875

NO PROVOCATION WITHOUT FOUNDATION

SIR,-We should be grateful to Colonel Hall (April 20,p. 743) for reporting his inability to confirm the value 01the " provocative test in malaria " using adrenaline injec-tions. This test originates from casual observations madeduring the 1914-18 war 1,2 and has often been citedwithout any justification of its practicability.Sinton 3 reviewed the subject and tested the use oi

adrenaline, strychnine, and typhoid vaccine on 478 patientsin India. Of these some 350 were given subcutaneousinjections of adrenaline. Sinton’s judgment was alwaysremarkably sound and his opinion was that " none of theprovocative methods showed any advantage for the diag-nosis of an uncured latent malaria ". My own attempts tcassess the usefulness of this method on adult Nigerianpatients were consistently negative. 4The supposed therapeutic contraction of the enlarged

malarious spleen under the influence of adrenaline waswidely reported by Maurizio Ascoli 5 during the 1930sAscoli and several of his colleagues 6 developed thi!treatment of " chronic malaria " by giving their patient:small (0001 mg.), but gradually increasing, daily doses ointravenous adrenaline and claimed that this methocprevented relapses of malaria especially when quinine wa:subsequently administered. Ascoli’s treatment had : number of followers but also several critics, 8,9 wh<

pointed out the side-effects of intravenous adrenalineThis method has now been relegated to the limbo o:

medical history. It seems that the use of adrenaline fo:

" provocative tests " in diagnosing malaria infection maybe consigned to the same oblivion.London School of Hygiene and

Tropical Medicine,London WC1E 7HT. L. J. BRUCE-CHWATT.

HYPOTENSION AND BRADYCARDIA AFTERLIVER BIOPSY

SIR Dr Sullivan and Dr Watson (March 9, p. 389)drew attention to an infrequently reported complication ofliver biopsy which they called " neurogenic hepatic hypo-tension ". We wish to report the incidence of this eventin 801 consecutive patients submitted to Vim Silvermanneedle liver biopsy from January, 1973, to March, 1974,in whom the complications of this procedure were investi-gated prospectively.Hypotension, bradycardia and epigastric and shoulder-

tip pain developed between 2 and 5 minutes after thebiopsy in 5 patients (0-6%). In another patient onset ofhypotension appeared 3 hours after the biopsy and it lasted4 hours; signs of hypovol&aelig;mia (tachycardia and fall inhaematocrit) were not observed.A vasovagal stimulation due to the penetration of the

pleura by the needle, the peritoneum, or/and the liver canexplain this phenomenon, but no adequate explanation isapparent for the latest case in which hypotension did n01immediately follow the biopsy.The importance of recognising this event seems to be

in differentiating it from hypotension due to intraperitonea:haemorrhage, particularly when recovery is slow or thertis a long interval between needle biopsy and hypotension.

Prognosis has been usually as good, as in cases reported1. Abl, R. Munch. med. Wschr. 1919, 66, 180.2. Sassen, P. Arch. Schiffs. Tropenhyg. 1919, 23, 235.3. Sinton, J. A. Ind. J. med. Res. 1925, 13, 603.4. Bruce-Chwatt, L. J. West Afr. med. J. 1963, 12, 141, 199.5. Ascoli, M. Rif. med. 1936, 52, 351.6. Ascoli, M. Nuove vedute sulla malaria. Rome, 1946.7. Livierato, S. Acta Conventus Tertii de Malariae Morbis; vol. II,

p. 476. Amsterdam, 1938.8. Casini, G. Riv. Malar. 1939, 18, 189.9. Marotta, G. ibid. p. 194.

by Dr Sullivan and Dr Watson, and recovery was rapid inall but 1 case.

A 55-year-old woman with alcoholic liver disease developedsevere hypotension and abdominal pain some minutes after liver

. biopsy. After intravenous perfusion of plasma expanders theblood-pressure reached 70/40 mm. Hg after two hours. In spiteof the absence of tachycardia a presumptive diagnosis of haemo-peritoneum was made and she was submitted to laparotomy.During the anxsthesia the patient had an episode of cardiacarrest from which she recovered after external cardiac massage.The laparotomy showed no blood in the abdominal cavity. Shedied of a second cardiac arrest during the operation. This caseis very similar to the cases of neurogenic shock reported byKlatskin and Rumball.

Liver Unit,Hospital Clinico y Provincial,Universidad de Barcelona,

Spain.

J. M. BORDASC. BRUM. BRUGUERA.

CHENODEOXYCHOLIC ACID AND THE LIVER

SIR,&mdash;In view of recent reports that chenodeoxycholicacid (C.D.C.A.) may be toxic to the liver in adult and fetal 2rhesus monkeys, Dr Bainton and colleagues (March 30,p. 562) are right to be cautious about the use of this bileacid in the treatment of patients with gallstones. However,in a preliminary communication 3 and in a paper shortly tobe published,4 we have presented evidence that, in doses ofup to 1.5 g. daily, C.D.C.A. does not seem to be hepatotoxicin man. Although initially we did find a slight, butstatistically significant, rise in serum isocitric-dehydro-genase levels after treatment with C.D.C.A.,5 subsequentlywe showed that with larger numbers of patients thisdifference was no longer significant.4 Like Bainton et al.,we found no change in serum protein, bilirubin, alkalinephosphatase, and glutamic-oxaloacetic-transaminase levelsduring treatment. Furthermore, in our patients, serum-y-glutamyl-transpeptidase levels, the kinetics of clearance ofa single bolus injection ofB.s.p., and the apparent maximumexcretory capacity (Tm) of infused B.S.P. were unchangedduring treatment. Finally, we found no difference in

fasting serum-bile-acid-levels nor in liver histology be-tween patients with gallstones who had been treated withC.D.C.A. and those who had received no bile-acid therapy.Dr Bainton’s patients were given a standard dose of 1 g.

C.D.C.A. a day. The hepatotoxic effects of C.D.C.A. in

laboratory animals were dose-related and, if the samesituation prevails in man, it would seem logical to use thesmallest dose of C.D.C.A. which will still improve cholesterolsolubility in bile and ultimately dissolve gallstones. Wehave recently shown that both the incidence of abnormalliver-function tests and the reduction in the saturation ofbile with cholesterol are dose-related but that C.D.C.A. in adose of 500-750 mg. daily is both effective and safe. gAt first sight, the failure of C.D.C.A. in the Cardiff study

to change gallstone size seems to conflict with other pub-lished results. However, this lack of therapeutic effect maywell be due to the " high proportion of calcified or largestones ". Experimental studies in our laboratory haveshown that the most rapid gallstone dissolution occurredwith small, radiolucent stones which were rich in cholesterol,while the presence of a calcified ring markedly slowed therate of dissolution.’ 7

1. Lee, M. R. Personal communication.2. Heywood, R., Palmer, A. K., Foll, C. V., Lee, M. R. Lancet, 1973,

ii, 1021.3. Bell, G. D., Whitney, B., Lewis, B., Thwe, M., Dowling, R. H.

Q. Jl Med. 1973, 42, 824 (abstr.).4. Bell, G. D., Mok, Y. Y. I., Thwe, M., Murphy, G. M., Henry, K.,

Dowling, R. H. Gut (in the press).5. Bell, G. D., Whitney, B., Dowling, R. H. Lancet, 1972, ii, 1213.6. Mok. M. Y. I., Bell, G. D., Dowling, R. H. Gut (in the press)

(abstr.).7. Whitney, B., Dowling, R. H. Gut, 1972, 13, 836 (abstr.).