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DYSPHAGIA IN ADVANCED MALIGNANT DISEASE

SIR,-We were impressed by the careful study of dysphagia inpatients with advanced malignant disease reported by Dr Sykes andcolleagues (Sept 24, p 726) but cannot allow their pessimisticopinion of palliation by endoscopic intubation to go unchallenged.Since January, 1987, we have done palliative procedures by thismethod on 30 patients with severe dysphagia from inoperableaerodigestive tract cancer. 27 patients (90%) went home, after amedian of 3 days. 3 patients died of their malignant disease inhospital 2-6 days postoperatively, but were able to swallow in theinterim. Endoscopic intubation may have complications, but in thehands of trained oesophageal surgeons, the procedure carries amuch lower immediate mortality than the 20% cited by Sykes et al.Medical treatment with hyoscine or other anticholinergicantisialogogues is not free from undesirable side-effects. Used

selectively in patients with advanced malignant disease, an

intubation service is only minimally invasive, preserves swallowing,prevents aspiration of saliva, and can make a major contribution to adifficult clinical problem.

Thoracic Surgical Unit,Harefield Hospital,Middlesex UB9 6JH

C. BLAUTH

J. GAERS. W. FOUNTAINE. R. TOWNSEND

QUALITY OF LIFE ON ANGINA THERAPY

SiR,—In their letters both Dr Domenet and Dr Wheatley (Aug 6p 333) suggest that we (July 2, p 4) failed to show a benefit fromtransdennal glyceryl trinitrate (GTN) compared with placebobecause the dose was too low (5 mg) and because other therapieswere also used. We have compared 5 mg transdermal GTN with 10mg in a large community-based study.436 men, who were attending their general practitioners for

chronic stable angina of at least 3 months’ duration and who wereuncontrolled on oral long-acting nitrates, were randomised toreceive 5 or 10 mg GTN patches in a double-blind trial after a2-week observation period on long-acting nitrate only. The long-acting nitrate was reduced and stopped over the first 3 days of the4-week double-blind period. Patients who received other anti-anginal agents (66%) were maintained at the same dose. Efficacywas measured by self-completed diary cards recording daily attacksof chest pain and GTN consumption. The quality of lifemeasurement was the sickness impact profile (SIP).The two groups were well matched at entry for age (mean 61

years), history of myocardial infarction (45 %), daily attacks of chestpain (mean 1-3), and SIP scores. 12-2% of patients on the 5 mgpatch withdrew compared with 14-8% on 10 mg; most withdrawalsoccurred in the first 2 weeks on active treatment and were

principally due to headache. The table shows the average change inchest-pain attacks, GTN consumption, and SIP scores. There wasno difference between 5 and 10 mg in efficacy but since no placebo

group was involved, "efficacy" may have been due simply toinclusion in the trial. A significant difference was observed in thepsychosocial score of the SIP in the first 2 weeks on active

treatment, favouring 5 over 10 mg. In this period the spontaneousreporting of headaches was 11 % on 5 mg patches compared with18% on 10 mg. We concluded that 10 mg patches offered no benefitover 5 mg in terms of efficacy; moreover, the higher dose wasassociated with a greater frequency of headaches and an initialadverse effect on quality of life.Domenet also suggests that our negative results may be due to

tolerance. The data sheet recommendations should be tested in arandomised controlled trial in the community. In this situation carewould have to be taken to have the nitrate-free interval at a low-risktime. This may be at night in effort-induced angina but such astrategy might be dangerous in patients who have nocturnal angina.

Royal Postgraduate Medical School,Hammersmith Hospital,London W12 0HS

A. FLETCHERC. J. BULPITT

PREMORBID NEUROPATHOLOGY INSCHIZOPHRENIA

SiR,—To buttress his neurodevelopmental perspective of

schizophrenia, Dr Weinberger (Aug 20, p 445) describes an

interesting case without any family history but with early onset ofschizophrenia after a head injury sustained in his teens. This injuryhad prompted a computed tomographic (CT) brain scan whichrevealed ventriculomegaly and cortical atrophy some 15 monthsbefore his first psychiatric admission. There are many similaritieswith our case,l where schizophrenia of early onset emerged in theteens after a head injury and in the absence of a family history.Magnetic resonance imaging in his 20s revealed striking ventriculardilatation and prominent cortical sulcal widening. Weinbergersuggests that some cases of schizophrenia are characterised not byan active process but by a long-standing, non-progressiveneuropathological condition of developmental origin which onlyproduces clear diagnostic symptoms in early adulthood. We suggesta variant of this view-namely, interaction between a static

neurodevelopment abnormality and atrophic processes of normalageing which, in the later phases of the illness, may masquerade asprogression.CT studies show that cerebral ventricular size varies little with

age until the sixth decade, after which there is a sharp increase.2,3 Inchronic schizophrenia the age-related increase in ventricular sizemay begin a decade earlier.4,5 We suggest that long-standing,developmental periventricular abnormalities in schizophreniarender these regions more vulnerable to normal age-relatedatrophy. This interaction could be misinterpreted as progression ofschizophrenia, especially in patients who are middle aged or older.There is some current interest in whether gliosis (a putative markerto distinguish an active, neurodegenerative process from a static,

CHANGE IN SIP AND DIARY-CARD SCORES OVER RUN-IN AND DOUBLE-BLIND (DB) PERIODS*

i i i I

*Mean (95% confidence interval). Changes calculated from end of previous period, + = lIllprovement (ie, lIllproved SIP scores or reduction m pain or GTN use).tp < 0 05 for between dose comparison (Wilcoxon two-sample test)

960

developmental abnormality) might be excessive in the brains ofschizophrenic patients.6.7 Were any such excess to be found, thiscould still, on our formulation of events, have a primary basis inneurodevelopmental deviance. The atrophy of normal ageing,which is subject to large individual differences, may interact withthe consequences of developmental anomaly in schizophrenia todetermine not just cerebral morphology but also the clinical pictureand the response to treatment.8

Department of Clinical Pharmacology,Royal College of Surgeons in Ireland,Dublin 2, Ireland

Cluain Mhuire Family Centre,Blackrock, Co Dublin

JOHN L. WADDINGTON

EADBHARD O’CALLAGHANCONALL LARKIN

1 O’Callaghan E, Larkin C, Redmond O, Stack J, Ennis JT, Waddington JL. "Earlyonset schizophrenia" after teenage head injury: a case report with magneticresonance imaging. Br J Psychiatry 1988; 153: 394-96.

2. Nagata K, Basugi N, Fukushima T, et al. A quantitative study of physiological cerebralatrophy with ageing: a statistical analysis of the normal range. Neuroradiology 1987;29: 327-32.

3. Stafford JL, Albert MS, Naeser MA, Sandor T, Garvey AJ. Age-related differences incomputed tomographic scan measurements. Arch Neurol 1988; 45: 409-15.

4. Owens DGC, Johnstone EC, Crow TJ, Frith CD, Jagoe JR, Kreel L. Lateralventricular size in schizophrenia. relationship to the disease process and its clinicalmanifestations Psychol Med 1985; 15: 27-41.

5. Rossi A, Stratta P, Casacchia M, D’Albenzio L, Schiazza G, De Donatis M. Age andduration of illness as predictors of ventncular brain ratio (VBR) size in chronicschizophrenic patients. Acta Psychiatr Scand 1987; 76: 256-60.

6. Roberts GW, Colter N, Lofthouse R, Bogerts B, Zech M, Crow TJ. Gliosis inschizophrenia: a survey. Biol Psychiatry 1986; 21: 1043-50.

7. Casanova MF, Stevens JR, Bigelow LB. Gliosis in schizophrenia. Biol Psychiatry1987; 22: 1172-75.

8. Waddington JL The ageing brain, neuroleptic drugs and the enigma of schizophrenia.Ir J Med Sci 1988; 157: 135-41.

LEUKAEMIA IN YOUNG CHILDREN

SiR,&mdash;The unusual pattern of leukaemia in young children inScotland, reported by Dr Gibson and colleagues (Sept 10, p 630)prompted us to examine the Leukaemia Research Fund datacollection survey’s registrations for cases in other parts of the UK.We looked at all new registrations from Jan 1,1984, to July 31,1988.

In view of possible concern about cases subsequent to theChernobyl radioactivity accident, we grouped the children, byaddress at diagnosis, into those who might have received relativelymore radioactive fallout (Cumbria, South Wales, and Yorkshirehealth regions) and less fallout (Trent and the South-West Englandhealth regions) according to the distribution described by Clark andSmith.l The survey does not cover the whole of the UK, and onlythose parts for which data collection began on Jan 1, 1984, withcontinuation to the present and covering entire counties are usedhere. The data are presented by annual age-specific rates for anyleukaemia in children diagnosed before their fifth birthday and bybirth cohort for children born in 1983-87.The annual rates (table I) show stability of case occurrence by

area. This stability makes the Scottish observation more striking.The rates for Cumbria are higher but numbers are small and theincrease is confined to children born before 1986.

Birth cohort data (table II) more accurately reflect temporaltrends, through factors influencing events during gestation andshortly after birth. The 1988 numbers have been estimated on thebasis of the first seven months of registration and the patterns inprevious years. In table II there is no evidence for higher ratesrelated to the Chernobyl accident (ie, the 1986 or 1987 cohorts).

TABLE I-CHILDHOOD LEUKAEMIA IN SELECTED PARTS OF

ENGLAND AND WALES 1984-88*I I J

*Expressed as number of cases (and rate per 100 000 person-years) for ages 0-4 combinedwith pooled sexes, by year of diagnosis.tIncomplete ascertamment; no rates given.

TABLE II-COHORT DATA* *

I I I I

*Cohorts of cases born 1983-87 and diagnosed up to July, 1988. No adjustment formigration or death. Number of cases (rate per 100 000 live births).tadjusted numbers and rates YOB =year of birth.

However, if there is an effect it will become more apparent over thenext 2 years. The unusually high predicted figure for young cases inthe 1987 birth cohort (n = 10) is based on 5 cases found earlier thisyear (none from Cumbria or Wales). These cohorts will need a lapseof time for further cases to occur before any interpretation can beplaced upon them, and it would be dangerous to predict a trend onthe basis of these preliminary data.There is, on this basis, a clear place for routine birth cohort

analysis of childhood incidence data. The Leukaemia ResearchFund Centre in Leeds is planning such an exercise.

Funded by the Leukaemia Research Fund. We thank haematologists andpaediatric oncologists in different parts of England and Wales for theircollaboration and Mr Jon Dunnington, Mr Jim Miller, and Miss LorraineHarvey.

Leukaemia Research Fund Centrefor Clinical Epidemiology,

17 Springfield Mount,Leeds LS2 9NG

RAY A. CARTWRIGHTPATRICIA A. MCKINNEYFREDA E. ALEXANDER

JAMES RICKETTS

1. Clark MJ, Smith FB. Wet and dry deposition of Chernobyl releases. Nature 1988; 332:245-49.

TREATMENT OF ESSENTIALTHROMBOCYTHAEMIA BY ALPHA 2a INTERFERON

SIR,-Dr Giles and colleagues (July 9, p 70) report experiencewith alpha interferon (IFN-0c) in essential thrombocythaemia.Twelve patients were treated with IFN-a2b (’Intron’; Kirby-Warrick) and six with IFN-02a (’Roferon’, Roche). The dose was3 x 106 units daily, rising to 5 x 106units at day 30 if the plateletcount remained above 600 x 109f1. All patients had a better than50% decrease in platelet count by day 28 and counts remainedbelow 600 x 109/1 for 2-5 months since induction therapy, with adecrease in dose of IFN-a. Results were similar in four patientspreviously treated with chemotherapy. No difference was seenbetween IFN-a2a and IFN-cz2b’Our experience differs considerably. We treated twelve patients

with essential thrombocythaemia with roferon. In the first sixpatients (two had been previously treated with chemotherapy), thedaily dose was 9 x 106 units for 2 months, followed by 6 x 106 unitsevery 2 days for 4 months. Platelet count decreased by 50% in allpatients between day 7 and 21, and were below 400 x 109/1 betweendays 7 and 50 (table). Side-effects (asthenia, lethargy, myalgia,alopecia, and weight loss) were seen at varying intensities in allpatients and led to withdrawal of two patients. Except forone patient who remained in remission (platelet count below600 x 109/1) after a year, the three other patients became resistant totherapy between days 90 and 150. Side-effects prevented doseincreases.

Six other patients (two had been previously treated withchemotherapy) received 4.5 x 106 units daily for 2 months and thenevery 2 days for 4 months (or even 3 x 106 units daily every 2 days).Decreases of 50% in platelet count were seen later than in the firstgroup, occurring between days 15 and 120, and counts below600 x 109/1 were observed in four patients between days 15 and 45.Levels below 400 x 109 were not observed. Side-effects were lessintense than in the first group but led to withdrawal of two patientsat 3 and 4 months. Platelet count remained below 600 x 109/1 in only