29

of the isotope depends mainly on the changing pressuresinside the peritoneal cavity.In forecasting the most fruitful line of inquiry into

the cause of cancer, one man’s guess is as good as another’s.It seems not unlikely that it is to the intensive study ofcell behaviour under widely varying conditions that wecan most hopefully look for further progress. But it is

heartening to find that the B.E.C.C. is encouraging workin almost every branch of medicine and biology. Judgingfrom the projects recorded in the pages of this report,the contributions of the radiophysicist and biophysicistwill feature increasingly in this widening field of inquiry.

1. Steyn, D. G. Caffeine-containing Beverages and Human Health.Pretoria, 1954.

2. Field, J. B., Lassen, E. G., Spero, L., Link, K. P. J. biol. Chem.1944, 156, 725.

3. Roth, J. A., Ivy, A. C., Atkinson, A. J. J. Amer. med. Ass.1944, 126, 814.

4. Merendino, K. A., Judd, E. S., Baronofsky, I., Litow, S. S.,Lannin, B. G., Wangensteen, O. H. Surgery, 1945, 17, 650.

5. Judd, E. S. Bull. Amer. Coll. Surg. 1943, 28, 46.6. Roth, J. A., Ivy, A. C. Gastroenterology, 1944, 2, 274 ; Surgery,

1945, 17, 644.

THE CUP THAT CHEERS

THE popularity of caffeine-containing beverages in

many different civilisations is testimony to the solaceand stimulus which mankind derives from this delectablealkaloid. But caffeine has always had its opponents,one of whom, Professor Steyn, of the University ofPretoria, has lately marshalled the case against it.1Much of the evidence that Steyn cites is based on the

results of experiments in which large doses of caffeinewere given to laboratory animals ; and the clinical

application of such findings must always be somewhatconjectural. Thus, when dogs are given caffeine bymouth in doses of 50-400 mg. per kg. body-weightthe plasma-prothrombin time falls.2 Steyn remarksthat this " appears to have brought conclusive proofthat the ingestion of caffeine most probably aggravatesthe already serious state of thrombosis in man." Butthis conclusion is not justified on the evidence presented.Steyn is on firmer ground when he discusses the relationbetween caffeine and peptic ulcer. Roth et aL3 gave250 mg. of caffeine dissolved in 200 ml. of water tonormal persons and to ulcer patients after an overnightfast, and demonstrated a copious flow of acid gastricjuice. In most of the normal people this was short-lived, whereas in most of the patients with ulcer itcontinued longer. Similar results were obtained withcaffeine-containing beverages as ordinarily served, butthe addition of sugar and cream to coffee almost halvedthe secretory response. Merendino et awl. obtained similarresults after giving two cups of strong black coffee topeople who had fasted overnight. The experimental

production of gastric ulcers in cats and guineapigs bythe repeated daily injection of large amounts of caffeine 4-6can be dismissed by the clinician as irrelevant.

Steyn frequently sees children drinking large quantitiesof soft drinks in warm weather ; and he would like it tobe better known that many of these beverages containappreciable quantities of caffeine. The caffeine contentof one of the best known of these cola drinks is statedto be 33 mg. per bottle, and a similar well-knowndrink contains twice this amount.3 (This compares with.an estimate of 100-120 mg. of caffeine per cup of coffee,though-Steyn thinks that in South Africa the true figurefor coffee is probably below 30 mg. per cup.) The youngman admitted to hospital with a perforated peptic ulcerafter drinking 150 bottles of an iced cola drink duringfive warm August days 4 is an extreme example, and thedanger from cola drinks in this country is probably slight.Professor Steyn, however, is right in saying that in certainsoft drinks larger quantities of caffeine are consumed,especially by children, than in coffee, tea, or cocoa, andthat those parents who do not wish their children to takecaffeine should be informed of its presence in such drinks.

All this does not amount to a very damaging briefagainst caffeine-containing drinks. The only way ofproving that excessive drinking of tea and coffee isharmful is to compare the prevalence of the variousmorbid conditions to which they are alleged to give rise,in large groups of people comparable in all respects otherthan consumption of caffeine. This is the method bywhich the relation between cigarette-smoking and lungcancer was established. But immense labour would beinvolved, and the prima-facie case against caffeine doesnot seem strong enough to justify this. Meanwhile theaddicts among us will continue to rely on the reassuranceof personal experience, as did Samuel Johnson. Whenattacked by a certain Mr. Jonas Hanway for his habit oftea-drinking, Johnson, than whom " no person ever

enjoyed with more relish the infusion of that fragrantleaf," declared that Mr. Hanway had " considered theeffects of Tea upon the health of the drinker, which, Ithink, he has aggravated in the vehemence of his zeal,and which, after soliciting them by this watery luxury,year after year, I have not felt."

1. Lary, B. G., de Takats, G. J. Amer. med. Ass. 1954, 155, 10.2. Levine, S. A., Lown, B. Trans. Ass. Amer. Phycns. 1951, 64, 316.3. See also Papp, C. Brit. Heart J. 1952, 14, 250.4. Landman, M. E., Anholt, H. S., Angrist, A. Arch. intern. Med.

1949, 83, 665.5. Wade, E. G., Morgan Jones. Brit. Heart J. 1951, 13, 319.

BED REST AFTER MYOCARDIAL INFARCTION

MOST clinicians agree on the importance of bed restafter myocardial infarction, though they are mindfulthat in old persons complete immobilisation has itsown hazards from venous stasis. Lary and de Takats 1have drawn attention to arterial embolism in patientswho were on their feet shortly after a cardiac infarction.Of eight such patients, in whom embolism to the lowerlimb occurred 5-30 days after the infarct, five hadnot been kept in bed at all: and in two of these theembolus occurred within 6 days of the infarct. In four

patients the infarction was not diagnosed until afterthe embolus had occurred ; but all except two had aclinical episode consistent with infarction-either chestpain or sudden dyspnoea. One had complained only of" dizziness," while another apparently had a

" silent "

infarct following cholecystectomy. There was electro-cardiographic evidence of infarction in all but two cases.In one of these necropsy revealed multiple old infarcts.The other patient had auricular fibrillation, with noclear-cut history suggestive of infarction ; this case

did not come to necropsy, so that embolism could notdefinitely be attributed to myocardial infarction.

Failure to enforce bed rest seems to have been dueas much to non-recognition of the myocardial infarctionas to deliberate early ambulation after it. There canbe little doubt that after a major infarction bed rest forat least 6 weeks is advisable, although variations, such asLevine’s2 "chair treatment," may sometimes be of value.The report by Lary and de Takats re-emphasises thatmyocardial infarction may show itself in several differentways, particularly in the elderly, and that sudden

dyspnœa, syncope, and dizziness may be presentingsymptoms without much pain.3 Landman et al.4 foundthat 11% of 255 myocardial infarcts were " silent."It is probably rare for infarction to be unaccompaniedby any symptom whatever, although old people maygive a vague history because their memory for theevent is clouded. Infarction may present as angina ofeffort, and the sudden onset of this symptom is an

indication for rest in bed.

Lary and de Takats are not convinced of the value ofanticoagulants in the prevention of arterial embolism

following myocardial infarction. (There is a growingweight of opinion against administering anticoagulantsto patients with a clinically small infarction, short-lived pain, and no hypotension or congestive heart-

30

-failure. 6 In the " silent " or "

quiet" infarct the severitymay be difficult to gauge ; but, whatever the decisionon giving anticoagula-nts, rest in bed is essential.

6. See Lancet, 1954, i, 917.7. Doll, R., Hill, A. B. Brit. med. J. 1950, ii, 739.8. Wynder, E. L., Graham, E. A. J. Amer. med. Ass. 1950, 143, 329.9. Lancet, 1952, ii, 667.

10. Graham, E. A. Lancet, 1954, i, 1305.11. Pearl, R. Science, 1938, 87, 216.12. Doll, R., Hill, A. B. Brit. med. J. 1954, i, 1451.

SMOKING AND CANCER OF THE LUNG

THE build-up of clinical and epidemiological evidencewhich culminated- in the well-controlled studies of Dolland Bradford Hill and Wynder and Graham 8 convincedmost of us of the chill realitv of the association betweensmoking habits and disposition to cancer of the lung.But, as we have already pointed out,9 the historical orretrospective approach used in these and similar studiesis open to criticism which may appear pedantic but cannotbe ignored. Bias in the observer may have an appreciableeffect on the frequency of eliciting a history of heavysmoking ; the cancer patient himself may propose hissmoking habits as an innocent cause of his respiratorysymptoms, and these symptoms themselves may in turnchange his smoking habits. The experience of Doll andHill with patients suffering from intrathoracic growthswhich later proved to be non-malignant showed thatthese objections can be overstated. Nevertheless, since,as Dr. Graham remarks,lO human experiments are

impossible, these objections are important enough to

make " prospective " inquiries an essential step in theproof of the carcinogenic qualities of tobacco smoke.The basic idea is quite simple. A large and reasonably

homogeneous group of men are catechised about theirsmoking habits, present and past. The information isfiled and the deaths occurring in subsequent years arecollected. A comparison of the death-rates in groupswith contrasting smoking habits will then confirm or

deny the suggestions implicit in the results of the" historical " approach. In his family studies of therelation between social and personal characteristics andlongevity Pearl 11 showed that heavy smoking was

associated with excessive mortality-rates in middle life.Unfortunately he gave no analysis by cause of death, andhis genealogical methods were not, strictly speaking,prospective studies. A more satisfying development ofthis theme was reported last week by Dr. Richard Doll andProfessor Bradford Hill.12 In October, 1951, they_ askeddoctors in the United Kingdom to classify themselvesaccording to whether they were at that time smokers,whether they had given up smoking, or whether they hadnever smoked as much as one cigarette a day for as longas one year. Supplementary questions on the durationand manner of smoking tobacco were put to both presentand previous smokers. To this questionary, 24,389replies were received from men aged 35 years and overand in the twenty-nine months which have elapsed, theRegistrar-General has reported on the cause of death of789 of these doctors. Of these 789 deaths, 35 werecertified as due to lung cancer ; in 1 other, lung cancerwas a contributing cause. Inquiries from the attendingphysician showed that the diagnosis could be given withcertainty in at least 33 of these patients. Other causesof death were also separated out in the analysis, and age-standardised death-rates are given for six groups ofdiseases among non-smokers, moderate, and heavysmokers.The results are impressive. There is a clear gradient

in lung-cancer mortality from the non-smoking to heavy-smoking groups. There is also a rise, although less steep,in the death-rate from coronary thrombosis ; but no

appreciable gradient appears in other forms of cancer,other cardiovascular diseases, respiratory diseases, andall other causes of death. In short, the results of thisprospective inquiry confirm the indications so strongly

given by Hill and Doll’s previous retrospective controlledstudy, and the methodological objections already notedhave been effectively answered. With commendablecaution, the report has been called preliminary, although,with the possible exception of the trend in the respiratory-disease group, the ultimate results should differ littlefrom the pattern now observed.

In these prospective studies, publication of early resultsis important in diminishing the dangers of bias to whichthey, too, may be subject. Increasingly, a history ofheavy smoking may come to be taken by physicianscertifying death as a diagnostic indicator of lung cancer,and the association between smoking and lung-cancermortality may thus become unduly inflated. Again, thevery candour of reports such as those of Doll and Hillwho thank " the survivors of the 40,000 men andwomen " who make them possible, may in time freesome of the heavy smokers of 1951 from the tobaccohabit. For these reasons, contemporary and similarstudies in other countries are of particular value.American press accounts of a report by Dr. CuylerHammond and Dr. Daniel Horn of the American Cancer

Society to the recent meeting of the American MedicalAssociation suggest that they are reaching similarconclusions. They instituted a forward inquiry throughlay members of the American Cancer Society, who wereasked in 1951 to report on current smoking habits andsubsequent mortality experience of about ten of theirmale acquaintances between the age of 50 and 69. LikePearl, they find that the total death-rate among menbetween 50 and 64 is more than twice as high as amongnon-smokers of the same age. Like Doll and Hill, theyfind excessive death-rates for lung cancer and coronarythrombosis in the heavy-smoking group ; they suggestthat the lung-cancer death-rate is at least five times ashigh as the rate for non-smokers. On the other hand,they also report an excess in cancer of throat, kidneys,stomach, and intestinal tract which is not in line with theBritish findings. Although much larger, the Americanexperience is based on a socially less homogeneous group,which, being composed of friends of members of theAmerican Cancer Society, may contain an unduly highproportion of persons with a familial history of thatdisease. Informed comment must await the publicationof detailed results. Meanwhile, we have, in the Doll andHill report, one more sound reason for ordering the

priorities among our next New Year’s resolutions.

1. History of the Second World War. Medical Research. Editedby F. H. K. Green and G. Corell. H.M. Stationery Office,1953.

RATIONING AND SPECIAL DIETS

THIS week sees the demise of the Medical ResearchCouncil’s Food Rationing (Special Diets) AdvisoryCommittee. Formed in 1940 at the request of the

Ministry of Food, the Ministry of Health, and the Depart-ment of Health for Scotland, it was asked to advise onany modifications of the ordinary civilian rations whichmight be necessary on medical grounds for invalidsand others for whom special diets had been prescribed.Now that civilian rationing is ended, its task is

complete.No system of rationing can ever be entirely equitable.

A food that is properly regarded as a pleasant luxury forthe majority may be almost a necessity for a few. Thedietetic problems presented by clear-cut physical dis-orders such as diabetes, steatorrhoea, and tuberculosisare difficult enough ; but, when food-supplies were

limited, such indefinite conditions as food allergies andfood neuroses posed even more awkward individualproblems for which a judicious blend of scientific know-ledge and tact was needed. Some of the details of thecommittee’s work have already been recorded.!There are always in this country a considerable number

of food cranks, some of whom are well informed and