714

We suggest that the association between P.B.c. and coeliac disease reported by Dr Logan and his colleagues may also encompass C.A.H. with features of P.B.c. plus dermatitis herpetiformis. Unless these associations are shown to be due to chance a search for malabsorption will be indicated in all patients with P.B.c. and C.A.H. who show steatorrhoea and/or moderate anaemia. ANTONIO CRAXÌ 3rd Institute of Medical Pathology,

GIOVAMBATTISTA PINZELLO LORENZO OLIVA LUIGI PAGLIARO

University of Palermo, Division of Internal Medicine, 180 Palermo, Italy

PULMONARY ŒDEMA AFTER CONTRAST MEDIA

SiR,—The aetiology of the pulmonary oedema reported by (Feb. 25, p. 413) in 5 of 68 patients undergoing retrograde femoral arteriography is, as Malins states, probably multifactorial, but a potent factor was the use of inappropriate contrast media. 3 of the patients were given ’Conray 325’ and the other 2 ’Conray 420’: neither formulation is recommended for peripheral arteriography, and this is clearly stated in the Dr Malins

company’s literature. Both conray 325 and conray 420 are injections of sodium iothalamate and their osmolality is considerably higher than that of ’Conray 280’ injection containing meglumine iothalamate. It is this, added to the apparently excessive dosage of 200 ml in the case of conray 420, rather than any antecedent history of myocardial disease, which was probably the major cause of the pulmonary oedema. I agree with Malins’ comments on the need for preoperative cardiological assessment, attention to fluid balance, and monitoring of the volume of infusion fluid in patients undergoing any form of arteriography. Medical Information Department, May & Baker Ltd, Dagenham, Essex RM10 7XS



z This letter has been shown

J. GOULTON

to

Dr

Malins, whose reply fol-

lows.-ED.L.

ALCOHOLICS ANONYMOUS

SIR,-Dr Henry and Dr Robinson’s survey of Alcoholics Anonymous (Feb. 18, p. 372) provides useful insight into how that organisation operates. However, we need much more information before we can properly assess its therapeutic value for individual clients. In assuming efficacy without providing evidence Henry and Robinson would seem to be perpetuating an uncritical attitude to A.A., an attitude which bedevils alcoholism treatment as a whole. Only a tiny minority of British alcoholics seem to find A.A. helpful.’·2 Thus in 1970 there was a total U.K. active group membership of 7740 out of a probable alcoholic population of half a million.3 Henry and Robinson (despite their hope that their paper will help doctors make better-informed referrals) tell us virtually nothing of the patient characteristics likely to predict benefit from A.A. attendance. For instance, are high social class or i.Q., single status, or religious proclivity relevant to outcome? There is no convincing scientific evidence that adherence to A.A. in general4 or any particular component of the.A.A. programme (e.g., the "twelve steps")s improves on natural remission-rates. Not only have most studies used inadequate improvement criteria (e.g., abstinence alone) but also methodological difficulties (e.g., self-selection of the better motivated and low follow-up penetration) have rendered interpretation of results equivocal, to say the least. Where methodology has been satisfactory, 6, no advantage has accrued to A.A. membership. A.A. seem very reluctant to allow scientific study of their approach or to keep adequate records. There are even data suggesting that A.A. attendance can be harmful. In one study9 7% of relapsers blamed A.A. for their most recent relapse. And, at least in the U.S.A., the organisation seems antipathetic to alcohol clinic attendance. In short, A.A. is sorely in need of prospective, controlled studies of its value and efficacy. Northgate Hospital, Morpeth, Northumberland NE61 3BP

SiR,—The valuable survey by Dr Henry and Dr Robinson doctors "to make better-informed judgrecommend A.A. to particular alcoholic patients". Having found close collaboration with A.A. very valuable over a period of over 25 years"," I feel that doctors could make it easier for patients to accept A.A. if they were to . discuss with their patients the problems and misconceptions should

ments

SiR,—Iagree with Dr Davies (March 11, p. 556) that pulmonary oedema is a toxic effect of contrast media and should not be confused with an adverse reaction of unknown aetiology. The outstanding features in the five patients with pulmonary oedema were not only a history of myocardial disease and the use of hypertonic contrast media but also the inappropriate use of large volumes of arterial flush solution which was neither monitored nor closely controlled by the radiologist. On the question of dosage, the manufacturers said that there was "no apparent maximum safe dose" of contrast media. If 1 ml/kg is widely accepted, should it not be included on the manufacturers’ literature? Their information to users of ’Conray’ (280, 325 and 420) specifically precludes the use of conray 325 and 420 for direct femoral arteriography, but not for radiological visualisation of the distal descending aorta and peripheral vascular tree, the procedure done in all sixty-eight patients in the series in which the five complications were noted. Patients investigated by translumbar aortography were excluded from the series. The relationship between the adverse effects on the cardiovascular system and the use of hypertonic contrast media should act as a spur to the perfection of non-invasive techniques for investigation of patients with peripheral vascular disease. Department of Anæsthetics, Queen Elizabeth Hospital, Birmingham B15 2TH

A. F. MALINS

H. G. KINNELL

certainly help

...

newcomers

whether

to

may encounter.

A.A. groups vary greatly, and newcomers should attend several until they find the most congenial one. Some groups favour informal, free discussion; others rely on more formal talks. Patients who object to a "confessional" approach, for example, will probably prefer the discussion groups. A newcomer should try to be sober at his first A.A. meeting, otherwise little may sink in and he may misinterpret what is said. This is important because the ambivalent alcoholic may be keen to find faults with a fellowship aimed at helping him to stop drinking. If he finds many things wrong at his first 1. McCance, C., McCance, P. F. Br. J. Psychiat. 1969, 115, 189. 2. Timsovic, M. Hosp. Commun. Psychiat. 1970, 21, 94. 3. Kissin, B., Begleiter, H. The Biology of Alcoholism; vol. v, p.

445. New

York,1977. 4. Bebbington, P. E. Br. J. Psychiat. 1976, 128, 579. 5. Kissin, B., Begleiter, H. The Biology of Alcoholism; vol. v,

p. 465.

New

York,1977. 6. Williams, T. K. Doctoral dissertation. Western Michigan University, 1970. 7. Oakley, S., Holden, P. H. Inventory, N.C. 1971, 20, 2. 8. Strayer, R. Q. Jl Stud. Alcohol, 1961, 22, 9. Ludwig, A. M. ibid. 1972, 33, 91. 10. Glatt, M. M. Lancet, 1955, i, 1318. 11. Glatt, M. M. Br. J. Addict. 1955, 52, 55.

471.

715

meeting

he may feel able

to

avoid further attendances and

to

continue drinking with a less bad conscience. A.A. is open to anyone-this is its strength, but it creates too. The newcomer may meet all kinds of people. A few may even have had some drinks (but that does not mean that all A.A.s are hypocrites). Psychopaths may be found in A.A. as anywhere else, but they are a small minority; the newcomer, exercising caution at first, will soon be able to form valuable friendships. Nor should alcoholics be put off by the "spiritual" approach: A.A has important spiritual aspects, but agnostics and atheists have found invaluable help too. Most A.A. members are "loss of control" (gamma) alcoholics,12.13 but other types of alcoholic can also benefit from A.A. provided they understand and make allowances for the differences. Similarly the alcoholic referred by an alcoholism unit must understand the difference between the group psychotherapy approach of the unit and the repressive-inspirational approach of A.A." Most A.A. members are, quite rightly, critical of drugs. The general practitioner should warn his patient, to whom- he has prescribed disulfiram, against giving up these tablets as soon as he hears at a meeting that he does not need them. Many alcoholics may have recovered with A.A. alone; some may need other approaches as well, and A.A. and alcohol-deterrent tablets can often be complementary. There is no "official" A.A. view on disulfiram; and A.A. realises full well that alcoholics often require medical assistance as well. As your contributors say, sponsorship is a cornerstone of A.A. and helpful to the sponsor as well as to.the newcomer. In general newcomers with only a few months of sobriety should not risk trying to befriend an unmotivated alcoholic who is still drinking. "Twelve-stepping" a still-drinking member of the opposite sex is probably best avoided. Despite these pitfalls the doctor prepared to learn about A.A. will find this fellowship-and the sister organisation AlAnon for the long-suffering spouses of alcoholics-a great ally.

problems

U.C.H. Alcoholism Teaching Outpatient Centre, St. Pancras Hospital, London NW1

M. M. GLATT

PROGRESSIVE VISUAL LOSS AFTER EIGHT YEARS ON CLIOQUINOL a

SiR,-We have lately examined a 53-year-old lecturer with 2-year history of progressive visual loss. He had been in

excellent health until the onset of this illness and denied any other symptoms, The family history was non-contributory. When we asked about past medical illnesses he told us of an 18-year history of "colitis" for which he had been treating himself with clioquinol (’Entero-Vioform’) for the previous 10 years. He took three tablets daily (750 mg clioquinol) but occasionally he increased the dose up to eight tablets for a day or two if he had a loose bowel movement. Ophthalmological examination showed a slightly pale disc in both eyes. The fundi, including the maculse, were otherwise normal. Skull X-ray, perimetry, and intraocular pressure were normal. No other abnormality was noted on neurological examination. His visual acuity was 20/400 in both eyes. He was told to stop taking clioquinol immediately. His visual acuity changed to 20/200 1 week after he had stopped taking the drug. Acuity stabilised at 20/50 7 months later, and he can now read newspapers and drive, two things he had not been able to do in the 6 months before abandoning self-medication. Optic atrophy and subacute myelo-optic neuropathy atter prolonged use of hydroxyquinoline derivatives are well known, but the onset of visual loss in this patient began 8 years after the start of self-medication. The longest interval in previously reported cases known to us is 2 years.! After the rapid and dra12. Jellinek, E. M. The Disease Concept of Alcoholism. New Haven, 1960. 13. Glatt, M. M. Alcoholism: a Social Disease. London, 1975. 1. Etheridge, J. E., Stewart, G. T. Lancet, 1966, i, 261.

matic recovery of visual function in this

case we now specifically ask about the use of anti-diarrhoea medications whenever a patient presents with progressive visual disturbance. This should be done in any country where halogenated, hydroxyquinoline derivatives are still being sold "over the counter".

of Neurology and Dariush-Kabir Medical School, Tehran University,

Departments

Ophthalmology,

Tehran, Iran

IRAJ DERAKHSHAN MAJID FOROUGH

LOW-DOSE ORAL PROPRANOLOL

SIR,-Dr Davies and his colleagues claim (Feb. 25, p. 407) that the demonstration of p-adrenoceptor blockade with lowdose- propranolol is not consistent with the existence of a threshold for the hepatic first-pass effect in man. However, their data do not allow this conclusion to be drawn. A first-pass effect was first described by Gibaldi et al.l who analysed the concentration-time curves for orally and intravenously administered propranolol reported by Shand et al .2 A first-pass effect was subsequently confirmed in several species, including rat/,4 dog,s.6 and man.’ All these studies have shown that at low blood concentrations, such as those seen after intravenous administration, propranolol is extracted across the liver. The hepatic extraction of propranolol is concentrationdependent,’ and when the drug is administered orally the ability of the liver to extract and metabolise it is diminished once a "threshold" concentration or dose has been exceeded. However, no-one has claimed that extraction is complete at any dose level: Shand and Rangno found that after oral doses of less than 30 mg trace amounts (at around the limits of detection by fluorimetric assay, which most believe to be 8 ng/ml) were detectable in the systemic circulation. The more sensitive gas-chromatographic method has allowed Davies et al. to measure lower concentrations with confidence, but their findings in no way negate the threshold concept since they did not attempt to estimate the area under the concentration-time curve. Furthermore, their finding that low-dose propranolol produces significant p-adrenoceptor blockade is not new. Indeed, Paterson et al.8 showed in 1970 that a single 40 mg oral dose could produce effects lasting up to 24 h, and Leonetti and colleagues9 have confirmed that a similar dose has highly significant effects on plasma-renin-activity. Plasma-renin suppression is apparently a sensitive index of p-adrenoceptor blockade, as is singledose isoprenaline. However, single-dose isoprenaline has severe limitations1O and does not contribute findings which are of clinical significance. In summary, the first-pass effect has been amply proved for propranolol and has important clinical implications. To have significant therapeutic effects in angina and cardiac arrhythmias propranolol must be given in doses sufficient not only to exceed the threshold for the first-pass effect but also to antagonise the effects of catecholamines at the padrenoceptor site. Whilst the ideal therapeutic concentration is debatable it is clear that to obtain the best effects the dosage must be carefully and individually adjusted." Faculty of Medicine, University of Southampton, Medical and Biological Sciences Building, Southampton SO9 3TU

C. F. GEORGE

1. Gibaldi, M., Boyes, R. N., Feldman, S. J. pharm. Sci. 1971, 60, 1338. 2. Shand, D. G., Nuckolls, E. M., Oates, J. A. Clin. Pharmac. Ther. 1970, 11, 112. 3. Shand, b. G., Rangno, R. E., Evans, G. H. Pharmacology, 1972, 8, 244 4. Shand, D. G. and others Drug Metab. Dispos. 1973, 1, 679. 5. Shand, D. G., Evans, G. H. and Nies, A. S. Life Sci. 1971, 14, 17. 6. George, C. F., and others J. Pharmacokin. Biopharm. 1976, 4, 17. 7. Shand, D. G., Rangno, R. E. Pharmacology, 1972, 7, 159. 8. Paterson, J. W., and others Eur. J. clin. Pharmac. 1970, 2, 127. 9. Leonetti, G., and others Clin. Sci. mol. Med. 1975, 48, 491. 10. George, C. F. Br. J. clin. Pharmac. 1975, 2, 3. 11. Prichard, B. N. C., Gillan, P. M. S. Br. Heart J. 1971, 33,473.

_

Alcoholics Anonymous.

714 We suggest that the association between P.B.c. and coeliac disease reported by Dr Logan and his colleagues may also encompass C.A.H. with feature...
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