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possession of sick certificates than when at work. Perhapsthe most far-reaching in its consequences of the new ills,though also the most difficult to evaluate, is the removalof all personal disincentive against waste in the HealthService and in " nationalised " industries.The National Health Service in Britain has abolished

many old evils and has brought many new ones in theirplace. Mortal man is equipped neither with sufficient

knowledge nor with sufficient foresight to pronouncereliable judgment on the respective statures of the oldversus the new ills. Surely the most that mortal man canpresume to do is to learn from his mistakes and try toreach a compromise between the two systems which aimsat eliminating the worst features of each ?

Brighton, Sussex. J. E. JAMESON.J. E. JAMESON.

INTRATHECAL METHOTREXATE

EDWARD S. BAUM.

Department of Pediatrics,Fitzsimons General Hospital,

Denver, Colorado.

H. FREDERICK KOCH.

Wilford Hall,U.S.A.F. Medical Center,

San Antonio, Texas.

DONALD G. CORBYDANIEL C. PLUNKET.

Department of Pediatrics,Fitzsimons General Hospital,

Denver, Colorado.

SIR,-The letters of Back, Bagshawe et al.,2 and

Pasquinucci et awl. describing serious neurological reactionsfollowing administration of intrathecal methotrexate forleukxmic meningitis prompt us to report our own experi-ence in two children.The first patient, a 6-year-old girl, acquired acute lym-

phoblastic leukaemia in November, 1968. Following induc-tion with vincristine and prednisone, remission was main-tained with a combination of oral cyclophosphamide,6-mercaptopurine, and methotrexate together with " pulses "of 1-5 mg. per sq. m. of vincristine intravenously and1000 mg. per sq. m. of prednisone orally in 3 divided doses.This pulse was given every 3 months. In an attempt to

prolong remission by preventing leukaemic meningitis,methotrexate (12 mg. per sq. m.) was instilled intrathecallyduring each pulse. She received five pulses withoutdifficulty, and the cerebrospinal fluid was normal beforeeach instillation of methotrexate. On Sept. 24, 1970, shereceived her sixth pulse. Cerebrospinal-fluid examinationat that time was normal. The next day she complained ofmalaise, fever, and a stiff neck. Physical examinationrevealed minimal meningeal signs but was otherwise withinnormal limits. Cloudy cerebrospinal fluid was obtainedwhich contained 2800 white blood-cells per c.mm., of which

95% were polymorphonuclear leucocytes. Cell morphologywas evaluated by adding freshly obtained cerebrospinal fluidto salt-poor human albumin, centrifuging, and staining thecell button with Wright-Giemsa. No malignant cells wereseen. Gram stain revealed no organisms, and cultures forbacteria, acid-fast organisms, and fungi were negative. Apresumptive diagnosis of bacterial meningitis was made, andthe child was treated with intravenous ampicillin for 7 days.Within 24 hours she was afebrile. A repeat spinal tap onOct. 2 was normal. Cultures were again negative. On Oct. 4she complained of weakness in the legs. Physical examina-tion revealed weakness in all four limbs and decreaseddeep tendon reflexes in the lower limbs with no sensorychanges. A repeat cerebrospinal-fluid examination wasentirely normal. Over the next 10 days the paresis extendedto involve all four limbs, the deltoids, and the right facialnerve. On Oct. 6, because of the possibility of leukaemicinvolvement of the spinal cord, radiation to the cervical-spinal axis was given, and she was started on prednisone40 mg. per sq. m. daily. A total of 1000 r was given overthe next 20 days. Her condition remained unchanged.Repeat spinal tap on Oct. 28 showed a moderately raisedprotein of 80 mg. per 100 ml. but was otherwise un-remarkable. She was discharged to home care on Nov. 1.At the time of writing, there has been no improvement inher paresis.1. Back, E. H. Lancet, 1969, ii, 1005.2. Bagshawe, K. D., Macrath, I. T., Golding, P. R. ibid. p. 1248.3. Pasquinucci, G., Pardini, R., Fedi, F. ibid. 1970, i, 309.

The second child, an 8-year-old boy, has been undertreatment for acute lymphoblastic leukaemia since June,1969. The treatment regimen was identical to that describedabove. On Nov. 5, the day following the fifth pulse, he wasfebrile and complained of severe headache. The followingmorning he could not walk. Physical examination revealedobvious paresis of both lower limbs and decreased deeptendon reflexes, but no sensory changes. Bladder and bowelfunction were not affected. The cerebrospinal fluid wasnormal. At present he has a spastic paralysis with increaseddeep tendon reflexes and bilateral clonus. He did notreceive radiotherapy or corticosteroids for the neurologicalcomplication.The two patients described did not have demonstrable

leukxmic involvement of the central nervous system.Assessment of the complications of other reported cases isconfused by the presence of tumour in the cerebrospinalfluid. The doses used in the reported cases have variedwidely, which suggests that total dosage may not becritical. Experience with 25 other children receivingprophylactic pulses of intrathecal methotrexate suggeststhat adverse reactions to the drug itself are not predictable.We have started a prospective and retrospective investiga-tion of time/dose relationships and excretion and retentionpatterns, as well as the possibility of more subtle neuro-logical toxicity.

E. COLI O142 AND INFANTILEENTERITIS IN SCOTLAND

SIR,-Escherichia coli 0 142.K86 was first isolated frominfants with diarrhoea in Indonesia,’ and subsequentlyfrom an outbreak of diarrhoea amongst premature infants ina Mexico City hospital. In the first outbreak most caseswere mild, but in the second one there was a high mortality(39%). In Indonesia and Mexico the flagella type was H6.From 1964 to the end of 1968, this laboratory studied

approximately 4000 strains of E. coli, mostly from cases ofinfantile enteritis in the British Isles. E. coli 0 142 wasidentified on two occasions only. On both occasions thesource was an infant with diarrhoea; one case in East

Anglia was flagella type H34 and the other in Scotlandwas flagella type H6.

Early in 1969, E. coli 0 142.K86.H6 was isolated in anoutbreak of infantile enteritis in a hospital near Glasgow,and later in the year the same serotype was isolated from 3cases of infantile enteritis in a Glasgow hospital. In May,1970, this serotype was isolated from severely ill infantsin an outbreak in a Midlands hospital. Since then the

serotype has been isolated from cases of infantile enteritis inoutbreaks in three other Scottish hospitals, one in Glasgowand the other two in a community within 50 miles of thecity.

All these hospital outbreaks were small, but in three ofthem the babies were severely ill. In several of the out-breaks at least one fatal case occurred, but these deaths wereoften complicated by other serious illnesses.

During the years 1969 and 1970 this laboratory continuedto receive E. coli from cases of infantile enteritis in mostareas of the British Isles. With the exception of the out-1. Ørskov, F., Ørskov, I., Rees, T. A., Sahab, K. Acta path. microbiol.

scand. 1960, 48, 48.2. Olarte, J., Ramos-Alvarez, M. Am. J. Dis. Child. 1965, 109, 436.