288

that nicotine acts on the heart indirectly by stimulatingsympathetic ganglia and thus raising the blood-pressure,and by increasing the discharge of catecholamines fromthe medulla and thus dilating the coronary arteries.16Nicotine acts directly on the heart, first, by stimulating thecardiac ganglia, which produces transient slowing of theheart-rate, and, secondly, by release of catecholaminesfrom the stores in the heart, which have an augmentoreffect increasing the cardiac rate and force. 1 Clinicalstudies in healthy subjects have shown that smokingincreases the coronary flow and heart-rate with a fall in

coronary vascular resistance, 18 and Irving and Yamamoto 19have demonstrated a large increase in cardiac output andstroke volume during smoking and inhaling. Studies of

patients with arteriosclerotic coronary-artery disease, onthe other hand, have shown a similar increase in cardiacoutput and blood-pressure on smoking, but with either afall or no change in coronary blood-flow ’20 which supportsthe concept of increased work with deficient vasodilatationof the arteriosclerotic coronary vessels as the cause oftobacco angina.The rarity of tobacco angina seems harder to explain.

Oram and Sowton suggest that a few individuals are

hypersensitive to tobacco, although in their patients theywere unable to demonstrate skin sensitivity either to

fractionated extracts of tobacco smoke or to tobacco itself.

INFECTION AND LEUKÆMIA

THE idea that leukaemia may be caused by a virusinfection has a long history, and much suggestive evidencehas been obtained from the study of leuksemia-likediseases in birds and rodents. Heath and Hasterlik 21 havenow reported an excessive number of cases of leukaemiaamong children in a Chicago suburban community whereat the same time there was a " rheumatic-like " illness

among other children.The suburb is Niles, a town situated in Cook County

adjacent to Chicago. Between the autumn of 1957and the summer of 1960 8 cases of leukaemia occurred

among children in the town, giving an annual incidenceof 21-3 cases per 100,000 of the population, comparedwith 4-6 cases per 100,000 in the remainder of CookCounty. Further inquiry showed that all 8 children livedin a small residential area of Niles corresponding to theRoman Catholic parish of St. John Brebeuf, and 7 of thechildren attended, or had older siblings who attended, theSt. John Brebeuf Elementary School. The cases ofleukxmia arose at the same time as a

" rheumatic-likeillness ’* affected several children attending the sameschool. Heath and Hasterlik searched the records for allsimilar cases in a wide area and found that, though ofcourse other cases of acute leukaemia had occurred, theywere scattered throughout the area without any particularpattern; only in the parish of St. John Brebeuf was therethis odd concentration. They therefore investigated thecases in considerable detail. In every instance the diag-nosis had been established by a consultant haematologist.In 6 of the 8 cases blood and marrow films were availablefor review and confirmed the diagnoses. 5 were diagnosedas stem-cell leukxmia, 2 were lymphatic leukaemia, and16. Burn, J. H. Ann. N.Y. Acad. Sci. 1960, 90, 70.17. Burn, J. H., Rand, M. J. Brit. med. J. 1958, i, 137.18. Bargeron, L. M., Jr., Ehmke, D., Gonlubol, F., Castellanos, A., Siegel,

A., Bing, J. R. Circulation, 1957, 15, 251.19. Irving, D. W., Yamamoto, T. Brit. Heart J. 1963, 25, 126.20. Regan, T. J., Hellems, H. K., Bing, J. R. Ann. N.Y. Acad. Sci. 1960, 90,

18621. Heath, C. W., Hasterlik, R. J. Amer. J. Med. 1963, 34, 796.

in 1 lymphatic leukaemia followed some months after thedetection of a lymphosarcoma of the right maxillarysinus; all 8 patients died. Extensive epidemiological andsocial inquiries disclosed no special characteristics in theaffected families:" They lived in modern, single family homes scattered widelythroughout the parish. At the time of onset of the disease theyhad been living in Niles between one and ten years, and allhad moved to Niles from northern sections of Chicago. Onlyfour of the eight children had ever travelled anywhere outsidethe Chicago area. Their fathers’ occupations varied widely,and their family origins reflected the general composition of theentire community."The " rheumatic-like illness " was also observed betweenthe autumn of 1957 and summer of 1960. 7 childrenattending St. John Brebeuf Elementary School were

affected, 1 being the elder sister of a boy who died ofleukaemia. 3 cases of adult leukaemia were detected in thisperiod, but there was no evidence of direct contact betweenthese patients and their families and the families in whichcases of childhood leukaemia were found. Levels of back-

ground radiation were tested but were quite normal.Heath and Hasterlik discuss possible ways in which

an infective agent might produce a cluster of cases ofleukaemia, but they admit that there is no firm evidence.Nevertheless, they reasonably suggest that further searchfor similar clusters might open up a new approach tounderstanding of the aetiology of leukaemia.Few similar clusters have been recorded. Wood 22

surveyed the incidence of leukaemia in West Cornwallbetween 1948 and 1959. The town of Fowey was unusualin having an exceptionally high incidence-28’8 per100,000 population per annum-which is of the sameorder as that reported from Niles. There was no evidenceof undue radiation in Fowey, and Wood remarked that,owing to the small area of the town, the patients " werenecessarily living in close relation to each other ".Another oddity was found in the town of Newquay wherethere were 17 cases, predominantly cases of chroniclymphatic leukaemia; the annual incidence worked out at13-9 per 100,000 of population-again a high figure. Onthe other hand Phillips’ 23 survey of the incidence ofleuksemia in different counties revealed no particularlyhigh incidence except in sparsely populated Mont-

gomeryshire. Perhaps the county is too large a unitfor the detection of local differences. Lee 24 has suggestedthat study of the incidence of leuksemia among thoseaged up to 19 shows a seasonal variation, with a peak inthe month of June. The incidence of leukaemia in families

: has also been studied. Bridges and Nelson 25 in Belfastrecorded 3 such families among 182 patients seen in the

, period 1948-59. In one family father and son died of the- same disease; in the other two families cousins were

v affected. Bridges and Nelson, who reviewed published: reports up to 1961, were not impressed by the evidence: that hereditary factors were responsible for these

incidents. They suggest that environmental factors might. be important, and noted our almost complete ignorance of: these factors. Further studies like that reported from

Niles, Cook County, may help to repair this ignorance.___________

Sir MAX PAGE, consulting surgeon to St. Thomas’s Hospital,, died on Aug. 1 at the age of 80.

22. Wood, E. E. Brit. med. J. 1960, i, 1760.23. Phillips, T. A. Lancet, 1959, ii, 659.24. Lee, J. A. H. Brit. med. J. 1962, i, 1737.25. Bridges, J. M., Nelson, M. G. Acta hœmat., Basel, 1961, 26, 246.