TOBACCO SMOKE AND GASTRIC SECRETION

1040 The third patient had taken 2500 g. of L.s.D. Believing the tablets to be out-of-date, he had swallowed the whole amount. The day after, I saw him in a very depressed state which was relieved with chlorpromazine. Two months later, he reported morbid and continuous ruminations over abstruse questions such as the meaning of life, religion, and the universe. He was anxious and depressed, but chlorpromazine and diazepam were of little help. Addition of propranolol 10 mg. three times daily rapidly relieved his symptoms, both objectively in reducing his tachycardia and signs of anxiety, and subjectively in bringing the compulsive thinking under control. Whatever the underlying psychodynamic or pharmacological mechanisms of these anxiety states following the use of L.S.D., the value of propranolol clinically has been so striking that further clinical and pharmacological investigation would be seen to be indicated. University College London Student Health Association, 17 Gordon Street, London WC1H OAH.

ARNOLD LINKEN.

idea is not new, since I described the relief of acute left ventricular failure by intravenous tolazoline as long ago as 1952.1 At that time, I suggested that the results obtained by the method warranted further trials, and it is gratifying that my original observation has now been confirmed, albeit nineteen years later. DAVID WHEATLEY.

KININ RELEASE IN THE CARCINOID SYNDROME

SIR,-The communication of Dr. Mashford and Dr. Roberts (Oct. 9, p. 817) contains an implied criticism of the earlier conclusions of Oates et al .,2 who found raised kallikrein and kinin levels in carcinoid hepatic venous blood. Dr. Mashford and his colleague claim that, because of the rapid destruction of kinin in the lung, it is more relevant to the flushing mechanism to measure kinin levels in peripheral arterial blood. For a similar reason, Mashford and Zacest3 expressed surprise at the finding by Zeitlin and Smith4 of raised kinin levels in peripheral venous blood during the carcinoid syndrome. Oates et al. have shown that it is not merely free kinin which is released from the carcinoid tumour, but active kallikrein. While the life of free kinin in the circulation is a matter of seconds,5 kallikrein has a half-life measured in minutes5 and must recirculate several times. The active kallikrein reacts with plasma-kininogen to release free kinin, which is rapidly removed from the blood. Thus, at any moment in time and at any point in the circulation, a dynamic equilibrium exists, and the measurable free-kinin level must depend mainly on the rate of formation of kinin and the rate of its destruction at that site. At the sites where the rate of formation is even more rapid than the rate of removal, significant levels of free kinin will occur. The rapid destruction of kinin in the lung presumably ensures low levels of free kinin within the lung and in the

3. 4. 5.

I. J. ZEITLIN.

MYDRIATIC DRUGS FOR ROUTINE FUNDAL INSPECTION

SIR,-Dr. Smith is to be congratulated on his interesting stimulating article (Oct. 16, p. 837). Rapid and ade-

SiR,ŇIhave just seen the paper by Dr. Majid and his colleagues in your issue of Oct. 2 (p. 719). In fact, the

1. 2.

Wolfson Laboratories, Gastrointestinal Unit, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU.

and

VASODILATOR TREATMENT OF HEART-FAILURE

General Practitioner Research Group, 325 Staines Road, Twickenham.

arterial blood leaving it. It should have little or no influence on the kinin levels in the cutaneous microcirculation. On balance it would seem that the assay of circulating kalhkrein2 or the simultaneous measurement of kinin and kininogen levels in the venous blood draining an area of vasodilatation 4 would give an indication of the state of the kinin-forming system at least as valid as the measurement of arterial free kinin alone.

Wheatley, D. Br. med. J. 1952, i, 1174. Oates, J. A., Melmon, K., Sjoerdsma, A., Gillespie, L., Mason, D. T. Lancet, 1964, i, 514. Mashford, M. L., Zacest, R. Aust. Ann. Med. 1967, 16, 326. Zeitlin, I. J., Smith, A. N. Lancet, 1966, ii, 986. Vane, J. R. Br. J. Pharmacol. 1969, 35, 209.

quate pupillary dilatation, with minimal interference with accommodation, and short duration of effect are, of course, the criteria for the ideal mydriatic. Dr. Smith presents a good case for 0-5% tropicamide to fill this role. I must take issue with him on his condemnation of 0-1% cyclopentolate and 0-5% homatropine for fundal inspection. To combat the possible danger of precipitating angle-closure glaucoma, the use of a miotic, at least in all patients over 40 years of age, should be regarded as mandatory whatever the mydriatic previously instilled. I have found that 0’25%

physostigmine in the case of antimuscarinic mydriatics, and 1 % pilocarpine following sympathomimetic mydriatics, normally counteract the pupillary dilatation adequately within 30 minutes or so. The patient is requested to remain in the waiting-room until this is observed. The patient is also asked to return if redilatation of the pupil, accompanied by pain, is noticed within the next few hours. In view of the possibility of idiosyncrasy to tropicamide, it appears to me both unnecessary and unjustifiable to remove those very useful mydriatics, 0-1% cyclopentolate and 0-5% homatropine, with miotic cover in appropriate cases, from our list of mydriatics. Department of Ophthalmic Optics, University of Wales Institute of Science and Technology, Cardiff.

P. H. O’CONNOR DAVIES.

TOBACCO SMOKE AND GASTRIC SECRETION of Dr. Wilkinson and Mr. Johnston SIR,- The report is of interest. We have also shown that 18, p. 628)" (Sept. " of doses nicotine and tobacco-smoke condensmoking sate depress gastric-juice volume, acid concentration and acid output, and peptic activity in both gastric-fistula rats and Shay rats. 6-8 Nicotine-induced gastric secretory depression is also observed 6.8 in rats treated with maximal doses of histamine, or maximal or submaximal doses of pentagastrin. On the other hand, in rats the subcutaneous or oral administration of nicotine for 2 weeks results in gastric secretory stimulation.9,10 Moreover, in these animals inhibition of gastric secretion by acute nicotine exposure is still present,l1 indicating that tolerance to the inhibitory effect of the alkaloid on gastric 6. Thompson, J. H. Am. J. dig. Dis. 1970, 15, 209. 7. Thompson, J. H., Brückner, W. Eur. J. Pharm. 1970, 9, 261. 8. Thompson, J. H., Spezia, C. A., Angulo, M. Res. Comm. chem. Path. Pharm. 1970, 1, 230. 9. Thompson, J. H., Spezia, C. A., Angulo, M. Experientia, 1970, 26, 615. 10. Thompson, J. H., Angulo, M., Spezia, C. A. Res. Comm. chem. Path. Pharm. 1970, 1, 721. 11. Shaikh, M. I., Thompson, J. H., Aures, D. Proc. West. Pharm. Soc. 1970, 13, 178.

1041 secretion does not develop. Atropine suppresses gastric secretion equally in normal and chronic nicotine-treated rats." The gastric secretory stimulation produced by chronic nicotine administration is blocked by bilateral abdominal vagotomy 12 and by bilateral destruction of the anterior hypothalamic area and the ventromedial hypothalamic nucleus. 13 The mechanisms

whereby

acute

and chronic nicotine

administration alter gastric secretion and influence peptic ulcer disease are not known, but are probably dependent upon the summation of

a

series of separate actions

on a

variety of different organs and systems. 6, 8,13-15 Department of Pharmacology, University of California School of Medicine Center for Health Sciences, Los Angeles, California 90024, U.S.A.

JEREMY H. THOMPSON.

EPIDEMIC OF PULMONARY HYPERTENSION

SIR,-In your editorial (July 31, p. 252) you state that ’Aminorex’ did not cause pulmonary hypertension in rats. In fact, Engelhardt and Hort 16 demonstrated pulmonary hypertension in rats after chronic feeding with aminorex, though Leuschner et al. 17 and Engelhardt et al. 18 were unable to produce such hypertension. In view of these results, we measured pulmonary and systemic bloodpressures in rats chronically treated with several anorectic drugs and related sympathomimetic compounds. Mean pulmonary-artery pressures were clearly increased by doses of aminorex and chlorphentermine, which retarded the gain in body-weight of growing rats. Therefore an experimental model now exists for studying the underlying mechanism. Microscopic examination of the lungs has not yet revealed the medial hypertrophy observed in postmortem examinations of patients, and in rats after application of pyrrolizidine alkaloids." In our opinion, the medial hypertrophy is not the primary cause of the pulmonary hypertension, but rather a consequence of persistent

hypertension. Department of Pharmacology University of Kiel,

HEINZ LÜLLMANN KLAUS-ULRICH SEILER.

Kiel, West Germany.

CLINICAL ROLE FOR SENIOR NURSES

SIR,-Staff shortages are indeed commonplace in the National Health Service, as Dr. Whitehead and Nurse Fannon (Oct. 2, p. 756) point out. The geriatric services within the St. Mary’s group of hospitals have lately been reorganised, and one of the " upgraded " units found itself without access to specialists in the technical problems of reablement. Although temporary, the situation became serious when the condition of several patients began to deteriorate visibly without the regular treatments by the physiotherapist, occupational therapist, and speech therapist. In desperation, an emergency meeting was held 12. Thompson, J. H., Angulo, M. Experientia, 1971, 27, 404. 13. Thompson, J. H., George, R., Angulo, M. Proc. West. Pharm. Soc. 1971, 14, 173. 14. Thompson, J. H., Aures, D. Second Research Conference, Committee for Research on Tobacco and Health, American Medical Association Education and Research Foundation, Scottsdale,

Arizona, May 5-7, 1970,

p. 3.

15. Konturek, S. J., Solomon, T. E., McCreight, W. G., Johnson, L. R., Jacobson, E. D. Gastroenterology, 1971, 60, 1098. 16. Engelhardt, R., Hort, W. Naunyn-Schmiedebergs Arch. Pharmak.

1970, 318, 266. Leuschner, F., Otto, H., Wagener, H. H. ibid. 1970, 391, 266. Engelhardt, A., Kroneberg, G., Stoepel, K., Stötzer, H. Twelfth Meeting of the European Society for the Study of Drug Toxicity, Uppsala, June, 1970. 19. Kay, J. M., Harris, P., Heath, D. Thorax, 1967, 22, 176.

17. 18.

between the medical and nursing staff. During this meeting the senior nurses unanimously agreed that, while it was not their duty to accept therapeutic roles normally not assigned to nurses, in these untenable circumstances they would volunteer to assume such roles. Just as in the experiment described by Dr. Whitehead and Nurse Fannon, the senior nurses, headed by the principal nursing officer and with the help of the unit’s social worker, were able to investigate the background of each patient more fully than in the ordinary circumstances, and this proved to be an important factor in the success of this campaign of rehabilitation. Other, more specific methods of therapeutic rehabilitation were the use of aids and gadgets normally employed by physiotherapists and occupational therapists and the organisation of writing, picture-painting, and musical sessions for patients with speech defects. This experiment is still in progress, but already many of the patients have made good functional recovery. St. Mary’s Group of Hospitals, London.

STEPHEN SZANTO.

SiR,—Icongratulate the medical and nursing staffs of St. Francis Hospital on their initiative in allowing a more clinical role for nurses (Oct. 2, p. 756). I have long believed that the shortage of medical staff in the N.H.S. could in part be met by allowing our paramedical colleagues to play a more active role. It seems to me that we are grossly underutilising the many years of solid clinical experience possessed by all senior and many junior nursing sisters. Is there not a role for such personnel as the first line of defence at the G.P. surgery ? One could see them helping to weed out much of the trivia which are, I believe, at the root of the dissatisfaction among general practitioners, thus giving the G.P. more time to practise the highly scientific medicine which we are all now taught. At Newcastle we have a " degree " course in nursing in which the nurses are university students. Such nursegraduates, presumably of a higher academic ability and trained to a higher academic level, would seem tailor-made for this role in general practice. This course could be expanded (and modified) to include our PH.D. science graduates and perhaps some State-registered nurses and also sociology graduates, all learning the rudiments and vocabulary of medicine with a view to playing a more active clinical role. Such a group at a university could form an extremely stimulating cohort, both for themselves and their medical teachers. Department of Pathology, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP.

J. M. FORD.

REGRESSION OF NEUROBLASTOMA DURING PREGNANCY have a very interesting case of neuroblastoma seen Sir of the sympathetic chain, involving the renal pedicle, in a woman aged 29. She presented with a lung abscess, and a fixed abdominal mass (18 cm. x 13 cm.) was detected. I attempted radical excision but had to leave a strip of tumour tissue in the paravertebral gutter. There were no visceral or nodal secondaries. While she was awaiting admission to the Cancer Hospital we gave her cyanocobalamin 100 g. on alternate days-but only for six weeks, since she did not report to us owing to pregnancy. After delivery we explored her abdomen, in the course of tubectomy, for

operation. limits.

second look. Complete regression of the found. She is very well 22 months after the Her urinary catecholamines are within normal

a

tumour was