816

Stool concentrations of PG-like material in acute phase of ulcerativecolitis.

Expressed as ng PGE2 equivalents/g stool.

In the acute phase, from day 1, daily treatment consisted of 20 mgprednisone, 1’ 5 g sulphasalazine, and one prednisone enema. Asexpected the quantity of PG-like material fell during the first 4 days,but it increased rapidly thereafter. On days 9 and 10 a considerableamount of bloody mucus was passed.In another acute phase the prednisone dose was increased to 40

mg and two enemas were administered daily. Instead of a decline,mucus ecretion was enhanced to about twice the enema volume. Inthe la t chronic phase 10 mg prednisone suppositories were givenwith 5 mg prednisone by mouth. Because of an allergic reactionsulphasalazine was stopped at that time. After a few days the bloodymucous secretion diminished and after 4 weeks it had almost ceased.

I think that the unwanted effects were due to the fact that sorbitolwas added to the prednisone enemas (’Predniment’; Pharmachemie,Haarlem) the constituents of which are 25 mg prednisone and 5500mg sorbitol in sodium carrageenan/distilled water.

Sorbitol is used as an osmotic diuretic in intravenous doses of 100ml of a 50% solution, and another diuretic substance (frusemide)stimulates PG production.16 It could be that sorbitol makesinflammation worse by stimulating PG production. Further work isrequired to determine the best ratios of prednisone/sorbitol-but is it really necessary to add sorbitol to enemas used inulcerative colitis?

I thank Dr 1. T. Weterman (Academic Hospital, Leiden) and Dr J. E.Vincent.

Department of Pharmacology,Erasmus University,Rotterdam, Netherlands F. J. ZIJLSTRA

CARBON MONOXIDE POISONING ANDFIRE-ASSOCIATED DEATHS

SiR,-In his letter of Aug. 1 (p. 253) responding to your July 11editorial Professor Brandon states that "there is some clinicalevidence" that oxygen by mask or, "in severe cases", hyperbaricoxygen is effective in reducing the risk of brain damage. Not only isoxygen therapy established as effective, but also hyperbaric oxygentherapy is mandatory in confirmed cases of CO exposure withevidence of CNS dysfunction. Your editorial implied that casestoday are primarily chronic. I believe it fair to say that the medicalcommunity at large is unaware that CO poisoning is a leading causeof fire-associated deaths. The morbidity after exposure may beextensive.

16. Vincent JE, Zijlstra FJ. comparison of the formation of prostaglandins in the kidneys ofrats and rabbits, determination of the effect of furosemide. In: Prostaglandinsynthetase Inhibitors. New York: Alan R. Liss. 1980: 303-13.

The only major research into the cause of fire-associated deathsseems to have been done by a team at Johns Hopkins University’sapplied physics laboratory.’ Their figures indicated that in oneyear, 70% of the 7500 fire-associated deaths in the United Stateswere not due to smoke inhalation or the heat of the fire but were

primarily the result of acute CO poisoning. They have thus offeredan explanation for the heart-breaking puzzle as to why individualswith opportunity do not escape fires. The general public is notaware of the odourless, smokeless, and invisible death which can killin minutes. In cases of acute poisoning results of conventional testssuch as Fi02, blood carboxyhaemoglobin (COHb), or breath COanalysis, may all be normal in the face of severe poisoning, becauseof emergency treatment with oxygen for smoke inhalation orincorrect methodology.2 2CO poisons tissues with the highest metabolic rates first, such as

the heart, the basal ganglia of the brain, and other nervous tissues,not just on the basis of hypoxia, but also as a direct poisoning ofcytochrome systems; CO poisons respiration and competes withoxygen for haemoglobin and for myoglobin. Hyperbaric oxygendramatically reduces the half-life of blood COHb from 5-6 h to lessthan 30 min. The higher tissue levels achieved with hyperbaric O2presumably drive CO from cytochromes, haemoglobin, and

myoglobin.Therapeutic recommendations for suspected CO poisoning (such

as any person escaping from a burning structure with clinicaldysfunction) include imediate blood sampling, 02 by ’mask,intubation of unconscious or uncooperative patients, and

hyperbaric oxygen treatment of patients with CNS dysfunction aswell as those with COHb levels higher than 25% (or 15% with ahistory of cardiac decompensation). To avoid permanentneurological sequelae, such as basal ganglia syndromes or mentalretardation, as well as subtle emotional problems which may occureven after apparent recovery, aggressive hyperbaric treatmentshould be based on a patient’s clinical status rather than laboratoryvalue.2 A better title for your editorial would be Carbon Monoxide:an Old Enemy Unrecognised.Texas Genetics Screeningand Counseling Service,

Texas Department of Mental Healthand Mental Retardation,

Denton, Texas 76201, U.S.A. RICHARD M. ROBERTS

NO MORE LOMOTIL FOR INFANTS

SiR,-In June, Social Audit published a leaflet (noted in TheLancet of June 20), drawing attention to reported limitations of theG.D. Searle product ’Lomotil’ (diphenoxylate with atropine). Theleaflet expressed particular concern about the use of lomotil inchildren for self-limiting conditions, its use in the absence of

rehydration therapy and its use under any circumstances in

children under two years old.In the U.S. the Food and Drug Administration decided in 1973 to

require that this product be contraindicated for use in infants undertwo years old. This decision was reportedly taken3 after numerouspublished reports of accidental overdose in chidren from which itappeared that severe toxic reactions were possible at doses

unacceptably close to the alleged therapeutic dose and that infantsdemonstrated a marked and unpredictable variability in response tolomotil. Cases have subsequently been reported of severe toxicreactions in infants at, or even slightly below the alleged therapeuticdose.4Despite this lomotil has been promoted, where the regulatory

authoritv has allowed, for use in infants weighing upwards of 3 kg. 5

1. Halpin B, Fisher RS, Caplin YH. Fire fatality study. In International symposium ontoxicity and physiology of combustion products (University of Utah, Salt Lake City,Utah, March 22-26, 1976).

2. Myers RAM, Lynberg SE, Cowly RA. Carbon monoxide poisoning: The injury and itstreatment. JACEP 1979; 8: 479-84.

3 Rosenstein G, Freeman M, Standard AL, Weston N. Warning: The use of Lomotil inchildren. Pediatrics 1973, 48: 132-33.

4 Bovier-Lapierre M, Frederich A, Gillet PJ, Hartemann E, Jeune M. Quatre casd’intolerance severe au ’Diarsed’ (diphenoxylate) chez des nourrissons. Pédiatrie

1973; 28: 71-815. G. D. Searle and Co. International product disclosure. Skokie, Illinois, 1980