Document MMg246NwdzNm58yXooN7JgpRa
WiMWWwwli it V "imiaii
350 6 February 1965
Tetralogy of Fallot--McMillan
d o t closure of th e defect wfll he difficult w ithout the use of g u d l^ a tr B ^ ^ ta B p e ta tin e ern^be lowered^ t o j chc^ootrect
In one case where the defect was dosed by direct suture, one suture to te o u t and so damaged the reptum th at a patch had to be overlaid to cover th e tear. U nfortunately, in suturing this patch into poshion tricuspid incompetence was produced. The developm ent o f heart-btock some IS hours later was attributed to gross rig h t ventricular dilatation causing tension on the
It u encouraging th at, contrary to expectation, n o t experienced w ith respiration in A c post-operative
tracheostomy waa not required. T he children were nursed fiac in an oxygen ten t fo r 48 hours and were then gradaa% weaned from i t
In two caret th e children w ere bottie-fed w ithout difficulty,
but in all cases great care is needed to l
'
biochemical cqmHbrhnn.
of the four patients who
anatom ical features in td a e t et, ( m l } tetralogy of '
led heart-block bad
the V .SJX Sayed the V.SX. in the
from th is
closure o r if < the V .S J5. ;
T he prophylactic hasertion of a enefote pacemaker electrode
fe now <^yf
th e
nf
block o f late onset.
O f the ftair cases w ith teart-h telb : the s reh n r responded
norm ally to artificia! pacem aking, w hile the other three,
although they responded norm ally a t firs t rapidly developed an
itsBt&noG
vi^ngr
frooi 1 3 to 12
volts over 12 to 24 hours. They tin s became com pletely
resistant to any stim uhttion, and death followed. N o satis-
jtt all fjwey pn ^ ^ ff
nf
{tiafurlwnpn
became m anifest soon after the onset o f the block and severe
cerebral damage was found a t necropsy.
i age. o f S yeare were < ...
tetralogy of FaBot, using earths- -
pulmonary by-pass and deep h y pothecate, T to e were.A m t
fatalities. T en were acyaaotic and well, t i d e one was still
cyanosed owing to reopening o f th e ventricular septal defect
but was greatly im proved. T here were no respinm xy o r
haemorrhagic complications.
... , *
We should lice to foaafc M r. H. M. Bndmore for his asiteence
at all these operations ; Dr. M. Yorston, who provided anaesthesia ;
.....................I of the W essR e*iiB who referred the patiem tt
tte Cardiac and Thoracic Unit
: which this work would not baje
t possible.
,
Drew, C l ,,
,
Mtkovty D. Q. <19591 I - - - . ,V i ..... , -- , S & , B e J K a t r i M & s ^ a < W 2). [M eet, t , 54.
Diffuse Mesothelioma o f the Pleura and Asbestos
P. C ELMES,* MJ>., M.X.C.P. ; W. T. E. McCAUGHEY.f MJJ. ; O . L . WADE,* M JJ., p jtcjp ..
B rit. m td .} ., 1065, t , 0 - 3
. D iffuse mesotheliom a of the pleura is an uncommon tum our w hich, after prolonged controversy , haa now become generally ` as an en tity (Cam pbell, 1950; Godwin 1957; 1958; W agner, M unday, and H arington, 1962). s recently been accum ulating th at inhalation of asbestos m ay be an im portant factor in the aetiology of this tum our, and groups of cases associated w ith exposure to asbestos have been reported from South A frica (W agner, Sleggs, and M archand, I960), Germ any (KSnig, 1960), the U nited Kingdom (M cCaughey, W atte, and IBmes, 1962; H ourihane, 1964 ; Owen, 1964), and th e U nited State (Selftoff, C hut*, and H am m ond, 1964). Crocidolite, the blue asbestos m ined in South A frica, appears to be particularly carcinogenic in this respect (W agner e t al,, I960). T here is also evidence th at ' tum ours arising in the peritoneum are also related to ire (R eal, 1960 ; Enticknap and Sm ither, 1964 ; H ourihane, 1964}.
In a previous report (fifeQ H S^ay e t of 1962) we described the finding of asbestos bodies in the lungs of 12 o u t of IS
who had died o f diffuse pleural mesothelioma in D etails of th e w orking life w tre available fo r only nine o f these patients, b u t in fo u r of them there was a i ' ' ' of exposure to asbestos. T h is paper describes three further
* Department f Therapeutics tad 1 . ^ t Began. t Department el PathtdacT, tit* <
, the Queen's Unhfertitr t of Belfast.
scried out in Belfast: (1) a study o f the industrial occupation of 42 patients w ith mesotiBHoma of fte pleura and of 42 control patients w ithout m esotheliom a; (2) an investigation of the prevalence o f asbestos bodies in the lungs of patients w ith and w ithout mesothriioma of the pfettm or carcinoma of the lu n g ; and (3) an investigation of the relation between the presence of asbestos bodies in the lungs at death and a history of exposure to asbestos.
1. Industrial Occupation
Patients w ith M esothelioma of the
histories were obtained from the patterns themselves o r, ff the
patients had died, from friends and redtibbouta, Including
those previously reported, 45 cases of mesothelioma of foe pleura had been diagnosed in 1
completed. O nly 4 2 1
of the early patients had died m ore than 15 years i
and no details
"
Control
from m atched controls aefcc departm ent of pathology, I f < _
s th e reootds o f foe.
pleura in the propositus had been made by biopsy foe paired
control was se lected th at patient o f th e same sexand w ithin
1 year of age whoae nam e aim eared cknest to foe nam e a t foe
aifiifiaiUMibiwtia
1965
sam e
"biopsy report be . _ ' spedm ent is f o f foe pleura m foe pn fog poked control p ati
_ ' d 'h i b e o f foe p ared control pa igjm lo t the patients w ith
. _ itiems. ine of the control pat W fittsla d a iR n fsIa
be naced, book was cho:
TeUssg o f Histories.--0< by one of us from a few and from a few of the c
w w ith a special kn
. - J ^ p ^ r jtf o r e . retatves were o te ' ' bOr neighbours knew how M i fo e patient weB enougl it occupation. Although the of work i defect applied , and to control pati
o f Exposure to wishes
1contained crocidoli
: of (h it no attem pt
foal w
tfoe i
_
ir; A definii
e3
_ ft
year o r o f workfog over a period of
os bifore repairer, plum ber, or fi
'R te d te --Y he age, occupational b o f foe 42 i
...... ad of the . A t foe tim e of diagnosis t
T sais L
varied in age from 38 to 88 years (meat
deviation), There were only two wi patiaott w ifo mesothelioma there was asbestos. In eqdtt foe exposure was
24 as lig h t In the 42 paired corn history o f exposure in nine, and in i c te jita t as heavy. T ina different (dbfferenoe* are regarded as significam
the W M o l i w ith heavy exposure ha ' j f Pipe-coKwira o r had often been ex;
confined space* when repairing boilers j g m m g m m t A under light expos
as electricians, plum bers, , m iiaatfor exposed to asbestos dust whe coverers in confined spaces. Shim c fe ss ii^ fo eepoaed to t '
' ' f i b foe e*
"........P l l i i p i 'l i l j i p i l i i p p w
pwgm uwBii
HPnm
%
X -h '
'-`.o ' y%
r i
I
:!
A
,n i (lim ^ ..
-w i^ u tty
&
352 6 February 1965
Mesothelioma rtf Pleura--Elmes et al.
3. Asbestos Bodies and Industrial History
w ith mesothelioma of the pleura were found whereas previously
never more than five patients had been discovered to a single , T o throw light both on the m eaning o f th e presence of
asbestos bodies in lung tissues and on the accuracy o f industrial histories taken after death from relatives, friends, o r neighbours, 20 patients were chosen w ho had died in recent y ean , who had not had either carcinom a of d ie lung o r mesothelioma of the pleura but in whose lung tissues a t necropsy asbestos bodies had been identified. M atched control patients who had neither
ceremon y hot ^meaoth d ion a ^aa d to whose to n s tisanes no
T he tetc8ttoatiaB h is shown th at a history o f m osure to
asbestos during working life was found to abeto to to M tn m te
of patients to whom a firm diagnosis of raescafaeltoma o f f ie
pleura was m ade compared w ith such a history to o stty o n e -
quarter o f those w ithout mesothelioma.
'
.
A study of the occupational histories suggests th at the interval between first exposure to asbestos and th e d to m ay o f -
being selected at th a t patient o f the sam e age and sex whose
nam e was nearest to th at rtf to e propositus to toe " necropsy record book." T he selection of the 40 patients was done by the
the tum our is often long and m ay exceed 40 yearn, and toft exposure may be light and in some instances very transient.
A sim ilar observation was made by W agner et of. (1960).
pathologist (W .T .& M eO X
T he occupational history o f each o f these 40 patients was obtained by one o f th e social workers who visited and qnetttoned relative* end ftiem to T he exposure to asbestos was
T he long latent period m eans th at to e presort incidence o f this disease may have been determ ined by industrial practice
IS to 50 years ago s it aho means th at preventive meatmen undertaken now will n o t affect the
assessed from the todostrial history as heavy, lig h t, o r none by toe h e r tw o a o to en ( P .C E and O .I W .) before toe pathologist revealed w hich were the patients in whom asbestos
betw eep eO an cT ^ yearn eld to B elfast to tn d d lfg to asbestos bodies to their lungs. These older m en started their w otking
bodies had been identified n d w hich were the em m et*.
life between 1905 and 1915. to asbestos bodies were found
Results.--T he results are sum m arized to T able H I. A history of heavy o r light exposure to asbestos was elicited for 14 o f the 20 patients whose lungs contained asbestos bodies,
only to 14% of the younger men (dying between tfa e sg a o f 50 an d 59 years) who had started work between 1915 and 1925. The shipbuilding industry in Belfast was particularly active between 1906 and 1923 and over 1,000 tons of hotter insulation
Table III,--Asto n a l M e in Lungs m i exposure
composition (containing asbestos) was used a y e com pared w ith a m ore usual level of 600 tons a year. By thq tim e ship
1.
TotalNo.
AdhgflbM1,,ulij.-afnssffhlin lii|ig ` a3 5 m bodS notfinwdSMiV
a
w ,___
K tny Usta
tl v
It 4
Hoot si
budding recovered from the slum p and tried to m eet to e needs of toe 1939-45 w ar, the daafltra of handling asbestos w ere ' known and precautions were taken. T h e , difference to frequency of finding asbestos fibres in the lu n g so f m en to the
two age-groups presum ably reflects these changes to in d u strial'
iw tc B w n c n o cm owufoi g n w p n o wiwiiiwwut*1 ! * .
T he shipyards are situated to circum scribed , area on. to e
b u t only tw o of these patients had had heavy etowsure to asbestos. A history of exposure to asbestos was obtained from five of the 20 m atched control patients in whose lungs no
asbestos bodies were seed: only one o f these had h ad heavy exposure. T he differences in history o f exposure to asbestos between th e tw o groups are significant In about a th ird of the patients who have had sufficient exposure to asbestos to have asbestos bodies identified in th eir lungs i t baa n o t been possible to obtain a history of exposure from relatives, friends, o r neighbours, in a S aw h fo r asbestos WyHe* in lung tissue,
confined to the exam ination of tw o to six sections, asbestos . bodies m ay n o t be found although the patient has been exposed to asbestos during his working life.
lough side. T here is one small factory to w hich asbestos is . used in the m iddle of a compact residential area. P lotting on
a m ap the homes of patients w ith roesotbdfionu o f the pleura
does not show eny geographical grouping to suggest contam i
nation of a residential area by asbestos dust either front the
factory or from the shipyards.
.
U ntil recently m ost asbestos used outside the shipyards was
in the form of corrugated roofing. T his was im ported front England, and was usually cut and handled to the open under conditions of good ventilation. T he use of asbestos in m any
industries, and especially in the building trade, is now increasing
{The Tim es, 1964), and this gives rise to anxiety th at there w ill
be an increased incidence of mesothelioma of th e pleura.
It is often difficult to obtain details of past em ploym ent from
a patient, and this is especially difficult if the inform ation sought
concerns work done 30 or 40 years ago. From relatives or S ' neighbours such inform ation is bound to be less accurate, and
Exposure to high concenttations of asbestos dust has long been (mown to cause asbestosis w ith fibrosis of th e lung and pleura, and there is in to condition an increased incidence of carcinoma of the lung (M ercwether, 1949; D oll, 1955). A lthough working conditions have been im proved and the prevalence o f asbesmeis w ith severe fibrasia'of the tong has been reduced, W illiam s and H ugh-Jones (1960) have shown that m any workers in an asbestos factory m ay have disturbed lung function even though no pulm ooaryfibrosia has been detected
this may account for the absence of a history of exposure to
asbestos in some of the patients in whose lungs asbestos bodies
were found, and possibly also in some of the patients w ith
mesothelioma of the pleura. There are also instances to which
asbestos bodies were not found in the lungs o f m en who had
had heavy and prolonged exposure to asbestos. Both these
errors would tend to lead in th is investigation to an under
estim ation of the part played by exposure to asbestos, in the
aetiology of mesothelioma of the pleura.
,
f
iqr cheat radiography.
.
T he present investigation confirm s th at mesothelioma o f toe
pfeui* is another hazard for those exposed to asbestos. A lthough raesotorttam a is a rare tum our it has been possible to
find to Belfast 45 patients With mesothelioma o f toe pleura confirm ed liistotagicaUy by biopsy o r naeropsy. T h e true
prevalence may w ett.b eh igber.becauaethedfaa cal diagnosis b difficult and w ithout biopay o r necropsy the diagnosis m ust often be m issed. In 1963, when physicians and surgeons to this area had become interested in this condition, 13 patients
A history of occupational exposure to asbestns was obtained to 32 o u t of 42 patients w ith mesothelioma rtf to e pleura to B elfast In 42 m atched control patients o f to e *Mw ege and so t a history o f exposure was obtained to to f.ato e.
Asbestos bodies were found a t necropsy to th e lungs o f 14 27% o f men aged 50 to 69 dying recently of diseases other than
;i
6 February 1965
carcinom a o f toe bronchus an Asbestos bodies were found it
A history o f an todastrial
ab o u tthreoquanen of ]
I t is concluded tin t there asbestos, even though it may hav previous, is an im portant factor i of the pleura. T his conclusion of the increasing commercial us
Mrs. Yvor untiringly < from patiei We are grateful to for their help in search who have helped by re to thank Dr. Merrett, of the Dep
Serum Adenosine
Brit, med.J., 1968,1, M3-M1
T he ability o f m ost tissues o adenosine to inosine and ammon adenosine deam inase. T his cn blood and serum by Conway an
A fter the dem onstration of deam inase activity in tum our-b 1957) and to hum an p atien t (Lem ansky and Seeikb, 1958) adenosine deam inase activity in i a variety of malignant and non and Benz, 1962). T he last of tt ficant but non-diagnostic ele* deam inase activity to the rnalig hand, die highest activities in t patients w ith infectious mononu.
T he present report concerns adenosine deam inase activity in : and w ithout jaundice, and it has non is of value in distinguishii obstructive and hepatocellular ca
Materials and Four categories of patient wet Group ri.--This group consisted
to elective was males 34 and fen to 79 years.
- 1 lhJl'll!JUiiJp|ip P !j p |ILl'l|ii:ji I..L
mms I p f fl p l p
----- V .'.
s- v - > f t p . - ' - ' " - t r & K y . ; * '
1
IlllllliiliiitilllIIIITIIIII'-1 ^
Mm w I mkiw
| p la n s w av found whereas previously S atis had been discovered in a angle
jsbtfwn th at a history of exposure to
life was found in about three-quarters Inn diagnosis of mesotheHoma o f the led w ith such a history in only onemesothelioma.
josure to asbestos and die discovery o f g and m ay exceed 40 years, and the p d in some instances very transient, i mgde by Wagner et of. (I960),
i means font d ie present tnddence of ta t determ ined by jntfoatriri ptactiee also means th at preventive measures , affect the incidence for m any years.
' Ixmt a quarter o f m en dying recently old in .Belfast should have asbestos 'hese older m en iterte ti then working
' ' , 15- B ut asbestos hodiea were-found , . ;er m en (dying between the ages o f JO
started work between IM S and 1925. . ry in Belfast was particularfy active
nd over 1,000 tons of boffer insulation asbestos) was used a yew compared if 600 tons a year. By the, tim e ship . . . . . the slum p and tried to meet die needs . : dangers of handling asbestos were ' * i were taken. T he difference in - istos fibres in the lungs of m en in the f i ' >ty refiects these changes a t fodustrial
rated in a circum scribed area on 'th e te sm all factory in whicn asbestos is compact residential area. P lotting on ents With mesothelioma of the pleura uphical grouping to suggest cootatni-
by asbestos dust either from the
used outside the shipyards was
roofing. T his was im ported from
cut and handled in the open under
ion. T he use of asbestos in m any
the building trade, is now increasing
gives rise to anxiety that there will
jo f mesothelioma of the pleura,
jbtain details of past employment from
iiafiy difficult if the inform ation sought
OT 40 years ago. From relatives o r ition is bound to be less accurate, and h absence o f a history of exposure to
Indents in dure lungs asbestos bodies
|y also in some of the patients w ith
'jra. There arc also instances in which
found in the lungs of men who had
exposure to asbestos. Both these
th is investigation to an under
by exposure to asbestos in jh e j
the ylrera.
t
exposure to asbestos was obtained vrath mesothelioma of th e pleura la am tw rfjpMfent of the same age and
a t necropsy in the lungs o f 14sg recently of diseases other than
6 February 1965
Mesothelioma of Pleura--Elmes et al.
unJSnSumxu. 353
carcinoma of the bronchus and mesothelioma of th ep leu ra. Asbestos bodies were found in the lungs of about 20% of patientx dying w ith carcinoma of the lung. They were found in m ore than 80% of men dying of mesothelioma of the pleura.
A history o f an industrial occupation w ith exposure to asbestos ire* obtained from relatives, neighbours, o r friends o f about three-quarters of patients in whom adustos bodies were found in the lungs a t necropsy. Such a history was obtained
for one-quarter o f patients in whom asbestos bodies were not found in the lungs a t necropsy.
I t is concluded th at there is evidence that exposure to
asbestos, even though it may have been transient and m any years
previous, is an im portant factor in the aetiology of mesothelioma
of the pleura. T his conclusion gives cause for anxiety because
of the increasing commercial use of asbestos.
We wish to thank Mrs. Yvonne Dudgeon and Mrs. Marion Simpson who worked untiringly with patience and tact to obtain occupational histories from patients or their relatives, friends, or
neighbours. We are grateful to the records officers of Belfast
hospitals for their help ia searching out old notes and to many colleagues who have helped by referring patients to us. We wish to thank D r. M errett, of the Department of Social Medicine, for
statistical advice. We are indebted for gran to the Stewart Friar Fund administered by the Faculty of Medicine of Queen's Univer sity, the British Empire Cancer Campaign , the Northern Ireland Hospitals Authority, the Royal Victoria Hospital Endowment Fund,
and the Medical Research Council.
Kc U n S / t B rit* /< MWMlfft A m I fc B i*
nap, J. B , and Smither, W. J. (1964). Ibid., 21, 2,
e, R. (1932). Lancet, 1, 'n i l .
''
te, M.
Cancer. 10, 298.
Hurihaoe, D. (TO. 09*4). Thorax, 19, 268.
" ' B. 0960). rawer, 2, 1211.
* (I960), drefc. Gwtarbtpmk. Gexxerbehyg., 18. 159.
Mcrawcit.he*r?, -E. -R..A- . ( -- -
R~epo'rBt iot""f, tmheadC. Jhie2f,in1s1p9e7c. tor of
faetones tar the year 1*47. H.M.S.., London.
Owen. W. 6 . (1964). Bm . m ed-J., 2, 214,
Seffinff) I. Churg, J., and Hammond, E. C. (1964). J. Amar. mad.
dm l t t , 22.
The Times (London), 5 March 1964, P. 17, col. 7.
Wagner, J. C , Monday, D. Bn and Harington, J. S. (1962). J. Path.
Pact., 84, 73.
----- Sfe^s. C. A , and Marchand, F. (I960). Brit. J. indum . Med., 17,
W itlrenu', R .. and H ugh-Jonea. P. (I960). Thorax, IS, 109.
Serum Adenosine Deaminase in the Differential Diagnosis o f Jaundice
D. M. GOLDBERG,* M .B., c h .b., b.sc.
Brit, merf.y., 1965,1, 353-355
T h e ability o f roost tissues of higher anim als to convert adenosine to inosine and ammonia is due to a specific enzyme, adenosine deam inase. T his enzyme was detected in vvhole blood and serum by Conway and Cooke (1939).
A fter th e dem onstration of elevated serum adenosine deam inase activity in tum our-bearing anim als (Straub et 1, 1957) and m hum an patients w ith bronchial carcinoma f l .etnansky and Seelich, 1958) a study was m ade of serum adenosine deam inase activity in hum an patietus suffering from a variety of m alignant and non-m alignant diseases (K oehler and Benz, 1962). T he last of these authors reported a signi ficant b u t non-diagnostic elevation of serum adenosine deam inase activity in th e malignant group. O n the other hand, the highest activities in the series were found among patients w ith infectious mononucleosis and hepatitis.
T he present report concerns an investigation of seruru adenosine deam inase activity in a large group of patients with and witiwroi Jaundice, and it has been found th at the estim a tion is o f value in distinguishing betw een Jaundice due to obstructive and hepatocellular causes.
.,
Materials and Methods
Bbur categories a t patient were nudied.
Gnmp A --This group consisted of 52 healthy blood donors and M & ata far to elective operations for henriae and varies vrint. Sex farirenfo ret mates 34 and females 19, and ages ranged bom I r o n yens. '
Group B.--This group consisted of SO patients suffering a variety of primary diseases, in the course of which the clinician suspected hepatic complications, but in whom neither Jaundice nor any other clinical or laboratory parameter of such complications was detected after careful investigation. The cases were distributed as follows:
cancer 2 2 ; myocardial infarction 4 ; congestive cardiac failure 4 ; reticuloses 4 ; muscular dystrophy-3; miscellaneous gastrointestinal disorders 1 0 ; chronic alcoholism 3.
Group C.--This group consisted of 58 jaundiced patients in whom
the cause was dearly obstructive. Cases with radiological evidence
of stones In the bfiiary tract, or of hepatomegaly in known cancer
cases, were included if the biochemical data were diagnostic. In all
other cases within this group (48) the diagnosis was established
at laparotomy or necropsy. In 30 cases the obstruction was asso
ciated with malignancy. The remainder were cases of cboM ithiitis
with or without assoaated cholecystitis..
.
Group D.--This group consisted of 55 jaundiced patients in
whom the cause was clearly hepatocellular. This was established
by histological examination in 28. The remainder were cases of
Infectious hepatitis and cirrhosis showing the classical dhdcil and
laboratory features of there conditions, together with four cases of
acute jaundice following administration of known hepatomxic drugs
(cblotpromaztne, two cases; pom-aminosalicylic add, two cases)
subvfciing on wfthdrawal of the suspeaed agent. In this group there
ram 26 caret of portal cirrhosis, 13 cases of infectious hepatitis,
4 cases of btlisry cfohosis, and 6 cases of mncdlaneous subacute or
chronic hepatocellular affections.
.
'
S tem s adenosine deam inase activity w as m easured by a specoopbotom etric m ethod based on th a t o f Solomon (i960). T h e optical density o f a solution containing 20 pg. of adenonin c per m l o f 0 .1 M phosphate buffer pH 7 was read
a t 265 t n p i a a 1-cm. light path im m ediately after addition of aerom (0.05 roL/3 m l. buffer-substrate m ixture) and again a fte r incubation a t 37* C for e n e .h c te th e spectrophotom eter being set a t zero, using 0.05 m l. o f serum in 3 m l of 0.1 M
remW'WWiWBWW1' 4
* aimrnmm JI ,JInmniliww iw m aiw P t e f i W * . '
! T
k ' vi
J