose,secondedition, trans. by Newcomb, Philadelphia and London, 1903.

REPORT ON CERTAIN ENTERIC

FEVER

INOCULATION STATISTICS.

PROVIDED BYLIEUTENANT-COLONEL R. J. S. SIMPSON,C.M.G., R.A.M.C.

By KASRL PEARSON, F.R.S.,

Professor of AppliedMathematics,University College, London.

THIEstatistics in questionwereoftwo classes: (A)Incidence (B) Mortality Statistics. Under each of these headings the databelonged to two groups: (i) Indianexperience; (ii) South African War experience. These two experiences were of a somewhat different character. That for Indiaeovered apparently the European army, of whatever branch and wherever distributed; that for South Africa was given partly by locality, partly by column, and partly by special hospital.

Thus the Indian and South African experiencesseem hardly comparable. Many of the groups in the South African experiencearefar too small to allow of anydefinite opinion being formed atall,having regardtothe size of theprobable errorinvolved. Accordingly, it was needful to group them intolarger series. Even thus the material appears to be so heterogeneous, and the results so irregular, that it must be doubtiul how much weight istobeattributed to the different results.

Thefollowing groups were made on the basis ofLieutenant- Colonel Simpson's table (see Appendix A).

A. Incidence.

South Africa:

I. HospitalStaffs. SeeAppendix B, Table(X).

If. Garrison of Ladysmith. SeeAppendix B, Table(2).

III. Methuen'sColumn. SeeAppendixB, Table(3).

IV.Group of three special Regiments: 7th Hussars, C.I.V.'s, and 5thBattalion Manchesters. SeeAppendixB,Table(4).

India:

V.sArmy in India. Here I have takenonly the data for years 0oo0 and 190I,asIamtoldthat the statistics for I899 are notfully comparablewiththoseforthe two later years. SeeAppendix B,Table(s).

B. Mortality.

South Africa:

I. Hospital Staffs. SeeAppendix B, Table(6).

II. GarrisonofLadysmith.* SeeAppendix B, Table(7).

III. Special Regiments. SeeAppendixB, Table(8).

IV. Group of specialHospitals, South Africa. SeeAppendix B, Table(9).

V.Variousmilitary Hospitals. SeeAppendix B,Table(lo).

India:

VI. ArmyinIndia,z9oo.-. SeeAppendi B,Table(I).

*Nomortality experiencewasgiven in the caseofMethuen's column.

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---

After some

consideration,

^it seemed best to reduce the above data

by measuring (i)

the association of inoculation andescape;

(2)the

association ofinoculation and recovery

by

aid of thecoefficientof correlation'extractedfrom the four- fold tables

given

in

Appendix B, by

the method treated in

ame-moir

published

in the

Philosophical Transactiow,

vol.

I95, A,

pp. I to47, igoo. The chiefreason for

using

this method

isthat it enablesus at once to compare the enteric fever inoculationreturns with the results for vaccination and antitoxin tr-atment in thecaseof

diphtheria,

whichhave

already

been

dealt

with inthismanner.

Fi)r

sxample, taking

the relation between deaths and

recoveries,

and presence andabsence of vaccination scar in casesof

small-pox,

wehave:2

Correlation.

Metropolitan Asylums Board Returns,

Epidemic1893 ... ... ... o.59s ± 0027

Epidenicisfor£ixtowns ... ... o.6s6 ±ooog

Sheffield,I887-8 ... ... ... 0.7t9±0.012 HomertonandFixlham,

I873-85

^... 0.576 ±ooog Loudon: Epidemic19o0 ... ... 0.578±0.031 Glasgow: EpidemicigooI ... ... 0.629 ±0.030 We may

safely

say that the

protective

characterofvaccina- tion as

against mortality

after incurring

small-pox

is very

substantial,

^and

numerically

^itis

represented by

thevalueo.

6,

which is

fairly closely

the actual result for the variuus

epidemics

^which haveat

present

been dealt with.

The correlationbetween recovery and theadministrationof antiti-xinin

laryngeal

casesof

diphtheria

is0.47,andbetween need for

tracheotomy

andthe administration of antitoxin is

o.24.3

We may therefore state that when the

correlation

is as

high

aso.6itisadmitted that inoculationorvaccination is a

dibtintct advantage; that,

even when it is 0.24 to

o047,

it has been

universally adopted,

as in the case of the antitoxic serum treatmentof

diphtheria, by

the medical profession.

If, therefore,

with enteric inoculation we

End

values as

high

as

o.5,

we may rest satisfied with its very considerable effectiveness; if between

0.2 and

0.5,

^its

justification

stands on the same statistical

looting

ad the antitoxin treatment of

diphtheria; but,

if we find the value below 0.2, or even 0.3, we

ought

tobe rather doubtful of its

efficiency.4

Before

working

out the data the

impression

formed on my mindwas that ifthe correlations turned out to be

fairly

constant and greater than

0.4,

^we

might

consider the casefor inoculation

against

enteric

proven;

if

irregular

and less than 0.2, unproven- that

is,

it must be of very small value,

possibly

more than balanced

by

concomitant ills;

while,

if

lying

between 0.2 and

04,

further cautious

investigation by experimental

inoeulation seemed desirable.

The

following

table

gives

the results of

calculating

the

correlation

coefficients of thetablesin

Appendix

B:

INOCULATION AGAINSTENT9RIc FEvBR:

CorrelationbetweenImmunityandInoctuation.

I. HospitalStaffs... ... ... + 0.373 ±

0.0s2

II. LadysmithGarrison ... .. + 0-445 ± 0.017 III. Methuen'sColumn ... ... + o.xgi ± oo26 I,V.SingleRegiments ... .. + 0.021 ± 0.053

V.ArmyinIndia ... ... ... + O.I00 ± 0.013 Meanvalue ... ... ... + 0.226

CorrelationbetweenifortalityandInoculation.

VI. HospitalStaffs... ...

0...

+ 0.128

VII. LadysmithGarrison ^... ... - oozo ±

os081

VIII. SiDgle Regiments ... ... + 0.300 ± 0.09t IX Special Hospitals ^... .. + o.9 ± 0 022

x.Variousmilitary

Hospitals

... + 0.194 ± 0.022 XI.ArmyinIndia... ...^... + 0.248 ± 0.050

Meanvalue ... ... ... + 0193

If we

except

^{IV and}

VII,

the values of the correlations

areat least twice

(in

theverysparsedataof

VI)

and

generally foul, five,

or more times their

probable

errors.

From

this standpoint we

might say

that

they

areall

significant,

butwe areatonce stiuckwith the extreme

irregularity

and the low-

nessof the

values

reached.

They

are

absolutely incomparable

withthe

fairly steady

and

large.values

ofthe vaccination cor-

relationsobtained for

different epidemics

and towns. The effectofentericinoculationis

evidently largely influenced

by

diffprence

of environmentoroftreatment.

Considering

the correlation between

immunity

inoculation, theorder of

decreasing intensity

is:

LadysmithGarrison.

HospitalStaffs.

Methuen's Column.

ArmyinIndia.

SingleRegiments.

Indeed, while

the correlation is

Sensibly

zeroin the latter case, it is

actually negative

for the

C.I.V.'s.

Now,

the one

thing

that appears in broad outlines to corres ond withthe above

arrangement

is the extent to which theenvironmentwas

changeable

in the

gronps

referredtow The

single regiments

were very

rapidly changiig

their environment-the a.

[.V.'s, perhaps,

^more than

auiy

other

group-the Ladysmith

garrison

least,

and

Methuen's

column

moremobilethan the

Ladysmith garrison,

but far less than the

single regiments.

I am unaware how far the inoculated

portions

of the Indian armywere

seeing

actual serviceof any kind

during

the yearsi9oo to I9o0.

But,

so far as these statisticscan

guide

usat

all, they

wouldseemto

suggest

that, inoculation

provided

more'

immunity

under constant than

changing

environment. It is difficult to

explain

thisonthe basis o1 any real

theory

of inoculation." Itwould be easier to account forit if the

apparent

correlation between inoculation and

immunity

arosefromthemore cautious andcareful

men

volunteering

forinoculation. It is far moreeasyto be cautious under a constant environment than wheni the environment is

nightly changing.

The order of intensities is not

inconsistf

ntwithaspuriouscorrelation between

immunity

and

inoeulation arising

from a real correlation between

immunity

andcution.

Putting

on one

side, however,

the

mysterious

^difference

betweentheo 445of

Ladysmith

andthe

practically

zeroresult for the

single regim. nts,

and assuming that the average correlationisreal and 0.23

about,

wemaydoubt whether this is

sufficiently large

to

justify

thetreatment

being adopted

as

routine. I thinkwemay

safely

say that the o.i of theIndian army is not. Of

course,

if the

Ladysmith garrison result

could be

practically

reached for all

units,

whatever their

environment,

it would be worth

doing,

almostaseffectiveas

the

diphtheria

antitoxin

treatment, although

still farbelow vaccination

efficiency.

But can anydifferentiation be dis-

covered, except

the

stationary

nature of the

troops

between thetrestmentandenvironmentat

Ladysmith

and those, say, of theC.I.V.'s P The matter is at least worth

inquiring into.

If we turn from

immunity

to

mortality

^{we see}

tkiat

the results are even less conclusive. The order of

increasing intensity

isnow:

LadysmtthGarrison.

SpecialHospitals.

Military Hospitals.

ArmyinIndia.

Single Regiments.

HospitalStaffs.

The last itemisofsmall

value,

asthe

mortality experience

was very small.

Generally

this order is thesame as that of

decreasing immunity,

or,

roughly,

^the environment which

causesinoculationto

give

the

greatest immunity

also causes, when

immunity

has broken

down,

inoculation to have

relatively greater mortality.

In

fact,

the inoculated in

Ladysmith,

once

they

had the

disease,

^were more

likely

to die than the

non-inoculated.6

Again,

if any stresscouldbe laidonthe

result,

^{it is}

most mysterious

that an inoculated man, if he

caught enteric,

profited less by his inoculation in

Ladysmith

than if he had been with oneof the

single

mobile

regime

nts; while he would be much less

likely, relatively

^to ^the

non-inoculated,

tocatch it in

Ladysmith

than inamobile group.

NEED FOR FURTHER

INVESTIGATION.

To sum up, iWseems

that,

while most of the

correlations

both for

immunity

and

recovery

are distinctly

sensible1 having regard

to

their probable

errors,

yet they

are so

irregular

that little reliance can be

placed

upon them as

repr-senting

any definite uniform effect.

They certainly

appeartofallintothat range of

intensity

which would

justify suspension

ofthe

operation

as a routine method. But the fact that the

correlation,

while

sensible-and,

in the (ate of the

Ladysmith garrison, moderately

substantial-is

tubject

toremarkable

variations,

seems to

urgently suggest

theneed forfurther

investigation.

This

might

takeatwo-foldform:

i. An

inquiry

^asto what

happened

at

Ladysmith.

Did the

serum ortheino(ulation

differ

inany way from thatusualin India or that administered to the

C.I.V.'s.

On the

whole,

were the inoculated and uninoculated at

Ladysmith

in

different units, and,

if so,wasthe exposure to

ribk

thesame

inbothcases?

2 An

experimental inquiry.

If further

experimental

inoculations were

made,

^{which seem} fairly

justified by

the

Lad}

^{smith if}^not

by

theother

returns,

the

greatest

care

ought

tobe takento

get homogeneous material,

that

is,

^menoflike

TM mb. 'I

1244 oft="Zfoaux"i ANTITYPHOID INOCULATION

STATISTICS. [Nov.

^{5, t904}

(3)

Nov.

5,

'904.1

ANTITYPHIOID

INOCULATION STATISTICS.

I awanoz^TM ^Iz24loww 1 4 caution,, subjected to thesame environment. Assumingthat

theinoculation is not more thana temporary inconvenience, it would seemtobepossible to call for volunteers, but while keeping a register of all men who volunteered, only to inocu- lateeverysecond volunteer. Inthis way any spuriouseffect really resulting from a correlation between immunity and cautionwould begotridof.

But admitting that such an experiment mightconclusively answerwhetherthere is a correlation between immunityand inoeulation, and, further,thatinquirymightsuggestameans of thrusting up the general mean result nearer theLadysmith figure,itseems to me thatthepresentstatisticsshowthat with the existing serum orthe method of administration it is ex-

tremely

unlikely that the effect of entericinoculation will be as good as the antitoxin diphtheria treatment and will certainly fall far shortLof the mortality7 resultin thecaseof vaecination.

If it were notpresumptionfor mewithnospecial

knowledge

whatever on the subject to give an opinion, I ahould say that the data indicate that a more effective serum or effective method of administration must be found before inoculation ought to become a routine practice in the army. The statistics suggest the possibility of the dis- covery of a more perfect process, rather than indicate that. the existing method, even if it be shown to give a slight correlation between immunity and inoculation, is really worth continuing as a universal rule of thebervice.

Hence such an experiment as thatindicatedabove shouldbe madein the first place with a view to ascertaining whether any inoculation is likely to prove

useftul.

If it showed a definite correlation in homogeneous material of only 0.2or 0.3, 1 think theright conclusiontodrawwould be notthatit wasdesirable to inoculate thewbolearmy, butthatimprove- mpntof

the

serumandmethodof dosing, withaviewto afar highercorrelation. shouldbeattempted. Inotherwords, the

"expe-riment"

might demonstrate that this

first

step to a reasonably effective preventive treatment was not a false

one. APPENDIX A.

INOCULATION.

Inoculated. Non-Inocu- _____- ___ ____lated.

Group. _.

d a0 Q

Staff PortlandHospital^... ^... . 8 7 - 13 3 x

I Y Deelfort... ... ... ... 59 4 - 25 4 -

I. Y. Pa.(1) ... ... ... ... 12 2 - 38 3 -

I Y.Pa.(2) ... ... ... ... 20 I - 34 4 -

9 No 8GeneralHospital ^... ^.. 2 5 - IO 44 8

.0, No.9 ,, ft ... ...87.2I I 47 13 2

,, 2nd Be.RedCross ... ... 70 I 12 4 I

297 32 2 279 75 -12

Garrison,Ladysmith ... ... 1,705 35 8 10,529 1,489 329 Methuen's Column^... ^... ^... ... 2,535 26 7 ro,g8x 257 ?

4,240 6i 21,510 1,746

sth

BattalionManchesters 200 3 - 547 23 7

C.l.Vs... ... ... ... ... 700 6o 9 494 39 11

7thHlussars ^... ... 307 9 - 244 20 3

1,207 72 9 1,285 82 21

India, I899 ... ... 4,502 44 9 25,851 657 T46 ,, 9eo ... ... ... ... ...05,999 5- 8 54,554 731 224

to 1901 ... ... ... 4,883 32 3 55955 744 199 15,384 128 20 136,360 2,T32 5(9

TintovvnHospital^...^..^. ^- ³⁰ 2 - 265 5

No. 7 GeneralHospital ... ... - 137 3 - 1,017

55

Im.Yeo.Hospital... ... .. _ 47 4 - 301 26

No. g GeueralHospital ... ... - 387 32 - 586 64

Ir.lshHospital ...... . - 80 5 - 592 74

No.6General Hospital . .. o 5 - 477 58

Noxit ,9.. . - 32 6 - 194 22

PortlandFloe i.a.. 54 4 - 178 25

Stat,ion. HospStal,Harrismith. .. - 63 I8 - 947 135

Scot.Nat.itdCross ... - 5 1 - 70 10

No. 5statIon.Hospital ... - 24 2 - 53 8

No 2GeneralHospital ^... ... - 28 3 - 202 31 Orange hiverHospi ... ... - 27 I - 109 22 - 1,174 86 -

4,99'

538 VariousMilitaryHospitals - 764 63 - 3374 5O

APPENDIX B.

A.-INCIDENCE EXPERIENCE.

Inoculated. Non-inoculated. Totals.

I.HospitalStaffs inSouth Africa.

Escaped ... ... 265 204 A69

Cases ... 32 75 1 IC7

Toals ... 297 279

j

576

2. GarrisonofLadysmith inSouthAfrica.

Escaped ^... . .. |

I,670

9,040

10.710

Casescae... I 35 1,489 1__524 _

Toals ... 1,705 10,529 12,234

3.Ifethuen'sColumn in SouthAfrica.

Escaped 2,509 10,724 1I3,233

CaSpes ... ... 26 257 283

Totals ... ...I 2,535 10,981 13,5I6

4.SingleRegimentsinSouthAfrica.

Escaped ..,19135 1,203 2,338

Cases ^... 72 82 154

Totals . . ,207 1,285 2,492

5. ArmyinIndia.

Escaped 10,798 IM9,034 1I19,832

Cases .84 1,475

'.559

Totals ... ... I0,882 110,509 121,391

B.-MORTALITY EXPERIENCE.

6.HospitalStaffsinSDuthAfrica.

Recovered... 3° 30 63 93

Died . ... ... 2 12 14

Totals . ... 32 751' I07

7.GarrisonofLadysmith.

Recovered... 27 | I,I6o | 1,187

Died . ... 8 329

-_337

Totals. I 35 1,489 1,524

8. SpecialRegimentsin SouthAfrica.

Recovered ... 63 6i I 124

Died 9. ... . 21 30

Totals. 72 82 1'54

9. SpecialHospitalsinSouthAfrica.

Recoveredo... | ,88 4,453 5.541

Died 86 538 624

Totals ... ... ,174 49991 6,65

Io. VariousMilitaryHospitalsofSouthAfrica.

Recovered... 701 2,864 3,565

Died ...63 1 510 573

Totals ... .I 764 3.374 4,138

iI.ArmnyinIndia, 1900-1.

Recovered... 73 1,052 1,1252

Died ^.. ^... ... II ! 423 434

Totals ... ... 84 | 1,475 19559

NOTESANDREFERENCES.

Those who havenot hadoccasiontostudytheTheoryof Correlation mayposqiblyfird some difficultyinattaching adefinite

meaning

^tothe

expression

"coefficientof

correlation,"

usually denotedbytheletter

r."

"

Without

goiug Into

thetheoryof the subject, I offer afewexpl4natory remarkswhih mayto some extentclearup

t,he

difficulty. When two characters have no correlation at all thenr=o;when

t,hey

are com-

pletelycorrelated,orwhen theideaofcorrelationpassesoverititothatof causeand

effect,

^r⁼r. The extremelimits betweenno relationshipand cause aldeffectbeingoandi,rmaytake any valuebetween thelimtts,

the valuedependingontheintensityof therelationshipbetweenthetwo

eharacters. We maycalculaterforapairof charactersinonecia-s-for example.forrightandleft femur inman. orfor two classes

with

respect

toaselected character-forexample,forEnglishmiddle-class fat-hers and sonswith

respect

to stature. Manysuch calculati-ns ha,ve been mate, and fromthemassofresultsalready obtainedIselectthefollowing:

Highcorrelation Rightand left femur inman ... ... ... r=o96

0.75to1. Statureandfemur inman ... ... ... ...

0r

⁼ 80

Cosidemble {Weightandleogthof new-born infants ... r=o63

correlutaon Headbreadlhandfacebreadth in criminals... r=o.62 correlation ~ Vaccinationand recovery incasesofsmall-pox r=o6o 0.50 to0.75. Englishfathersandsons(stature) ... r=0.51

Moderate Englishfathersanddaughters (eyecolour) v=

0o44

correlation Lowbarometer(Norway)andhighbarometer

025to0.50. (Lisbon)... ... ... ... .. ... =0.30 Low correlation Strengthof pull and statureinwomen... ... r=0.22

0to02S.

Size

^offamily for mother and daughter (in 0100.25. man) ... ... ... ... ... ... ... r=

O.II

2Macdonell,

Biometrika,

vol. i, p.

375.

et seq., and vol.ii,etseq. ³

Pearson,

Phil. Trans..vol.cxcv,A. p.45. 4Writingin igooof the

diphthei

isanti- toxinstatistics,Isaid: Thecorrelatinn " betweenadministrationofanti- txinand recoveryin

laryrgeal

casesissubstantial. Butthe

relalionshiD

isbynomeanssogreatasinthecaseofvaccination,and ifitsmagnitude

justifies

theuseofantitoxin,evenwhenbalancedagainstotherilswhich mayfollowinitstrain,Itdoes not

justify

thesweeping statemenlaofits effectiveness,which I have heard made bymedical friends It seems, until widerstatisticsare forthcoming, acase forcautiouslyfeelingthe

I 2

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1246

M2DTO

Jl MEMORANDA. [Nov. 5, 1904 way forward rather than for hasty generalizations." Unfortunately

further statistics of the proper kind are not forthcoming. owing to the nearly uDiversal adoption of the treatmeit in severe cases.

5Supposing,of course, the avenue to the disease is always the same. If inoculation closedone avenue but not another to the disesse-say effect of contact with enteric patients, but not of contaminated water- itis clearthat constant and changing environment mightmodify the relative prevalence of the twopossibilities. 6Wemust bear in mind the possibility of inoculation produciDg a weakeniDg of the constitution, and thatthisismoreeffective when the soldier is stationary than when he is onthe move. 7Strangely enough, we haveDoreliahle statisticsonthe immuoity correlation invaccination, as the number of unvaccinated who do not catch small-pox appears quite unknown.

MEMORANDAI

MEDICAL, SURGICAL, OBSTETRICAL, THERA-

PEUTICAL, PATHOLOGICAL, Ekc.

APR&CTICAL SUGGESTION FOR THE PREVENTION OF ANKYLOSTOYIIASIS.

OF the many troubles with which the planter -in tropical countries has tocontend, not the least is coolieanaemia, and the disabling form of pustular dermatitis variously called coolieitch, grounditch, etc.

The dependence of coolie anaemia onankylostoma infection has long been recognized, and the probability that the form ofdermatitiscalled coolie itch isproducedbythepenetration of the skin of the feet andlegs bytheembryosofankylostoma contained incontaminated soil is now, from theobservations and experiments of Looss andBentley,practically acertainty.

We arethereforeina positiontoindicatewithprecision the direction ofprophylacticmeasures againstbothphases of this infection. Unfortunately, although it is easy enough to indicate measures which tbeoreticallywould be efficient. to getthem appliedis a verydifferentmatter. Atthesuggestion ofBentley,

boots

andbathsof carboliclotion have been

tried,

but so far apparently without striking results, in great measure in consequence of the want of co-operation on the part of the coolies.

Some time ago, in the course ofaconversation withaWest Indian sugar planter, I learned of a method which in his hands had proved

efficient;

it appears to me to meet the circumstances, and deserves, I

think,

publicity and further trial. Thisgentleman, in ignoranceof Looss'sand Bentley's observations, had concluded that coolie itch was contracted from contact with faecally-fouled soil, and that somehow it ledup to coolie anaemia-tbat is, ankylostomaanaemia; he reasoned that, could he prevent the injuriouseffects of the contaminatedsoil,he would notonly prevent coolieitch,but theconsequentanaemia. Knowingthe antisepticandadhesive properties of green Barbadoes tar (a mineral oil rich in paraffin,andcheap, costing3d. a gallon), he got his overseers toseethatthecoolies, before going out towork in the contaminated fields, dippedtheir feet and legs in a bucket of this tar, and thenwalkedacrossandthrough somefinesand;

inthis way an impervious sandal and stocking was donned everymorning. Inpracticeitproved efficient. My informant suggests that sawdust wouldprobablybe better than sand.

He told me he got the idea from a practice exiatingamong goosefarmers in certain parts of Germany, who, byfirstdip- pingthe feet of their geese in tar and then in fine sand, provided the birds withaplastic and protective sandal, thereby enabling them to be driven manymiles to market without injury.

London,W. PATRICK MANSON.

OPHTHALMIA

NEONATORUM: TREATMENT BY ARGYROL: RECOVERY.

ON

July

8th I wasaskedtoseeachild, i6

days

old, whichthe

mother,

aprimipara, informed me

had.

been

suffering

since birthwithadischarge fromits eyes. The

history

wasthat the

midwife,

during her attendance, toldthe motherthatit was acommonoccurrence for children to

get

sore

eyes

likeher infant, andthatthey would get all right.

Asthe condition began to grow much worse, causing both eyes to be

firmly

glued together,

With

a profuge

discharge

of a

whitish

nature, it was decided to seek medical

advice,

as herownremedies of boraciC lotionhad failed.

-Examination revealed great chemosis, and

difficulty

was encountered on

separatiDg

the

lids,

when a

yellowish-white, Purulent discharge

was observed, which increased on

deep pressure.

The child. did not appear to be in much pain.

The

right

eyeshowed

keratitis,

with two

ulcers

onthe cornea, the left showing one

ulcer.

Lotion of corrosive sublimate

(x in

5,ooo)

was ordered every half-hour or hour, also the following unguentum: X Hydr. ox. flav. gr. ss; coc.

hydroc. and atrop.sulph.a& gr. j; vasel.spt. 3

ij,

which was to be applied at night, both pupils being very much contracted.

Asthecondition did not improve much in thirty-six hours, Idecided to use argyrol20per cent.,which I prescribed twice

daily,

with careful directions as to its application and cleanliness, etc. After the second application, improvement' manifested itself, and became so marked after the fourth application that the chemosis practically disappeared, the discharge greatly diminishing and becoming less purulent.

The corrosive sublimate, lotion was increased in strength (i in 3,ooo) and used as before, and the

argyrol

was dis6on- tinued for twodays,as aslight trace of the chloride ofsilver began to form. The course after the sixth day -was most satisfactory, and at the end of the eighteenth day alldis- -charge had ceased and the eye-sappeared quite healthy, only aslight manifestationof an ulcer remaining in therighteye.

A history of gonorrhopa was elicited from the mother,-the wife of a

soldier,

whohadnotundergoneanytreatment. The easeisinteresting from thepointofviewthatconsideringthe durationof the affection and the greatchemosis,etc., such a speedy recovery should follow after the use of

argyrol.

The friends and parentsof the child often remarked that'the change was wonderful after the second application, as the child opened its,eyes and the discharge

considerably

lessened.

Argyrol did not cause the patient any pain and no ill effects were produced;, on the wholeIthinkitismuch pre- ferabletoeitherprotargolornitrate ofsilver.

T. GARNET S. LEARY,

M.B.Edin.,

M.R.C.P.E.

Castlederg, co.Tyrone.

EPITHELIOMA OF PENIS ASSOCIATED WITH LEUCOPLAKIA.

1SAWthe patient first in October, i9o3, when he came com- plaining of a warty growth of the penis, which he first noticed as asmall wart a fewdays before leaving Chili for this country, whichwas onAugust 24th. He alsocomplained of someitching in the part, which had been going on for ten orfifteenyears.

ThepatientleftEngland twenty years ago quite well. He went to India, and stayedthere fourteen and a halfyears, but came home for holidays two orthree times. He first noticedthe itchingwhilst in Ind-a, and for this he used to wash himself in warm water. When the itching firststarted hewentto adoctor, who told him the condition was natural and he must justwash himself with soap and water. The patientthinkstheitching wascaused by wearing theforeskin overtheglans inahotcountry,the urinebeingacidandcon- centrated. As aboy the patient couldnotbearhis

foreskin

back. The itchingusedtocomeand go.

The patient has only noticed theconditionofmarked white- nesssincecoming toEngland,but hashadaslight whiteness for fully ten years. This would come and go away again.

Keeping the foreskinback and washing it caused the white- nesstodisappear and theitchingaswell,buthewasnotable tokeeptheforeskinback because the head of the peniswould commenbe to swell, and on one occasion he hadtohave a doctor to bring it forward again with a handkerchief and vaeeline-andthis with much difficulty. Afterwards hewas afraidtodrawtheforeskinback for fear of thesameresult.

Oncominghomeonboard ship the patientsays the water washard,andtlhat;salt water andhardwater did notcurethe whitecondition, but made it worse. Vaseline would cure it.

Thewartbasbeen growing rapidly.

Pre8ent Condition.-Tbe patient is a gentleman, aged 53 years. Helooks the sort of man who has livedahardlife, much in the open air. He is a mining engineer, and has livedmany years in the tropics. Be is thick-setandobese-

the neck is short and thick; the chest is well-shaped

and

massive; the abdomen is well covered with fat and is protuberant; neither liver nor spleen can be feltthrough its wall. The second Eound at the aortic base isaccentuated, but thesoundsatthe apex,thoughclearand

distinct,

aredistant.

Thebreath sounds are accompanied by occasional rhonchi, and the urine contains some albumen but no sugar. The penis has the foreskin over the glans, and looks

natura)

enough, except that there is some slight swelling over the region of the corona. On the patient pulling the foreskin back from the glans a circumscribed warty growth appears on its inner or glandular

portlion,;

it is situatedonthatpart of theprepucewhich layincontactwith