1034

That epidural analgesia need not change the type ofdelivery achieved is not the only criterion againstwhich the technique must be judged.Many women wish to contribute to their own de-

livery, and to these epidural analgesia provides thesatisfaction of achievement without the usual accom-

panying discomfort. Indeed, cooperation is enhancedby the absence of central sedation and distraction bypain.

If the technique was accompanied by a hazard tomother or baby the procedure could not be justifiedin normal obstetrics. Complications of the procedureitself have been few and minor. However, to achievethese results careful attention to detail in techniqueand observance of the usually accepted contraindica-tions to the procedure have been important.The most distressing maternal complication was

post-spinal headache from dural puncture. Severeheadache was uncommon, and seems a small price topay for the superior analgesia in the vast majority ofpatients. Hypotension was the most common maternalcomplication, but it did not contribute to maternal

morbidity.Fetal distress was diagnosed clinically in 0-8% of

patients in association with an episode of maternalhypotension. In one patient with a fetus already atrisk, hypotension from epidural analgesia may haveproved the final insult to the fetus.With this one exception there has been no evidence

of harm to the fetus as judged by Apgar scores, peri-natal-mortality rates, or detailed consideration of thecase-histories of stillbirths and neonatal deaths.While there is no doubt in our minds that in many

patients the second stage is a little longer than if thistechnique had not been used, we doubt the signifi-cance of this extension in the absence of active expulsiveefforts. Perhaps a more detailed clinical and bio-chemical study will help us decide whether patienceand normal delivery or elective forceps delivery whenthe patient is ready for delivery is the better policy.For the moment we make no recommendation onthis point. However, we feel that the use of epiduralanalgesia need create no more than minor changes inobstetric practice. The good quality of pain reliefafforded by this technique, despite its potentialdangers, does not preclude normal delivery and thetechnique deserves to be more widely used for painrelief in normal obstetrics where personnel of sufficientskill and experience are available to provide thisservice with safety.

We thank the honorary medical staff and the medical superin-tendent for their support and assistance with this work, andMiss D. de Luce in maintaining the records. The record keepingand analysis of data was made possible by a grant from AstraChemicals Pty. Ltd.

Requests for reprints to be addressed to N. P., Women’sHospital (Crown Street), Crown Street, Surry Hills, Sydney2010, New South Wales, Australia.

REFERENCES

1. Moir, D. D., Willocks, J. Br. med. J. 1967, iii, 396.2. Paton, A. S. Med. J. Aust. 1966, ii, 449.3. Murray, J. C. Personal communication.4. Doughty, A. Br. J. Anœsth. 1969, 41, 1058.

FIVE-YEAR ANALYSIS OF PROTECTIVEISOLATION

BERYL JAMESONJULIA LYNCH

D. R. GAMBLEH. E. M. KAY

Royal Marsden Hospital, Sutton, andPublic Health Laboratory,

West Park Hospital, Epsom, Surrey

Five years’ experience in the protectiveSummary isolation of leucopenic patients isanalysed. The total period encompasses 1286 patient-weeks, and includes 459 patient-weeks in which thegranulocyte-count was less than 500 per c.mm. Iso-lation can largely prevent the acquisition of staphylo-cocci, of some gram-negative organisms, and of somecommon respiratory viruses. The relative importanceof sterile air, fomites, and food is considered and acomparison is made of cubicles and plastic tents forisolation. Analysis of serious and fatal infections showsthat exogenous organisms can, through isolation, bevirtually eliminated as a source of risk, thus increasingthe chances of recovery or remission from disease.

Introduction

WE have previously described the design and functionof a ward built for the isolation of patients prone toinfection. 1, Experience extending over five years nowallows some assessment of the efficiency and value ofthe unit. Furthermore, patients have been isolatedeither in cubicles or in plastic tents,3 and some com-parison between the two methods can be made.The procedures and practice, as initially devised,

have been followed except for a few minor modifica-tions dictated by experience and referred to below.One aspect of procedure, which will be the subject ofa separate report, is the use of intestinal antibiotics.Within the past four years suitable patients have beenrandomly allocated to a regimen of neomycin, colistin,and amphotericin B or to a control ’’ no intestinalantibiotics " regimen. So far no significant differencesin rates of infection have been observed, but sincethese antibiotics may influence the assessment of iso-

lation, we should mention here that for 24 admissionsout of the total of 175, non-absorbable antibioticswere given for at least part of the patients’ stay inisolation.The main indication for isolation of the patients was

actual or anticipated leucopenia. Isolation was con-tinued until the risk was judged to have passed or untilit seemed that all treatment of the disease (mostlyacute leuksemia) was ineffective. Many leucopenicpatients were therefore freed from isolation in theterminal stages of their illness, a practice which wasfacilitated by the ward design, as it was not necessaryto transfer the patient from his isolation cubicle.The efficacy of isolation is here examined by com-

paring the rates of infection and colonisation by variousmicroorganisms in isolated patients with those foundin patients in other circumstances.

Patients and Methods

The cases treated and the duration of isolation are shownin tables i and II. In the tables and throughout the textthe abbreviations A.L.L. and A.M.L. are used for acute

lymphoblastic leuksemia and acute myeloid leukaemia;

1035

TABLE I-ISOLATION (IN PATIENT-WEEKS)

TABLE II-ISOLATION (IN PATIENT-WEEKS ANDNUMBER OF ADMISSIONS) IN RELATION TO DIAGNOSIS

respectively. Most of the patients with acute leukaemiareceived intensive therapy causing myelodepression or

were leucopenic as a direct consequence of the disease.Most of the cases of idiopathic or drug-induced hypoplasiawere severely leucopenic. The miscellaneous group weremainly patients with solid tumours undergoing cytotoxicdrug therapy.The period of risk is indicated very approximately by

the sum total of the time at which the granulocyte-countwas below 500 per c.mm.; this is the level most commonlycited in this context, although there is a significant risk athigher levels. Table III shows that a total of 3214 days(459 weeks) was spent by patients in isolation having agranulocyte-count of under 500 per c.mm. (i.e., rathermore than a third of the period analysed).

TABLE III-PERIODS WITH GRANULOCYTE-COUNTS

500 PER C.MM. (IN DAYS)

All patients were swabbed for bacteriological examina-tion on admission to isolation and weekly thereafter.Swabs were taken from the nose, throat, hands, hair, ears,and perineum; samples of faeces and midstream urinewere also cultured. The stool cultures were repeatedtwice weekly throughout isolation.Nose, hand, and hair swabs were plated on to phenol-

phthalein phosphate agar and examined only for thepresence of Staphylococcus aureus. The remaining speci-mens were cultured on conventional media, and the micro-flora were identified by the methods of Cowan and Steel.4 4At least the genus of each organism present was recorded.The primary purpose of these investigations was to notechanges in the individual patient’s flora (e.g., dispropor-tionate amounts of Candida in throat swabs, colonisationof the skin by gram-negative bacteria, or the presence infaeces of marker organisms which could be evidence ofcross-colonisation among the patients).

Staphylococcal AcquisitionThe information obtained from nasal swabs was used

to compare the rate of apparent acquisition of staphylo-cocci by isolated patients with patients in another part ofthis hospital and with other published data. All coagulase-positive staphylococci were phage-typed by the CrossInfection Laboratory of the Central Public Health Labora-tories, London N.W.9. Any Staph. aureus appearing forthe first time in the second or subsequent swabs and anychange of phage-type was regarded as an apparent acquisi-tion.5

Acquisition of Gram-negative BacteriaAll pseudomonads, from whatever source, were phage-

typed and serotyped at the Central Public Health Labora-tories, and the identity of each organism was checked againstthat of pseudomonads obtained from other patients andin the course of routine checks on the environment-e.g.,from sink and handbasin outlets in the " dirty " areas ofthe ward.

In addition the normal procedures of identification ofnonlactose-fermenting bacteria in fasces revealed some

biochemically atypical coliforms which could be used as" marker " organisms.

Virological ProceduresSpecimens for virus isolation were collected from all

patients at the beginning and end of each period of isolation,and from pyrexial patients during isolation. Pooled noseand throat swabs and specimens of fxces were usuallytested for virus within a few hours of collection, but in afew instances they were stored at +4°C for up to 24 hoursbefore testing. All specimens were inoculated into culturesof secondary monkey kidney, hela, and primary humanamnion cells, and by the intramuscular and intracerebralroutes into day-old suckling mice. Nose and throat swabswere also tested in human diploid cells (WI-38 strain).Virus isolation and identification techniques were thosedescribed by a Medical Research Council working-party. s

Specimens of serum were also collected at the timesspecified above, and additional " convalescent " specimenswere obtained from febrile patients 2-3 weeks after theonset of pyrexia. Sera were tested against a range of viral,rickettsial, and mycoplasmal complement-fixing antigensin plastic trays by the method of Bradstreet and Taylor. 7The antigens were kindly supplied by Dr. C. M. P.

Bradstreet, of the Central Public Health Laboratory,London N.W.9. Sera were screened at a dilution of 1/4against the cytomegalovirus (c.M.v.) antigen, and at 1/20against all other antigens. The methods used for neutralis-ing antibody estimations were as described by Grist et al. 8

Results

Staphylococcal AcquisitionThe rate of apparent acquisition of staphylococci in

isolated patients is compared with that found in

patients in another part of the hospital and with otherpublished data in table iv. The rate in isolation is

very much lower than in the other situations, and ifaccount is taken of the probability that some are notacquisitions at all, the proportionate reduction iseven greater. If, for example, the pseudoacquisitionswere 0-5 per 100 patient-weeks in all series then thetrue acquisition-rates would be 5-9 (6-4 -0-5) in Par-ker’s study 5 and 0-8 in ours (1.3-0.5). The propor-tional reduction in acquisitions would then be not6-4/1-3 (5-fold) but 5-9/0-8 (72-fold).

Further data relate to the rate of carriage of staphylo-cocci by attendants. In 1967 and 1968 all attendants

1036

TABLE IV-APPARENT ACQUISITIONS OF STAPHYLOCOCCI

who entered the cubicles (nurses and doctors) anddomestic staff who worked in the kitchen and corridorbut did not enter the cubicles were examined fornasal carriage by weekly swabbing.A nasal staphylococcus was found at least once in

50% of the staff in 1967 and in 29% in 1968, and ofthose who could be tested for 4 weeks or more about a

quarter had retained the same phage-type. An attemptduring this period to reduce this rate with a nasalcream containing neomycin was unsuccessful, and forthis reason and because of the potential hazard ofsensitisation it was abandoned. At the same time

regular swabbing of staff was discontinued in favour ofthe equally informative and less laborious ad-hoc

investigation of acquisitions and infections.

Acquisition of Gram-negative BacteriaOn two occasions biochemically atypical " marker

coliforms appeared in the stools of several patientssimultaneously, and investigation of the possible sourceon each occasion revealed a flaw in kitchen procedure.The use of dairy cream was implicated once, and thesecond time the probable source was considered to bean insufficiently cooked Christmas turkey.The pseudomonads provided more precise informa-

tion. One acquisition in the mouth of a child who hadbeen in isolation for many weeks was unequivocallytraced to the water used to make up mouth washes inthe pharmacy. Sterile water was thereafter used forall oral medicaments.

In 1970 a small epidemic of cross-colonisationoccurred. Over a period of 6 weeks an identical pseu-domonas appeared in the stools of four isolated patients.A fifth patient, not in isolation, who had severe

diarrhoea, had been carrying the same strain for 2months previously. A pseudomonas of the same phage

TABLE V-PSEUDOMONAS CARRIAGE AND ACQUISITION

type and serotype had been present in the environmentintermittently since 1967; and though it had not

proved possible to eradicate it completely from areassuch as sinks, it had never previously been found in anypatient. During investigation of the outbreak the sameorganism was found in the fasces of one nurse. Therewas no other apparent route of dissemination, but it isnot possible to say with certainty whether the nurse,though experienced and conscientious, was responsiblefor its spread or had merely acquired the organism inthe same way as the patients.

TABLE VI-VIRUSES RECOVERED FROM PATIENTS

BEFORE AND DURING ISOLATION

* 55 separate pyrexial episodes were investigated.

The cook was also found to be a carrier at this time,though of a different strain of pseudomonas, but pseu-domonads have on no occasion been cultured from

prepared food.There have been no other episodes in which there

was evidence for a common origin, but there havebeen a few instances of apparent acquisition of pseudo-monads by patients during isolation.Table v shows the proportion of patients found to be

carriers on admission and the proportion from whomthe organisms were cultured at a later stage of iso-lation. In those patients in the " possible column,it appeared not less than 2 weeks and most commonlyabout 4 weeks after isolation. Before 1970 none of the

apparently acquired pseudomonads was identical withany other found in the ward at the same time or forseveral weeks beforehand. It can be seen that, whereasthe carriage-rate on admission is similar to that foundby Shooter et al., there is an obvious difference in therate of acquisition-i.e., 8% compared with 21 o ifpatients alone are considered or with 32% if acqui-sition of each new strain of pseudomonas is takeninto account.

1037

Virus Isolations

The viruses recovered from sixty-nine patients onadmission to isolation are shown in table VI. Herpes-simplex virus (H.s.v.) was isolated from four patients,in two of whom a 4-fold or greater increase in antibodytitre to H.s.v. was subsequently detected, indicatingrecent primary H.s.v. infection. The other two patientsshowed nc significant change in H.s.v. antibody titre,and the presence of virus presumably indicated re-currences of latent herpetic infection. Five patientswere carrying picornaviruses, but, since these virusesdo not normally give rise to latent or recurrent infec-tion, recent infection may be assumed. Thus seven ofthe sixty-nine patients (10%) had apparently sustaineda recent virus infection before admission.

Forty-five patients were investigated during pyrexialepisodes which occurred during 55 separate periods oftreatment in isolation, but only three viruses wereisolated (table vi). H.s.v. was recovered from one

patient in whom this virus had already been demon-strated in an admission specimen. Poliovirus type illwas isolated from a patient 31 days after admission.This patient, although pyrexial, showed no evidence ofclinical poliomyelitis; the cerebrospinal fluid was

normal and tests for complement-fixing and neutralis-ing antibodies to poliovirus types I, II, and III showedno evidence of recent infection. Viral culture and

antibody tests on the staff and other patients in thewards were all negative. Picornaviruses are usuallyexcreted for several weeks and occasionally for 2-3months, and it is possible that this virus was presentbefore admission. In view of the failure to find a sourceof infection among the contacts, and the absence of an

antibody response or clinical poliomyelitis in the

patient, this is perhaps the most likely explanation ofthe presence of this virus. Coxsackievirus type A4 wasisolated from a patient 10 days after admission, and thispatient developed a stomatitis on the eighth day ofisolation. The incubation period of coxsackievirus isusually 3-5 days, with a range of 1-14 days. Again,therefore, it is difficult to say whether this patientacquired his infection either just before or just afteradmission.

TABLE VII-SERUM COMPLEMENT-FIXING ANTIBODY STUDIES*

* 93 patients and 114 periods of isolation were studied for all organismsexcept cytomegalovirus, where 76 patients and 91 periods of isola-tion were covered.

t " Rising titres " refer to 4-fold or greater increases in complement-fixing antibody titres between specimens of serum collected onadmission to and discharge from isolation.

I

Viral Serological Tests (table VII)Some of the ninety-three patients studied were

isolated on more than one occasion and, in all, 114" patient isolations " were investigated by complement-fixation tests on serial sera.

Apart from c.M.v. infections (see below) a significantrise in titre (4-fold or greater) was detected in fourteenpatients, but in twelve of these antibodies were alsopresent in the admission specimens of serum. In oneof the two cases with rising titres against H.s.v. therewere localised herpetic lesions, but in none of theremaining cases was there any evidence of activedisease. The reason for these rising titres is not at onceapparent since some patients had had mumps or

measles a long time before admission.In most viral infections antibodies are not detectable

for 2 weeks or more after the date of infection; hence,rising titres in patients who were seropositive onadmission can probably be ascribed to infection beforeadmission. Two patients had rising titres of adeno-virus antibody which was not detected in their ad-mission specimens. Neither patient showed any clini-cal evidence of respiratory infection, and, althoughthey could have been incubating virus on admission,the possibility of subclinical infection during isolationcannot be ruled out.These serological tests, therefore, revealed only two

infections which could have occurred during isolation,and, since the patients studied represented a total

period of observation of about 900 patient-isolation-weeks, this suggests the low infection-rate of oneinfection per patient per 450 weeks in the isolationunit. By comparison, if the 12 rising titres in patientswho were seropositive on admission can be taken as ameasure of virus infection in, say, the preceding 4weeks, our patients would have acquired 12 infectionsin 452 patient-weeks before isolation, or 1 infection

per patient per 38 weeks.Virus isolation and serological results, taken to-

gether, provided evidence of recent infection in twenty-three patients on admission to the ward. If this can betaken as a measure of the virus infection rate during,say, the 4 weeks preceding admission, it would indicatea virus-acquisition rate of 6-5 per 100 patient-weeks.In the normal population acute virus illnesses occurat the rate of about 7 per 100 patient-weeks (e.g.,Fox et al. 9), but using current virological techniquesit is possible to implicate a virus in only about half ofsuch illnesses. 6-5 per 100 patient-weeks is therefore ahigh virus-acquisition rate and probably reflects theincreased susceptibility of leukasmic patients. In

contrast, we found evidence of virus infection in onlyseven patients during isolation, representing an acqui-sition-rate of 1-1 per 100 patient-weeks.

CytomegalovirusCytomegalovirus antibodies were estimated in serial

specimens of serum from seventy-six patients during91 separate periods of isolation. Rising titres weredetected in eight patients, five of whom were sero-

positive on admission and had presumably beeninfected before isolation. The three patients withrising titres who were seronegative on admission mayhave been infected during isolation, but they showedno clinical evidence of infection other than pyrexia at

1038

the time, although one of them subsequently de-

veloped pneumonitis.Although three c.M.v. infections during 91 periods

of isolation (648 patient-isolation-weeks) suggests a

considerably lower infection rate than that before

isolation, it might still indicate a failure of the isolationprecautions if blood-transfusion were excluded. How-ever, the pattern of antibody response to c.M.v. infec-tion differs from that in most other virus infections,and a rising titre may not necessarily imply a recentinfection. In one of our patients serial antibody titresrose, fell, and then rose again; Sullivan et al. 1-0 havealso reported this pattern. Moreover, titres may fall,sometimes to undetectable or questionable levels (1/2),and the absence of antibody may not always imply theabsence of previous infection. After infection by therelated H.s.v., the virus persists in a latent form, andintermittent reactivation in response to a variety ofstimuli may lead to intermittent viral excretion. Both

primary herpetic infection and reactivation may befollowed by an increase in antibody titre, but theprimary response is of greater magnitude than thatafter reactivation. c.M.v. antibodies may follow a

similar pattern, but since in one of our patients asubstantial increase in titre from 1/4 to 1/256 wasknown to have been preceded by an earlier significantrise and decline, the magnitude of a c.M.v. antibodyresponse may not distinguish between primary infec-tion and reactivation. We cannot, therefore, saywhether the c.M.v. antibodies found resulted fromrecent primary infection or reactivation of previousinfection, or were perhaps non-specific or anamnesticeffects; this problem is being further investigated.

Discussion

It is generally accepted that leucopenia predisposesto infection, and there is good evidence that granulo-cyte-counts below 1000 per c.mm. carry increasinglyhigh risks of serious infection." Isolation, whenleucopenia is present or is anticipated, is, therefore, arational procedure, but its efficacy in practice has yetto be measured and its value proven. Most of the

published work hitherto is based on an insufficient

period of study (anything less than about 200 weeks isalmost meaningless) or gives inadequate details aboutpatients and methodology for a precise evaluation (seemonograph on Aseptic Environments and CancerTreatment 12 for the most comprehensive data, andthe paper by Winner et al.13).Does isolation prevent the acquisition of foreign

organisms; what are the most important componentsof an effective isolation regimen and what is their

cost; and what is the benefit to the patient of isolationin terms of a reduced rate of infection and mortalityand in terms of the ability to receive, without interrup-tion, a given course of cytotoxic therapy ? Partialanswers can be given to some of these questions.The rate of staphylococcal acquisition can be re-

duced, perhaps to about 1-0 per 100 patient-weeks,13and the transfer of pseudomonas can be prevented tosome extent. Furthermore, it is our impression thatthe flora of the bowel does not change very significantlyin the absence of transfer of potential pathogens viathe food. Infection by the common respiratory and

other viruses can also be greatly reduced despite thefact that nurses frequently have to continae at workduring minor respiratory infections.

Identification of the most important parts of theisolation regimen depends upon knowledge of theroute of infection and acquisition under normal cir-cumstances and upon tracing the source of the organismwhen the isolation regimen has apparently failed:

(1) Air filtration, air conditioning, and ventilationmust first be considered, for they figure prominently inthe design and cost of isolation units. Data from a burnsunit 14 suggest that airborne contamination is of minor

importance compared with acquisition of organisms byfomites and direct contact, and that in a general wardisolators with filters are only marginally better at excludingorganisms than those without filters. However, thesituation is different for a leucopenic patient, in whom therespiratory tract is an important portal of entry for potentialpathogens and who may be susceptible to viruses and fungiwhich do not affect the patient with burns. It is, perhaps,significant that no case of pulmonary aspergillosis, crypto-coccosis, or pneumocystis occurred in isolated patients,whereas during the same period such infections were

encountered elsewhere in the hospital. In any event,given that a barrier is necessary to exclude human-borneorganisms, some sort of ventilation is needed and air-

conditioning is desirable for the comfort of both patientand attendants; furthermore, constant humidity and

temperature may diminish the rate of respiratory infection.It may be doubted, however, whether air-filtration isneeded. If a clean air supply can be obtained from outsidethe building, pathogens other than fungal spores are

probably virtually absent. Hitherto our practice has beento filter all air to 0-5 {., and this involves a moderatelyexpensive filtration plant. In a new unit now under con-struction a system of filtration to 5 V. only, which is cheaperboth to install and to run, will be evaluated.

(2) The role of fomites in transfer of organisms is alsodifficult to assess. At first sight it seems that the staphylo-coccal acquisitions in the isolation tents came about

through the transfer of objects to the patient, but perfora-tions in the fitted gloves are perhaps an equally likelyroute. These and the other true acquisitions happeneddespite a comprehensive and rigorously enforced schemeof sterilisation and disinfection. However, oversights-

TABLE VIII—SEPTICÆMIAS AND OTHER SERIOUS

INFECTIONS* IN ISOLATED PATIENTS

* One staphylococcal lung abscess; one E. coli meningitis.t Including 2 generalised Candida infections following prolonged

antibiotic therapy for septicaemia.3 other patients died with positive blood cultures within a week of

admission.

1039

the pseudomonas in the mouth-washes isa glaring example-and errors of tech-nique will always be liable to occur.

Perhaps the main argument for sterilisingall objects, even though the risk from suchitems as books and letters is probablynegligible, is that it helps to enforce a highstandard of aseptic practice. But certaineconomies could probably be effected.For example, simple clean launderingand the use of bed-pan washers which alsodisinfect could be substituted for auto-claving if the risks of recontaminationcould be eliminated.

(3) The problem of sterile food re-quires particular attention because of therisk of gram-negative septicaemia fromacquired organisms, especially pseudo-monas. Comparison of our data withthose of Shooter 15 supports his con-

clusion that food is a significant factor inthe transmission of gram-negative bac-teria to hospital patients, and the onlyfeasible alternative to sterile food is

prophylaxis by non-absorbable antibio-tics. However, the cost of providing asterile but varied diet (an extra E2 perpatient per week) is not a major compo-nent of the total cost, and only a demon-strable superiority of an antibiotic regimen-and there are many different factors, including cost, to betaken into account-would suggest its abandonment.

Benefits of IsolationBecause the leucopenic, immunodeficient patient

may succumb to infections by endogenous organisms,especially those which normally inhabit the alimentarytract, it can be argued that isolation is only of marginalvalue in preventing the proportion-and perhaps it is asmall one-of infections due to exogenous organisms,or in deferring an inevitable septicaemia from onesource or another. There is some force in this reason-

ing, but at present there is insufficient evidence for adefinite conclusion.

In seeking an answer we have analysed (intable vill) serious infections and deaths in iso-lation in our unit during the past five years todetermine, as far as is possible, the source ofinfection and to assess whether, at the time ofthe infection, there was any substantial hopeof a remission or of recovery of the bone-marrow. Both these assessments are inevitablyrather imprecise. " Still treatable " diseaseindicates that in A.L.L. less than six drugs hadbeen tried and found ineffective, and in A.M.L.that less than 6 weeks of cytotoxic drug treat-ment had been given, and in hypoplasticanaemia that the bone-marrow had shown nosign of recovery despite treatment over a periodof at least 3 months. Excluding three fatal

septicsemias within a week of admission to

isolation, there were six deaths which occurredwhen recovery was still possible. In three ofthese a previously acquired organism was

involved (2 pseudomonads present before iso-lation in two cases of hypoplastic ansemia andvaricella acquired before admission in a patient

Fig. 2-23-year-old female with A.M.L.: blood picture.

with A.L.L.); in three others the organism was probablyendogenous (Escherichia coli septiceemia in a case ofA.M.L., multiple organisms in a case of hypoplasticanasmia, and Klebsiella septicxmia in a case of hypo-plastic anxmia with bronchiectasis).There were three septicaemias from demonstrably

exogenous organisms: two in patients with A.M.L.

resistant to cytotoxic therapy were fatal, and onestaphylococcal septicaemia was successfully treated andthe patient went on to achieve a complete remissionfrom A.M.L. There were, therefore, no deaths due toexogenous organisms in patients who might haveresponded to treatment. although a certain element of" luck " is evident.

Fig. 1-39-year-old male with idiopathic bone-marrow aplasia: blood picture.

1040

The importance of preventing infection increases inproportion to the chance of successful treatment of theblood-disease. Spontaneous recovery can happen inapparently hopeless cases of hypoplastic anaemia, andisolation may be life-saving. Fig. 1 shows a chart ofsuch a patient admitted with staphylococcal septicxmia.This was successfully treated and he remained in aplastic tent for 3 months while his granulocyte-countgradually improved and his platelet transfusion re-quirements diminished. 2 years later he is alive and

leading a normal life.In A.M.L. the chance of remission seems to depend

very much on the ability to administer sufficient treat-ment at the onset without actually killing the patient.Fig. 2 illustrates what can be achieved provided thepatient can be carried through the period of marrow-depressed risk, in this instance 6 weeks. Thereafterthe same courses of treatment could be continuedwithout the need for isolation.

In A.L.L. the risk during remission induction is

usually less than in A.M.L., but it certainly exists,especially in those cases which require drugs otherthan prednisone and vincristine to achieve a remission.What is needed is a comparison of enough patientsgiven the same treatment, whether or not they wereisolated. This may be possible for A.M.L. and A.L.L.regimens in the Medical Research Council clinicaltrials. A cost-benefit analysis would then be possible,taking into account both the morbidity and mortality,and also the ability, given isolation facilities, to adhereto the protocol of treatment despite leucopenia.Cubicles and Tents

Enough experience has now been gained to makesome comparison between cubicles and plastic tents.The bacteriological data show no significant differencebetween the two, despite the theoretical advantage thata tent forms a more complete physical barrier. Bothmethods afford protection from exogenous organisms,and the comparison really rests upon their conveni-ence, cost, and acceptability to the patient. Both

systems are well tolerated by most patients, but chil-dren under 10 cannot be cared for in a tent and one ortwo adults have complained of claustrophobia. Others,however, who have experienced both systems, pre-ferred the tent.

Nursing is easier in cubicles than in tents, but in asystem where several tents could be grouped in a largeward the ability to go directly from one patient toanother without gowning and scrubbing, &c., mightresult in a greater economy of nursing-time, which isthe biggest single item in the cost of isolation.We intend to apply the lessons learned in these 5

years to the practice in a new ward whose design andfacilities should ensure a similar degree of protectiveisolation at a reduced cost.

We thank Dr. P. E. Thompson Hancock and all the membersof the medical staff who have worked in the reverse isolation

ward, Royal Marsden Hospital, during the past five years for theircooperation; Dr. M. T. Parker and the staff of the Cross InfectionLaboratory of the Central Public Health Laboratories for phage-typing and serotyping a very large number of samples; andMrs. Maureen Bird for technical assistance and Miss JosephineRiley for the collection of specimens.

Requests for reprints should be addressed to H. E. M. K.,Royal Marsden Hospital, Fulham Road, London S.W.3.

References at faoz of next column

1. James, K. W., Jameson, B., Kay, H. E. M., Lynch, J., Ngan, H. E.Lancet, 1967, i, 1045.

2. Kay, H. E. M., Byrne, J., Jameson, B., Lynch, J. Recent ResultsCancer Res. 1970, 29, 14.

3. Robertson, A. C., Lynch, J., Kay, H. E. M., Jameson, B., Guyer,R. J., Evans, I. L. Lancet, 1968, ii, 1376.

4. Cowan, S. T., Steel, K. J. Manual for the Identification of MedicalBacteria. London, 1966.

5. Parker, M. T., John, Madeleine, Emond, R. T. D., Machacek, K. A.Br. med. J. 1965, i, 1101.

6. Report of Medical Research Council Working Party on AcuteRespiratory Virus Infections. ibid. ii, 319.

7. Bradstreet, C. M. P., Taylor, C. E. D. Mon. Bull. Min. Hlth Lab.Serv. 1962, 21, 96.

8. Grist, N. R., Ross, C. A. C., Bell, E. J., Stott, E. J. DiagnosticMethods in Clinical Virology. Oxford, 1966.

9. Fox, J. P., Elviback, L. R., Spigland, I., Frothingham, T. E.,Stevens, D. A., Huger, M. Am. J. Epidem. 1966, 83, 389.

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PSEUDOCHOLINESTERASE ACTIVITY INLIVER TRANSPLANTATION

D. B. EVANSH. LEHMANN

Renal Unit and Biochemical Section,John Bonnett Clinical Laboratories,Addenbrooke’s Hospital, Cambridge

Summary Serum-pseudocholinesterase activityhas been studied in five patients with

orthotopic liver transplantation, and decreased activityhas been demonstrated in the presence of acute

rejection and cholangitis. Successful treatment ofboth complications was followed by restoration ofnormal enzyme activity. Monitoring of the serum-pseudocbolinesterase may be useful as an earlywarning in the follow-up of patients after liver trans-plantation.

Introduction

PSEUDOCHOLINESTERASE is synthesised by the liver,and in patients with hepatocellular damage its plasmaconcentration is reduced. 1 Plasma or serum pseudo-cholinesterase activity was found by Hunt and Leh-mann 2 to be a valuable measure of liver function incirrhotic patients undergoing portocaval surgery.We have measured serum-pseudocholinesterase

activity in five patients who had undergone ortho-

topic liver transplantation, and discuss here its valuein assessing and monitoring liver function.

Methods

A preoperative blood-sample for serum-pseudocholin-esterase estimation was taken from all patients due to under-go liver transplantation, and serial measurements weremade at daily or weekly intervals after the operation.The measurement is carried out in a micromanometer