DIET AND SERUM-LIPIDS IN MALES AFTER MYOCARDIAL INFARCTION

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apparent than real, since all tend to occur particularly in association with the presence of a Y sex chromosome. is

more

Department of Obstetrics and Gynæcology, University of Leeds. Pathology Department, Royal Hospital for Sick Children, Edinburgh.

MAXIMAL HYDROCHLORIC ACID OUTPUT AFTER HISTAMINE AND MEAT EXTRACT

J. S. SCOTT. A. D. BAIN.

GASTRIN

SiR,-Professor Dragstedt’s letter (April 10) reminds us that his experimental and clinical work on gastric physiology has greatly enriched our knowledge in this field. Few clinicians will disagree with his concept that duodenal ulcers are usually caused by hypersecretion of gastric juice of nervous origin. Less convincing, however, is his concept that most gastric ulcers are caused by hypersecretion of gastric juice of humoral or gastrin origin, resulting from stasis in the antrum region of the stomach. This view could offer an explanation for the development of those gastric ulcers which are seen in connection with chronic duodenal or pyloric ulcers or hypertrophic pyloric stenosis. In these conditions food may remain in prolonged contact with the antrum which, according to Dragstedt, leads to an increased production of gastrin and subsequent parietalcell stimulation.

The accompanying table shows the maximal hour output of hydrochloric acid after both histamine (intravenous technique 3) and meat extract (peak half-hour x 2) in patients (male and female together) with duodenal, gastric, and combined ulcers. Of the simple gastric-ulcer patients 4 were females. This sex predominance alone is not sufficient to account for the extremely low response to both direct parietal-cell stimulation (histamine) and direct antral stimulation (meat extract) in this group. R. B. WELBOURN Department of Surgery, Postgraduate Medical School, G. P. BURNS. London, W.12. DIET AND SERUM-LIPIDS IN MALES AFTER MYOCARDIAL INFARCTION

I agree with Mr.

Capper and his colleagues (April 24) that this view does not explain the pathogenesis of the much more These ulcers occur precommon classical gastric ulcer. dominantly in late middle age and in the elderly. The majority of these patients have normal or hyposecretion of gastric juice, and show no evidence of any organic or functional lesion in the pyloric antrum or the duodenum. When neither hyperacidity of the gastric juice nor stasis in the antrum of the stomach seem to play a part in the development of these ulcers, could they be due to an increased vulnerability of the gastric mucosa caused by an impaired blood-supply ? I have given further evidence1 for the concept that atherosclerosis in the central blood-supply of the stomach plays an important part in the pathogenesis of gastric ulcers in patients over 50 years of age. The main argument against this has been the observation that, when partial gastrectomy is performed for peptic ulcer, the gastric and duodenal blood-vessels of the resected specimens often fail to show evidence of local arteriosclerosis. This argument can no longer be upheld. In recent years it has been shown that cerebral arterial insufficiency and obstruction is often caused by atheromatous plaques in the extracerebral blood-supply. Similarly, in renal artery stenosis, atheromatous plaques are frequently found at the origin of the renal artery while the distal portions of the stenosed artery often remain unaffected. Moreover, in most cases of mesenteric artery insufficiency or obstruction, the atheromatous plaques have been seen in the abdominal aorta and at the origin of the mesenteric artery. The evidence for the atherosclerotic xtiology of gastric ulcer is just as striking as in the above-mentioned conditions. Radiography of the abdominal aorta in 293 patients with chronic gastric ulcer between the ages of 50 and 80 revealed that the incidence of calcified atherosclerosis in the upper abdominal aorta and in the coeliac axis is significantly higher than in control cases of the same age-groups. Prince of Wales’s Wales’s General Hospital, A. ELKELES A ELKELES. N.15. London, N.15...

SIR,-We have read with interest the letters of ProDragstedt and Mr. Capper and his colleagues concerning the humoral secretion of gastric juice in gastric

fessor

ulcer. Hypersecretion of humoral origin should be detectable when the antrum is stimulated directly by meat extract as in the method previously described by us.22 1. 2.

Elkeles, A. Amer. J. Roentgenol. 1964, 91, 744. Welbourne, R. B., Burns, G. P. Proceedings of Seventh International Congress of Gastroenterology, 1964; vol. I, p. 163.

SiR,ņThe results of Dr. Little and his colleagues (May 1) oppose, as far as Canadians are concerned, those of Yudkin and Roddy that Englishmen with coronary heart-disease (c.-.D.) consume more sugar than do controls, but there is no need for anyone who believes that refined carbohydrates, especially sugar, are the cause of C.H.D. to be swayed by either of these two conflicting results. For both results ignore the vital consideration of personal constitutional make-up or " personal build ", since this, which is entirely distinct from hereditary defect, is crucial to the whole question. Consider hallux valgus. Though a hundred pairs of feet can go into shoes that are too pointed, only ten of them may develop the hallux valgus deformity-these feet are not built wrongly, and unconfined by shoes they might be particularly efficient in certain natural circumstances. But the build of these feet happens also to make them unusually vulnerable to the new environmental factor of pointed shoes-so new a factor that even today only a small fraction of humanity goes about in shoes at all. And it is this new factor in the environment, to which no adaptation can yet exist, and to which the build of these feet renders them especially vulnerable, that is clearly the basic cause of hallux valgus. In this argument it will particularly be noted that there is no need for the feet that get hallux valgus from narrow shoes to have been confined in narrower shoes than have those of most people of the same sex. The above argument, including the forms of personal build involved, is fully developed in my works linking varicose veins5 and peptic ulcerwith the new environmental factor represented by the consumption of refined carbohydrates. In a joint work with G. D. Campbell, to be published shortly, we show that what matters in practice, in the association of sugar-consumption and C.H.D., is the height of sugar-consumption in whole populations. In peoples who escape C.H.D. altogether, such as the tribal Africans, the consumption of refined sugar and flour is practically nil. In those peoples, however, who show a high incidence of the disease, such as the English, Canadian, and other Westernised nations, the consumption of sugar is usually over 100 lb. per head per annum, and the consumption of white flour is universal. 3.

Lawrie, J. H., Smith, G.

M.

R., Forrest,

A. P. M.

Lancet, 1964, ii,

270. 4. 5. 6.

Yudkin, J., Roddy, J. ibid. p. 6. Cleave, T. L. On the Causation of Varicose Veins. Bristol, 1960. Cleave, T. L. Peptic Ulcer. Bristol, 1962.

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The results of these racial studies

are

in the closest

harmony with the work on c.H.D. of Antar and his colleagues,’ who have shown that there has been only a slight increase in fat-consumption in the United States over the past 70 years (and that mainly of unsaturated fatty acids), but that there has been a progressive decline in the consumption of unrefined cereals and a dramatic increase in the consumption of sugar. But that individual persons in Westernised populations who get C.H.D. should have consumed more sugar than the very high average figure is an unnecessary stipulation. T. L. CLEAVE. LUMBAR SPINE DISORDERS AND LIFTING SIR,-With reference to Dr. Troup’s article (April 17) on the relation of lumbar spine disorders to heavy manual work and lifting, it must be emphasised that to assume that figures from the Ministry of Pensions and National Insurance are statistically unbiased will lead, if uncorrected, to fallacious reasoning. In the heavy industries which provide most of the claims to benefit under the National Insurance (Industrial Injuries) Acts, the workers are more sophisticated and more educated by their representatives, and are fully aware of the financial advantages which result when musculoskeletal disorders can be related to injuries. It should be recorded that many socalled back injuries are no more than allegations of injuryunwitnessed and unsubstantiated other than by the claimant. " Despite discrepancies and late reporting, these " accidents are difficult to refute since the Law Commissioners have ruled that an account of an accident, provided it is not unreasonable, should be accepted, even if it cannot be established.

The scientific observer should be aware of this bias in statistical analysis introduced by the motive of personal gain-otherwise our scientific literature and future textbooks are going to contain many misleading and erroneous facts concerning the relation of certain disorders to trauma. MINISTRY MEDICAL OFFICER.

A SITE OF ACTION FOR INSULIN

SIR,-We have shown that trypsin and chymotrypsin act

like insulin in

rat

diaphragm8

and lower the blood-

sugar of diabetic rats. A unique serine residue, and histidine residues, are necessary for catalytic activity in these enzymes. When these residues are chemically blocked the enzymes no longer behave like insulin. From structural similarities between the two enzymes and insulin-comprising the proximity of serine and histidine, and the position of histidine relative to a disulphide bond-we predicted that insulin might have proteolytic activity. We found9 that insulin was able to catalyse the hydrolysis of hxmoglobin, myoglobin, and an unidentified component of skeletal muscle under conditions where contamination by pancreatic enzymes was excluded. In a search for a synthetic molecule which might be a substrate, we have found that the simple dipeptide, L-leucyl-L-tryptophan, thus far manifests a unique susceptibility to attack by insulin. Both products of its insulincatalysed hydrolysis, L-leucine and L-tryptophan, have been shown to be effective hypoglycaemic agents under certain conditions.

The question whether the enzymatic properties of insulin have a physiological meaning remains unanswered. A hydrolytic or a denaturase " property might enable the hormone to lower the cell-membrane barriers to certain substrates as well as to promote integration within the cell, thereby allowing a multiplicity of reaction "

7. Antar, M. A., Ohlson, M. A., Hodges, R. E. Am. J. clin. Nutr. 1964, 14, 169. 8. Rieser, P., Rieser, C. H. Proc. Soc. exp. Biol., N.Y. 1964, 116, 669. 9. Rieser, P., Rieser, C. H. Biochem. Biophys. Res. Commun. 1964, 17, 373.

possibilities involving messenger ribonucleic acid enzymes, cofactors, and substrates to be accelerated. Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, Kentucky.

PETER RIESER.

PHYTOHÆMAGGLUTININ IN TREATMENT OF APLASTIC ANÆMIA

SIR,-Humble1 treated with intravenous injections of phytohasmagglutinin (P.H.A.) 6 cases of symptomatic myeloid aplasia, secondary to myelotoxic therapy. He reported that two patients recovered a normal peripheralblood picture, and that evidence of stimulation of bonemarrow function was found in all patients. Administration of P.H.A. was concomitant with the suspension of myelotoxic treatment and/or with the administration of other therapeutic agents, including blood-transfusion. We have treated with P.H.A. a case of primary aplastic anxmia, but by a procedure quite different from that followed by Humble. We took peripheral-blood leucocytes from the patient, and cultivated them in vitro in a medium containing P.H.A. (Preliminary studies had shown that the peripheral-blood lymphocytes of our patient develop into highly proliferating stem cells, when cultivated in the presence of P.H.A., as do the peripheral-blood lymphocytes from normal subjects.) After 48 hours of tissue culture we injected the P.H.A.-stimulated lymphocytes into the bone-marrow cavities of the patient. We decided to follow this procedure: (a) in order to avert the need for the administration in vivo of large doses of P.H.A. (which is erythroagglutinating); and (b) in order to avoid the effect of factors inhibiting the stem-cell evolution of lymphocytes, possibly present in primary aplastic anxmia. The aim of this investigation was: (1) to test the reaction in man to the periodic intramedullary inoculations of autologous lymphocytes, previously stimulated by P.H.A. in tissue culture; (2) to investigate the possible repopulation of the bone-marrow of primary aplastic anxmia by this treatment. Our patient was a woman of 32 years, in whom primary aplastic anxmia had been diagnosed twelve years previously; the diagnosis had been confirmed by repeated sternal punctures and marrow biopsy of the iliac crest. In a period of three months we made 18 inoculations of autologous stimulated lymphocytes, at intervals of two to seven days. Cells from 40 x 10’’ to 80 x 10 6 were injected each time, totalling eventually 109 injected cells. The treatment was well tolerated. In fact, except for an occasional brief temperature rise (one to four hours), we did not observe any appreciable side-effect. Moreover, the patient improved clinically. In particular, epistaxis and manifestations of purpura, spontaneous or secondary to trivial injuries, ceased. Several bone-marrow specimens (mostly from the ilium) showed good cellularity, and two of them showed even megakaryocytes; never observed before; and the peripheralblood counts improved somewhat, although the values remained definitely below the normal level. Thus, the leucocyte-count varied only slightly (between 3000 and 4800 per c.mm.), whereas the haemoglobin level and the haematocrit value increased distinctly (from 6-5 g. per 100 ml. and 23%, to 10.2 g. per 100 ml. and 30%, respectively). The platelets, like the leucocytes,.showed only slight variation in number during treatment, but in two weeks they increased in number slightly (from 28,000 to 46,000 per c.mm.). This change coincided with the finding of megakaryocytes in the bone-marrow. No significant changes were observed in the differential whiteblood-cell count during treatment. we

We intend to follow the further course of the patient, in order to ascertain whether the observed partial improvement is only transient or more lasting. Moreover, we plan to undertake further intramedullary inoculations of autologous P.H.A.-stimulated lymphocytes. In particular, 1.

Humble, J. G. Lancet, 1964, i, 1345.