794

*** This letter has been shown to Dr Gracey and Dr Burke, whosereply follows.-ED. L.

SiR,&mdash;Dr Nalin’s clouded interpretation of our report on aspirintherapy in acute childhood gastroenteritis appears to stem from ourtable. As stated, the difference between mean stool volumes inplacebo and aspirin groups was 99 ml/day and was statistically sign-ificant (p<0-05). The difference between the "untreated" and

aspirin groups was even greater (120 ml/day) and was also signifi-cant (p<0 05), although not marked by an asterisk in the table as wefelt this was evident from the results.Our findings do not support Nalin’s suggestion that the placebo

artifactually aggravated the diarrhoea; the difference in weight gains,between these two groups was a mere 4 g/day and stool volume wasactually slightly less than that of controls in the placebo group (21ml/day). Groups did not differ significantly in degree of dehydrationassessed clinically and in weight on entering the trail. Numbers inthe untreated group were less than in the other groups to avoid theload of stool collections carried out by busy nurses. This untreatedgroup was included only to check that the placebo did not exacer-bate diarrhoea. Oral maintenance and entry to the trial began withintwo hours of admission for all patients.Nalin is correct about the discrepancy between stated glucose con-

centrations ; 3 - 7% was used throughout the trial and lactose-con-taining fluids were not used during the period of observation.Our clinical assessment of the results of this double-blind trial is

supported by the statistical analysis of the results and suggest to usthat further, carefully planned studies of a potential antisecretoryeffect of aspirin in acute gastroenteritis should be undertaken.We share Nalin’s implied concern about indiscriminate and un-

controlled use of drugs, such as aspirin, with known side-effects andreiterate our conservative approach to the treatment of gastroenter-itis. In particular, gastrointestinal side-effects and aggravation ofacidosis are untoward effects with potentially harmful results ininfants and young children. We should re-emphasise that the doselevels we used were well within the recommended range for age.The recent reports of beneficial effects of other salicylates in diar-rhoeal disorders 1,2 lead us to hope that these and other antisecretorydrugs will be carefully evaluated. Meanwhile, oral rehydration isalready well established as beneficial in the management of dehyd-rating diarrhoeal diseases and pharmacological approaches shouldbe considered an adjunct to, rather than a-replacement for, oraltherapy.Princess Margaret Children’s Medical

MICHAEL GRACEYResearch Foundation, MICHAEL GRACEYPerth, Western Australia 6001 VALERIE BURKE

IRON CHELATION WITH ORAL DESFERRIOXAMINE

SIR,-The treatment of chronic iron overload in patientsreceiving regular blood transfusions is at present based on the use ofdesferrioxamine as an iron chelator. The most satisfactory regimeninvolves daily slow subcutaneous infusion of the drug. Althoughresults from a number of centres show that it is technically possibleto induce negative iron balance in most patients by this method, it isquestionable whether the techniques available are acceptable formore than a minority of patients in terms of the social and financialcost. An oral form would be a considerable advantage.The search for new, biologically active, iron chelating drugs has

revealed a large number of possibilities3 and oral administration hasbeen shown to be effective in some cases.4 However, clinical trialscannot be carried out, even with the more promising new chelatingagents, because of the absence of satisfactory toxicity studies.

1. Du Pont HL, Sullivan P, Pickering LK, Haynes G, Ackerman PB. Symptomatic treat-ment of diarrh&oelig;a with bismuth subsalicylate among students attending a Mexicanuniversity. Gastroenterology 1977; 73: 715 - 18.

2. Du Pont HL, Sullivan P, Evans DG, Pickering LK, Evans DJ, Vollet JJ, Ericsson CD,Ackerman PB, Tjoa WS. Prevention of traveler’s diarrhea (emporiatic enteritis):Prophylactic administration of subsalicylate bismuth. JAMA 1980; 243: 237-41.

3. Jacobs A Iron chelation therapy for iron loaded patients. Br H&oelig;m 1979; 43: 1-5.4 Hoy T, Humphrys J, Jacobs A, Williams A, Ponka P. Effective iron chelation following

oral administration of an isoniazid-pyridoxal-hydrazone. Br J H&oelig;m 1979; 43:443-49.

MEAN DAILY URINARY IRON EXCRETION AFTER ORAL

ADMINISTRATION OF DESFERRIOXAMINE MESYLATE OR STEARATE

FOR 2 DAY PERIODS IN DIVIDED DOSES OF 100 mg/kg DAILY

We have recently looked at the effect of orally administered des-ferrioxamine mesylate, with results similar to those found by DrCallender and Professor Weatherall (Sept. 27, p.689). In additionwe looked at the effect of the fat soluble desferrioxamine stearate

(kindly supplied by Professor Nuesch and Dr Desaulles of Ciba-Geigy Ltd.) on urinary iron excretion in normal and iron loadedsubjects, hoping that intestinal absorption might be greater than forconventional, water soluble, mesylate. The results are shown in thetable.

<

While desferrioxamine mesylate produced a significant increasein iron excretion the stearate is relatively ineffective. The amount ofiron excretion induced by oral desferrioxamine would be inadequateto produce negative iron balance in a chronically transfused patientand the dose used in these studies was quite large, but attention isdrawn once again to the possibility of effective oral iron chelationtherapy which has already been demonstrated using another agentin laboratory animals.4 This form of therapy seems to offerpotentially the most satisfactory regimen for patients with ironoverload, providing that a non-toxic, well absorbed, chelator can befound.

Department of H&aelig;matology University of Wales, ALLAN JACOBSHeath Park, Cardiff CF4 4XN WEN CHANG TING

MUSHROOM POISONING

SIR,-Your Aug. 16 editorial was timely, this being the peakseason for mushroom eating on the continent of Europe. The articleis reasonably informed, drawing upon the First International Sym-posium on Amanita Toxins and Poisoning, which I have sum-marised elsewhere. Nevertheless some of the data need to bebrought up to date.Three mushrooms (50 g fresh tissue) may be sufficient to kill not

just one but two or three people. Case histories suggest that humansare at least as susceptible to amatoxins as the most sensitive labora-tory animals, the dog and the guineapig (LD5o about 0 - 1 mg ama-toxins per kg body weight). By chromatographic and immuno-logical methods we have detected 5-8 mg of amatoxins in a singlemushroom (20-25 g), which probably represents the lethal quantityfor a man.2,3

I agree that, for Amanita poisoning, the gastrointestinalsymptoms developing after a typical time lag of 6-12 h still providean important clue to the diagnosis. However, these symptoms aremost probably not caused by phallotoxins because vomiting anddiarrhoea in dogs can be produced by pure amatoxins alone.4,5 It ismore likely that the gastrointestinal symptoms reflect early damageto cells of the epithelial lining of the intestine occurring after enteraland parenteral application of the toxins.5 The presumption thatphallotoxins are the cause of these symptoms arose from themisleading correlation between the early death of laboratory

1. Faulstich H. New aspects of amanita poisoning. Klin Wschr 1979, 57: 1143-522. Faulstich H, Georgopoulos D, Bloching M, Wieland T. Analysis of the toxins of

amanitin-containing mushrooms. Z Naturforsch 1974; 29c: 86-88.3. Bodenm&uuml;ller H, Faulstich H, Wieland T. Distribution of amatoxins in Amanita

phalloides mushrooms. In: Faulstich H, Kommerell B, Wieland T, eds. Amanitatoxins and poisoning. New York: G. Witzstrock Publishing (in press).

4. Faulstich H, Fauser U. Untersuchungen zur Frage der H&auml;modialyse bei der Knollen-bl&auml;tterpilzvergiftung. Dt Med Wschr 1973; 98: 2258-59.

5. Fiume L, Derenzini M, Marinozzi V, Petazzi F, Pestom A. Pathogenesis of gastro-intestinal symptomatology during poisoning by Amanita phalloides. Experientia1973; 92: 1560..