DIABETES AND STRESS

959 CENTRAL HEALTH SERVICES COUNCIL ANNUAL reports, like bottled beer, should not be kept over-long from the consumer. The account of the work of the Central Health Services Council in 19511seems a little flat because the council has largely restricted itself to matters referred to it by the Minister of Health, and in some cases administrative action has long ago been taken on the strength of its findings. Moreover one of its most useful inquiries, on integration of the various services,2 was published separately a few weeks ago. Early in 1951 the council’s Standing Dental Advisory Committee found no evidence of a decline in the demands It decided, too, that on the general dental services. there was no immediate hope of substantially increasing the number of dentists beyond the existing total. " The immediate object," the committee concluded, " should be to correct the present imbalance and to secure that the limited services available were used where the need was greatest." If dentists were to devote more time to the priority classes, the demand by the non-priority groups must be curtailed, without, however, deterring people from seeking conservative treatment. " This meant, in effect, reducing the demand for dentures." The committee formed the opinion that, in any case, too great a proportion of dentists’ time was being devoted to denture work, and it suspected that some of the demand was unreasonable. On the credit side the committee found, from observation of the experimental scheme for training and employing oral hygienists, that these ancillaries " could be satisfactorily trained and usefully employed in the public dental service;’’ ; and it suggests that their contribution more than justifies the small diversion of teaching resources which the training requires." "

COUGH MIXTURES

COUGH remedies are still one of the most popular forms of medication, even though the value of many of them is open to doubt. Dunlop et al.3 have found that of 17,301 prescriptions under the National Health Service, 1382 were for cough mixtures. The lungs seem to rank second only to the stomach in the need for medicinal aid, and cough mixtures are probably used as placebos more often than any other medicines except tonics. There can, for example, be few patients with a common cold who, if they seek medical advice, are not allotted Then there is the elderly brona bottle of cough-cure. chitic who regularly demands his favourite nostrum and The public like their cough is not easily denied it. medicine ; and if refused by the doctor they will go round the corner to the chemist. In Dunlop’s analysis purely expectorant mixtures were prescribed more than twice as often as purely sedative remedies ; but of the 1382 prescriptions, 806 were for remedies containing both sedative and expectorant drugs. This, says Dunlop, indicates some therapeutic confusion ; but it might also reflect an attitude of Such an attitude is unfair to therapeutic nihilism. the sedative group of drugs, such as codeine and amidone. On the other hand, it was shown some time ago4 that the commonly used expectorants, such as potassium ’

iodide, ammonium salts, ipecacuanha, and senega, are virtually useless. Evidence to the contrary has been

based either on uncontrolled clinical impressions or on animal experiments in which the drugs were given in very large doses which, if translated into clinical practice, would be emetic. A real expectorant is badly needed ; 1. Report of Central Health Services Council for the Year Ended Dec. 31, 1951. H.M. Stationery Office, 1952. Pp. 28. 1s. 3d. 2. Report on Cooperation between Hospital, Local Authority, and General Practitioner Services. H.M. Stationery Office, 1952. See Lancet, April 26, 1952, p. 860. 3. Dunlop, D. M., Henderson, T. L., Inch, R. S. Brit. med. J. Feb. 9, 1952, p. 292. 4. Alstead, S. Lancet, 1939, ii, 932 ; Ibid, 1941, i, 308. Boyd, E. M., Palmer, M. E. Acta pharmacol. toxicol. 1946, 2, 235.

and in this respect the work of Armstrong and White 5 with deoxyribonuclease is encouraging, for this enzyme strikes at the root of the matter by liquefying deoxyribonucleoprotein-the component which chiefly accounts for the viscosity of purulent sputum. Deoxyribonuclease can be obtained from ox pancreas, rice bran, or yeast. It is administered by spray inhalation, and the results in the first clinical tests were encouraging. Streptodornase, one of the enzyxnes present in concentrates from cultures of hæmolytic streptococci, has a similar action on deoxyribonucleoprotein. Such liquefaction of purulent bronchial secretions promises to be a good deal more effective in enabling a patient to clear his air-passages than adding mucus to them, which is what the present expectorant drugs are supposed to do. Banyai s asserts that inhaled carbon dioxide, in a 5% mixture with oxygen, is an effective expectorant, which not only stimulates respiration and increases bronchial peristalsis but ‘‘ liquefies mucopurulent inflammatory exudates." Banyai’s work seems to have attracted little attention, though he first described it eighteen years

ago.7

,

DIABETES AND STRESS GOOD diabetic control is usually described in terms of accurate adjustment of insulin dosage to a regular diet. This, of course, is the basic factor; but even with a carefully devised regime the severity of the diabetes may fluctuate widely, so that the condition remains grossly unbalanced. Such changing insulin requirements are commonly associated by the patients themselves with domestic upheaval, strained circumstances at work, or other worry ; and this aspect has been studied at several large diabetic clinics, and notably at the New York Hospital. To obtain a basis for comparison Hinkle and Wolf 8 first investigated non-diabetics and found that in the fasting normal person at rest there was initially little change in the blood sugar and ketone concentrations or rate of urine output ; but later in the fast day the bloodsugar fell slowly to 40-50 mg. per 100 ml. and the bloodketone concentration rose. At about the same time there was moderate diuresis. Similar changes took place in normal people in stressful situations without starvation. Hinkle and Wolf carefully avoid implying that the emotions occasioned by the stress caused these metabolic changes ; but they did notice a correlation between anxiety and diuresis, and between anger, dejection, resentment, or loneliness and a rise in bloodketones. In diabetics the metabolic response to psychological stresses was similar but often greater. Moreover "stress diuresis" associated with anxiety may be induced in diabetics whether or not they have glycosuria. 9 On the other hand, under basal conditions, up to 7% glucose can be passed in the urine without polyuria.8 The usual initial reaction of a fasting diabetic to a stress situation was a transient fall in blood-sugar, occasionally great enough to cause hypoglycaemic symptoms, and an increase in blood-ketones. If theo stress persisted the blood-sugar was likely to rise,’O especially when fear or anger were prominent features of the emotional response. Carbohydrate tolerance was also found to be affected by stress. Circumstances associated with resentment or sadness tended- to accentuate the diabetic type of glucose-tolerance curve, whereas with less stress or with anxiety the sugartolerance was not so impaired. Diabetics with initially high blood-sugar levels reacted to conflicts by a rapid rise in blood-ketones and greatly increased secretion

prescribed

5. Armstrong, J. B., White, J. C. Lancet, 1950, ii, 739. 6. Banyai, A. L. J. Amer. med. Ass. 1952, 148, 501. 7. Banyai, A. L. Amer. Rev. Tuberc. 1934, 30, 642. 8. Hinkle, L. E. jun., Wolf, S. J. Amer. med. Ass. 1952, 148, 513. 9. Hinkle, L. E. jun., Edwards, C. J., Wolf, S. J. clin. Invest. 1951, 30, 818. 10. Dunbar, F. Emotions and Bodily Changes. New York, 1946

p. 186.

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960 of water, glucose, ketones, chloride, and fixed base. In this way the metabolic changes typical of diabetic ketosis can develop rapidly 11; and in fact episodes of diabetic ketosis are often connected with stressful situations.12 Diabetes, when it first presents, commonly does so in a setting of stress, such as a reverse in business or loss of a near relative. At the time of the flying bombs such stress reactions were very evident in London diabetic clinics. A near miss from a flying bomb might score a direct hit on the diabetes, which would temporarily require greatly increased doses of insulin. Such factors should not be forgotten in the less dramatic conditions of peace ; for helpful general advice and understanding can do much to lessen the fluctuations in the disease.

INTRAVENOUS ADMINISTRATION OF FAT COMPLETE parenteral feeding is feasible ; for not only carbohydrates, proteins, and vitamins, but also emulsified fats, can be administered intravenously. Thus an unconscious or badly injured patient can be kept alive for weeks or even months without recourse to oral feeding. Stare and his colleagues 13 at Harvard kept a badly shocked patient alive for 67 days by daily intravenous infusions of fluid containing fat emulsion, glucose, and protein hydrolysates ; the fat provided 1200 calories daily and the other components 1100 calories. There are two major problems in intravenous feeding : the prevention of thrombophlebitis, and the provision of enough calories in a limited quantity of fluid, since with too large a volume the patient will be waterlogged. Carbohydrate and protein in high concentration will cause withdrawal of fluid from the tissues and irritate the vein into which the infusion is made, possibly with does ensuing chemical thrombophlebitis. This not arise with fat emulsions. Emulsified fat particles do not exert an osmotic effect and may be injected in high concentrations in a relatively small volume of fluid. Thus it is possible to provide 1600 calories a day in fat emulsions alone. Johnson et al.14 have shown that unsuitable emulsifying agents, such as sorbitan monolaurate, may cause phlebitis or irritation of the tissues around the vein. A concentration of 10% seemed to be most suitable ; higher concentrations produced a decreased platelet-count and The most common reaction a prolonged bleeding-time. to fat emulsions was pyrexia, which was noted in about a third of the patients. The temperature began to rise just after the injection, quickly reached a peak, and within four to eight hours returned to normal, thus following the course of a typical pyrogen reaction. Anorexia, nausea, vomiting, diarrhoea, and headache occurred in some patients with a pyrexial response. A few developed lumbosacral pain, urticarial reactions, and shortness of breath. Mild anaemia has also been reported after the continued infusion of fat emulsions. Johnson and his colleagues observed that emulsions did not give pyrogen reactions if injected immediately after preparation, but did so if they had been stored, even if they had remained sterile. The emulsifying a,gents were thought to be the most probable source of pyrogeits. In no case was there evidence of renal damage or impairment of liver function. In a later study Johnson and his colleagues 15 investigated the fate of emulsified fats administered parenterally to normal people and to patients with renal insufficiency, hyperthyroidism, or cirrhosis of the liver. In normal persons 75% of the fat was removed from the circulation by the end of the infusion-that is, after two hours—but

difficulty

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11. Hinkle, L. E. jun., Wolf, S. Amer. J. med. Sci. 1949, 217, 130. 12. Hinkle L. E. jun., Evans, F. M., Wolf, S. Psychosom. Med. 1951, 13, 160, 184. 13. Van Italli, T. B., Waddell, W. R., Geyer, R. D., Stare, F. J. Arch. intern. Med. 1952, 89, 353. 14. Johnson, W. A., Freeman, S., Meyer, K. A. J. Lab. clin. Med. 1952, 39, 176. 15. Johnson, W. A., Freeman, S., Meyer, K. A. Ibid, p. 414.

the remainder was removed only. after another eight hours. Ju patients with renal impairment fat disappeared more slowly from the blood-stream ; while in thyrotoxic patients it disappeared more rapidly. The blood-fat was lower than normal in patients with cirrhosis of the liver. Dogs made diabetic with alloxan had a higher blood-fat than normal dogs or insulin-treated diabetic dogswhich is in keeping with the observation that lipæmia is common in uncontrolled diabetics. The parenteral administration of fat is not new-it was described in .Japan over thirty years ago-but difliculties of manufacture, storage, and transport of the emulsions have prevented its widespread practice. These latest studies show, however, that the injection of freshly prepared emulsions, using suitable emulsifying agents, is reasonably safe and should be considered whenever parenteral feeding has to be continued for some time. THE OXFORD SYMPOSIUM SOME years ago a, sentimental fancy led us to liken the first symposium of the Society for General Microbiology to those international disputations of the 13thcentury scholars who gathered on Mont St. Genevieve to hear Dr. Profundus and Dr. Perspicuus devoting their learning and logic to immensely interesting topics of no practical importance whatsoever. Since Oxford is to have its as an academical retreat in the thought origin of certain schoolmen who had made Paris too migration hot to hold them, it was pleasant that the society’s third symposium should draw to the banks of Isis scholars from

Brussels, Paris, Stockholm, Rome, Coimbra, Illinois, Chicago, Ontario, and even Cambridge. They came to discuss the nature of virus multiplication, and this is certainly a subject which justifies the methods of the symposium. From the time that Stanley showed the virus of tobacco mosaic to be a crystalline mass of nucleoprotein it was clear that the little which we knew (and know) about bacterial multiplication cannot be applied lock, stock, and barrel to viruses. Chance and ingenuity have provided new techniques in a field shared and not yet disputed by bacteriologist, biochemist, and and the complexity of the problem has attracted sparkling minds from all the biological sciences. Long ago in 1947 (such is the notation of these active minds) Luria brought forward evidence, suggesting that the unit of multiplication of bacteriophage is much smaller than the infecting particle which attaches itself to the host bacterium. A year later Hoyle demonstrated a similar phenomenon in influenza virus inoculated upon the allantoic membrane. Others have dotted the is, and the sum of their information indicates that the self-replicating unt is a fragment of nucleoprotein and no more. It is here that we reach the edge of the intelNo-one knows "how" larger and lectual precipice. organised bodies reproduce themselves ; but it is done by rule and some part of the mechanism we can observe. Is the multiplication of virus essentially the same process on a smaller scale and shorn of all complications ?

geneticist,

Does it depend on the host as much as on the parasite!t If A. E. Boycott had not pointed out long ago that at this level " live " and " dead " cease to carry their usual meaning, we might ask whether the replication of nucleoprotein is a chemical or a biological process. This symposium did not provide an answer, but it gave an opportunity for thoughtful men to ask the question and share surmises which they would put on paper with diffidence. It was incidentally a reminder that research is done not so much in glass and -concrete palaces as in the human forebrain. THE next session of the General Medical Council m’ll on Tuesday, May 27, at 2 P.M., when Prof. DAVID CAMPBELL, the president, will deliver an address. Tte Medical Disciplinary Committee will sit on Wednesday open

May 28,

at 2 jp.M.