BRITISH MEDICAL JOURNAL
10 SEPTEMBER 1977
becoming ill.5 6 The problem facing doctors is that salmonellas in the gut of healthy animals may contaminate meat during slaughter and dressing. To control human salmonellosis these symptomless excreters among animals would have to be eliminated. Animal disease is caused mainly by host-adapted serotypes, such as Salmonella dublin in cattle, S gallinarum and S pullorum in poultry, S abortus-ovis in sheep, and S choleraesuis in pigs. These serotypes, which rarely infect man, accounted for 16 595 (7002" ) of the incidents in 1968-74. The decreasing incidence of salmonellosis in poultry may be attributed to a considerable reduction in infections due to S gallinarum and S pullorum. Veterinary control of clinical salmonellosis is therefore unlikely to reduce significantly human infection, even though the Zoonoses Order provides for the controlled slaughter and dressing of infected animals if there is a risk to human health.7 Likewise, a medical approach is unlikely to help the veterinarian. If all animal feed were to be heat-treated, for example, or if the proposed Protein Processing Order were to become law, the incidence of infection from host-adapted serotypes might be unchanged, as these infections are transmitted by contact between animals and rarely, if ever, by animal feed." Co-operation by both professions is clearly important; much has been done to improve this, and a recent report9 augurs well for the future. How can human salmonella infection be reduced ? Unfortunately there is no single, or simple, answer; an integrated effort is required by everyone from the animal food producer and the farmer to the cook. Prevention should undoubtedly be directed mainly towards poultry and pigs. Since the derationing of animal feed in 19533 and the subsequent development of intensive production methods, the incidence of human salmonellosis caused by poultry and pig meat has increased. S agona, S indiana, S panama, S virchow, and S 4, 12:d: have been introduced into pigs and poultry through imported or recycled contaminated food stuffs.2 10 Heat pelleting,'1-'3 especially steam pelleting,14 is the most efficient method of reducing contamination in feeding-stuffs. But this process reduces only the number of salmonellas in feeds and so cannot be relied on: the manufacture of the feed from its animal and marine protein constituents has to be controlled. Apart from fishmeal, however, the constituents of animal feed are usually byproducts of other industries, which are not concerned with producing a sterile byproduct. Reducing the storage time of skimmed milk feeding systems for pigs15 and selecting reputable sources of animal feed16 also help to reduce contamination. As infection may be introduced into poultry by birds hatched from lightly contaminated eggs,17'I special attention should be paid to feed for breeding flocks. The general adoption of chickenrearing in batches-the "all in, all out" system-has considerably reduced the transfer of infection from crop to crop. Conditions that reduce stress in animals are undoubtedly important in reducing spread of infection. These include improved design of lairages on farms19 and transport in uncrowded, correctly ventilated vehicles.20 Since 1966 the holding time at abattoirs before slaughter has been restricted to a maximum of 72 hours, and much has been done within the abattoir to reduce cross-contamination by reducing floor dressing, abolishing wiping cloths, and improving designs for washing and cleaning. In large abattoirs areas and staff associated with gut contents can be separated from other sections, but in small abattoirs this is sometimes difficult. In the processing plant, too, methods of handling and chilling the poultry must be designed to minimise cross-contamination, since this has caused several widespread outbreaks of salmonellosis.2'
653
Finally, the correct storage, thorough cooking, and, if unavoidable, adequate reheating of food, together with good hygiene in the kitchen, are especially important.22 Even if salmonella contamination of raw meats were to be eradicated, the food handler would not be absolved from practising good hygiene, as many other organisms can cause food poisoning. Nevertheless, in Britain salmonellosis accounts for about 80% of all food poisoning in which the cause is determined,4 so the incidence of food poisoning will clearly diminish if clinical and symptomless salmonella infection in poultry and pigs can be reduced. The measures we have outlined will increase the price of meat and poultry-which is the price we shall have to pay for greater safety. Sojka, W J, et al, Journal of Hygiene, Cambridge, 1977, 78, 43. Lee, J A, Journal of Hygiene, Cambridge, 1974, 72, 185. 3 McCoy, J H, J7ournal of Hygiene, Cambridge, 1975, 74, 271. 4 Vernon, E, and Tillett, H E, Public Health, London, 1974, 88, 225. 5 Smith, H W, Journal of Hygiene, Cambridge, 1960, 58, 381. 6 Gordon, R F, and Tucker, J F, British Poultry Science, 1965, 6, 251. 7 Lowes, E, The Veterinary Record, 1975, 97, 32. 8 Taylor, J, and McCoy, J H, in Food-borne Infections and Intoxications, ed H Rieman. London and New York, Academic Press, 1969. 9 Payne, D J H, and Scudamore, J M, Lancet, 1977, 1, 1249. 0 Row, B, in The Microbiological Safety of Food, eds B C Hobbs and J H B Christian, p 165. London and New York, Academic Press, 1973. Monthly Bulletin of Ministry of Health and Public Health Laboratory Service, 1961, 20, 73. 12 Edel, W, et al, Zentralblatt Veterinarmedizin, 1967(B), 14, 393. 13 Lee, J A, et al, Journal of Hygiene, Cambridge, 1972, 70, 141. 14 Kielstein, P, Barthke, W, and Schimmel, D, Monatshefte fur Veterindrmedizin, 1971, 26, 12. 15 Linton, A H, Jennett, N E, and Heard, T W, Research in Veterinary Science, 1970, 11, 452. 16 Harvey, R W S, in The Microbiological Safety of Food, eds B C Hobbs and J H B Christian, p 9. London and New York, Academic Press, 1973. 17 Borland, E D, Veterinary Record, 1975, 97, 406. 18 Marthedal, H E, in The Microbiological Safety of Food, eds B C Hobbs and J H B Christian, p 41. London and New York, Academic Press, 1973. 9 Williams, E F, and Spencer, R, in The Microbiological Safety of Food, eds B C Hobbs and J H B Christian, p 41. London and New York, Academic Press, 1973. 20 Ministry of Agriculture, Fisheries and Food and Public Health Laboratory Service, Journal of Hygiene, Cambridge, 1965, 63, 223. 21 Public Health Laboratory Service, British Medical Journal, 1975, 4, 529. 22 British Medical_Journal, 1976, 2, 341. 1
2
Blood culture in the old In the larger American hospitals it has long been common practice to perform daily blood cultures on patients who elsewhere would be submitted to only one or perhaps even none at all. The changing causes of bacteraemia and the techniques and varied results of blood culture have been described in detail in Sonnenwirth's excellent book.' Even so, clinical acumen can reduce the numbers of such cultures likely to be most unprofitable and at the same time ensure that they are not omitted when the result may sometimes be of vital importance. Blood culture has been little studied in geriatrics. The geriatric unit at Northwick Park Hospital has a possibly exceptional opportunity for performing such studies, since there is usually no waiting list, and many of the patients investigated there by M J Denham and G S Goodwin2 were acutely ill. Blood was "usually taken by a phlebotomist" (it is interesting that the meaning of this archaic word should now have been transferred from the scalpel to the needle), and fluid cultures were made providing the three necessary atmospheres, with subcultivation at four intervals up to 14 days. Some patients had only one culture and others up to six or seven;
654
most positive results occurred in the first three cultures. Over 14 months 498 blood samples were cultured from 295 patients; 49 cultures were positive but only 27 of these were considered significant; of the remainder 16 grew Staphylococcus albus and six other commensals. The principal bacteria found in the cultures that were considered significantly positive were pneumococci in seven, Staph aureus in six, Streptococcus viridans in four, and "Proteus vulgaris" in three (this is an uncommon species, since most infections are due to P mirabilis). Clinical diagnoses are separately listed and not related to the bacteriological diagnoses. Positive cultures were obtained in six out of 95 patients with respiratory infection, four out of 28 with suspected bacterial endocarditis, five out of 32 with "non-specific malaise," and in one or two with recent onset of confusion, uncontrolled diabetes, and miscellaneous septic states. The authors emphasise that clinical signs of septicaemia, including fever, shock, and oliguria, were often lacking. Over half the patients with significant bacteraemia died, with the important exception of those with pneumococcal infection, all of whom survived. Several lessons may be learnt from these results. Firstly, bacterial endocarditis should be strongly suspected in any elderly patient with a heart murmur, even in the absence of all other signs. A second, even more important lesson is the value of blood culture in diagnosing pneumococcal lung infection, for only 22 of these 95 patients, including only one of the six with pneumococcal bacteraemia, had a positive result on sputum culture. As the authors admit, there may have been other reasons for this, such as a poor technique in collecting the sputum; and it must be admitted that poor cultural technique may also have been a factor. It would be interesting to know in how many of these 95 specimens intraperitoneal mouse inoculation would have provided the answer-and provided it much more rapidly than ordinary cultivation. Lastly, it is important to recognise that in the elderly such nondescript complaints as mere "malaise" may result from bacteraemia. This is clearly a field in which blood culture may be the only means of reaching a diagnosis. 1 2
Sonnenwirth, A C, ed, Bacteremia, Laboratory and Clinical Studies. Springfield, Thomas, 1973. Denham, M J, and Goodwin, G S, Age and Ageing, 1977, 6, 85.
Immunological deficiency and the risk of cancer We now know that a child with a primary immune deficiency disease has a hundredfold increase in the incidence of cancer over that in a population of normal children. Dr Robert Good of the Memorial Hospital, New York, announced at a symposium on lymphomas held in Paris this June that 227 (9%0) cases of malignant tumours had now developed among the 2500 patients known to have congenital immune deficiency diseases. This special group of immune deficiency diseases, lying as they do at the intersection of immunology and carcinogenesis research, may hold the key to several of the contemporary questions about the causes of cancer. The high risk of cancer in immune deficiency diseases presents researchers with the challenge of designing a study that will identify one of several factors that increases this risk. Meanwhile, laboratory-based
BRITISH MEDICAL JOURNAL
10 SEPTEMBER 1977
scientists are conducting studies that may one day enable some form of biological engineering to correct the fundamental fault in the immune system or provide an acceptable healthy line of cells to compensate for those that are defective. The distribution of tumour types in immune deficiency diseases does not follow the pattern we might expect if the risk of developing cancer was non-specifically increased in these children. Of the 151 tumours recorded in the immune deficiency diseases registry in 1973,1 2 over half (88) were lymphoreticular tumours. This group of tumours were predominant in all the main types of immune deficiency diseaseisolated deficiency, Wiskott-Aldrich syndrome, ataxia telangiectasia, common variable hypogammaglobulinaemia, and severe combined immunodeficiency. In ataxia telangiectasia the risk of cancer is as high as 10%. On the other hand, the incidence of tumours of the central nervous system, bones, and other sites such as the kidney is much lower than would be expected if the deficiency disease simply generally increased the risk of developing cancer.3 4 Leukaemias, for example, are only half as common as would be expected from their normal percentage contribution to the spectrum of children's tumours. The distribution of subgroups of lymphoreticular cancers is also abnormal. Dr Good estimated that in an unselected population of such cancers 12% would be B-cell type, 18% T-cell type, and 7000 classified as nul. In patients with immune deficiency diseases, however, 78% of these cancers were B-cell type and 22% T-cell type, which again shows the special biological selection operating in these conditions. Another view of the relation of immunodepression and cancer comes as an unwelcome consequence of replacing diseased organs by grafting, which necessitates chronic immunosuppression to prevent graft rejection. Penn5 has recently reviewed this phenomenon and calculated that the risk of cancer is increased 10 to 100 times by iatrogenic immunosuppression. In patients with such secondary immunodeficiency, epithelial tumours accounted for 67% of the cancers, with the lip, skin, and cervix being most often affected. Hoover and Fraumeni,6 reviewing 6297 patients given kidney transplants in 1951-71, calculated that their risk of developing lymphoma was 30-40 times the expected risk in age-matched controls. We have no evidence that tissues from patients with immune deficiency diseases show an increased susceptibility to carcinogenic viruses, such as neoplastic transformation by SV40 virus,7 though fibroblasts from patients with Fanconi's syndrome8 and Down's syndrome9 do show an increased susceptibility. Some workers suspect that chromosome 14 may be abnormal in patients with immune deficiency diseases but this needs further study. Indeed, hard evidence on how the basic defect of an immune deficiency syndrome or secondary immunosuppression is linked to the induction of cancer is still lacking. The preferential development of certain types of tumours weighs against a glib explanation that the cancers arise because of the lack of protection from an immunosurveillance system. Kersey, J H, Spector, B D, and Good, R A, International J7ournal of Cancer, 1973, 12, 333. 2 Kirkpatrick, C H, Birth Defects, Original Article Series, 1976, 12, 61. 3Kersey, J H, Spector, B D, and Good, R A,J'ournal of Pediatrics, 1974, 84, 263. 4Miller, R W, J'ournal of Pediatrics, 1969, 75, 685. 5 Penn, I, Cancer, 1974, 34 (suppl), 858. 6 Hoover, R, and Fraumeni, J F, Lancet, 1973 2, 55. 7 Kersey, J H, Gatti, R A, and Good, R A, Proceedings of the National Academy of Science, USA, 1972, 69, 980. 8 Todaro, G J, Green, H, and Swift, M R, Science, 1966, 153, 1252. 9 Todaro, G J, and Martin, G, Proceedings of the Society for Experimental Biology and Medicine, 1967, 124, 1232.
10 SEPTEMBER 1977
becoming ill.5 6 The problem facing doctors is that salmonellas in the gut of healthy animals may contaminate meat during slaughter and dressing. To control human salmonellosis these symptomless excreters among animals would have to be eliminated. Animal disease is caused mainly by host-adapted serotypes, such as Salmonella dublin in cattle, S gallinarum and S pullorum in poultry, S abortus-ovis in sheep, and S choleraesuis in pigs. These serotypes, which rarely infect man, accounted for 16 595 (7002" ) of the incidents in 1968-74. The decreasing incidence of salmonellosis in poultry may be attributed to a considerable reduction in infections due to S gallinarum and S pullorum. Veterinary control of clinical salmonellosis is therefore unlikely to reduce significantly human infection, even though the Zoonoses Order provides for the controlled slaughter and dressing of infected animals if there is a risk to human health.7 Likewise, a medical approach is unlikely to help the veterinarian. If all animal feed were to be heat-treated, for example, or if the proposed Protein Processing Order were to become law, the incidence of infection from host-adapted serotypes might be unchanged, as these infections are transmitted by contact between animals and rarely, if ever, by animal feed." Co-operation by both professions is clearly important; much has been done to improve this, and a recent report9 augurs well for the future. How can human salmonella infection be reduced ? Unfortunately there is no single, or simple, answer; an integrated effort is required by everyone from the animal food producer and the farmer to the cook. Prevention should undoubtedly be directed mainly towards poultry and pigs. Since the derationing of animal feed in 19533 and the subsequent development of intensive production methods, the incidence of human salmonellosis caused by poultry and pig meat has increased. S agona, S indiana, S panama, S virchow, and S 4, 12:d: have been introduced into pigs and poultry through imported or recycled contaminated food stuffs.2 10 Heat pelleting,'1-'3 especially steam pelleting,14 is the most efficient method of reducing contamination in feeding-stuffs. But this process reduces only the number of salmonellas in feeds and so cannot be relied on: the manufacture of the feed from its animal and marine protein constituents has to be controlled. Apart from fishmeal, however, the constituents of animal feed are usually byproducts of other industries, which are not concerned with producing a sterile byproduct. Reducing the storage time of skimmed milk feeding systems for pigs15 and selecting reputable sources of animal feed16 also help to reduce contamination. As infection may be introduced into poultry by birds hatched from lightly contaminated eggs,17'I special attention should be paid to feed for breeding flocks. The general adoption of chickenrearing in batches-the "all in, all out" system-has considerably reduced the transfer of infection from crop to crop. Conditions that reduce stress in animals are undoubtedly important in reducing spread of infection. These include improved design of lairages on farms19 and transport in uncrowded, correctly ventilated vehicles.20 Since 1966 the holding time at abattoirs before slaughter has been restricted to a maximum of 72 hours, and much has been done within the abattoir to reduce cross-contamination by reducing floor dressing, abolishing wiping cloths, and improving designs for washing and cleaning. In large abattoirs areas and staff associated with gut contents can be separated from other sections, but in small abattoirs this is sometimes difficult. In the processing plant, too, methods of handling and chilling the poultry must be designed to minimise cross-contamination, since this has caused several widespread outbreaks of salmonellosis.2'
653
Finally, the correct storage, thorough cooking, and, if unavoidable, adequate reheating of food, together with good hygiene in the kitchen, are especially important.22 Even if salmonella contamination of raw meats were to be eradicated, the food handler would not be absolved from practising good hygiene, as many other organisms can cause food poisoning. Nevertheless, in Britain salmonellosis accounts for about 80% of all food poisoning in which the cause is determined,4 so the incidence of food poisoning will clearly diminish if clinical and symptomless salmonella infection in poultry and pigs can be reduced. The measures we have outlined will increase the price of meat and poultry-which is the price we shall have to pay for greater safety. Sojka, W J, et al, Journal of Hygiene, Cambridge, 1977, 78, 43. Lee, J A, Journal of Hygiene, Cambridge, 1974, 72, 185. 3 McCoy, J H, J7ournal of Hygiene, Cambridge, 1975, 74, 271. 4 Vernon, E, and Tillett, H E, Public Health, London, 1974, 88, 225. 5 Smith, H W, Journal of Hygiene, Cambridge, 1960, 58, 381. 6 Gordon, R F, and Tucker, J F, British Poultry Science, 1965, 6, 251. 7 Lowes, E, The Veterinary Record, 1975, 97, 32. 8 Taylor, J, and McCoy, J H, in Food-borne Infections and Intoxications, ed H Rieman. London and New York, Academic Press, 1969. 9 Payne, D J H, and Scudamore, J M, Lancet, 1977, 1, 1249. 0 Row, B, in The Microbiological Safety of Food, eds B C Hobbs and J H B Christian, p 165. London and New York, Academic Press, 1973. Monthly Bulletin of Ministry of Health and Public Health Laboratory Service, 1961, 20, 73. 12 Edel, W, et al, Zentralblatt Veterinarmedizin, 1967(B), 14, 393. 13 Lee, J A, et al, Journal of Hygiene, Cambridge, 1972, 70, 141. 14 Kielstein, P, Barthke, W, and Schimmel, D, Monatshefte fur Veterindrmedizin, 1971, 26, 12. 15 Linton, A H, Jennett, N E, and Heard, T W, Research in Veterinary Science, 1970, 11, 452. 16 Harvey, R W S, in The Microbiological Safety of Food, eds B C Hobbs and J H B Christian, p 9. London and New York, Academic Press, 1973. 17 Borland, E D, Veterinary Record, 1975, 97, 406. 18 Marthedal, H E, in The Microbiological Safety of Food, eds B C Hobbs and J H B Christian, p 41. London and New York, Academic Press, 1973. 9 Williams, E F, and Spencer, R, in The Microbiological Safety of Food, eds B C Hobbs and J H B Christian, p 41. London and New York, Academic Press, 1973. 20 Ministry of Agriculture, Fisheries and Food and Public Health Laboratory Service, Journal of Hygiene, Cambridge, 1965, 63, 223. 21 Public Health Laboratory Service, British Medical Journal, 1975, 4, 529. 22 British Medical_Journal, 1976, 2, 341. 1
2
Blood culture in the old In the larger American hospitals it has long been common practice to perform daily blood cultures on patients who elsewhere would be submitted to only one or perhaps even none at all. The changing causes of bacteraemia and the techniques and varied results of blood culture have been described in detail in Sonnenwirth's excellent book.' Even so, clinical acumen can reduce the numbers of such cultures likely to be most unprofitable and at the same time ensure that they are not omitted when the result may sometimes be of vital importance. Blood culture has been little studied in geriatrics. The geriatric unit at Northwick Park Hospital has a possibly exceptional opportunity for performing such studies, since there is usually no waiting list, and many of the patients investigated there by M J Denham and G S Goodwin2 were acutely ill. Blood was "usually taken by a phlebotomist" (it is interesting that the meaning of this archaic word should now have been transferred from the scalpel to the needle), and fluid cultures were made providing the three necessary atmospheres, with subcultivation at four intervals up to 14 days. Some patients had only one culture and others up to six or seven;
654
most positive results occurred in the first three cultures. Over 14 months 498 blood samples were cultured from 295 patients; 49 cultures were positive but only 27 of these were considered significant; of the remainder 16 grew Staphylococcus albus and six other commensals. The principal bacteria found in the cultures that were considered significantly positive were pneumococci in seven, Staph aureus in six, Streptococcus viridans in four, and "Proteus vulgaris" in three (this is an uncommon species, since most infections are due to P mirabilis). Clinical diagnoses are separately listed and not related to the bacteriological diagnoses. Positive cultures were obtained in six out of 95 patients with respiratory infection, four out of 28 with suspected bacterial endocarditis, five out of 32 with "non-specific malaise," and in one or two with recent onset of confusion, uncontrolled diabetes, and miscellaneous septic states. The authors emphasise that clinical signs of septicaemia, including fever, shock, and oliguria, were often lacking. Over half the patients with significant bacteraemia died, with the important exception of those with pneumococcal infection, all of whom survived. Several lessons may be learnt from these results. Firstly, bacterial endocarditis should be strongly suspected in any elderly patient with a heart murmur, even in the absence of all other signs. A second, even more important lesson is the value of blood culture in diagnosing pneumococcal lung infection, for only 22 of these 95 patients, including only one of the six with pneumococcal bacteraemia, had a positive result on sputum culture. As the authors admit, there may have been other reasons for this, such as a poor technique in collecting the sputum; and it must be admitted that poor cultural technique may also have been a factor. It would be interesting to know in how many of these 95 specimens intraperitoneal mouse inoculation would have provided the answer-and provided it much more rapidly than ordinary cultivation. Lastly, it is important to recognise that in the elderly such nondescript complaints as mere "malaise" may result from bacteraemia. This is clearly a field in which blood culture may be the only means of reaching a diagnosis. 1 2
Sonnenwirth, A C, ed, Bacteremia, Laboratory and Clinical Studies. Springfield, Thomas, 1973. Denham, M J, and Goodwin, G S, Age and Ageing, 1977, 6, 85.
Immunological deficiency and the risk of cancer We now know that a child with a primary immune deficiency disease has a hundredfold increase in the incidence of cancer over that in a population of normal children. Dr Robert Good of the Memorial Hospital, New York, announced at a symposium on lymphomas held in Paris this June that 227 (9%0) cases of malignant tumours had now developed among the 2500 patients known to have congenital immune deficiency diseases. This special group of immune deficiency diseases, lying as they do at the intersection of immunology and carcinogenesis research, may hold the key to several of the contemporary questions about the causes of cancer. The high risk of cancer in immune deficiency diseases presents researchers with the challenge of designing a study that will identify one of several factors that increases this risk. Meanwhile, laboratory-based
BRITISH MEDICAL JOURNAL
10 SEPTEMBER 1977
scientists are conducting studies that may one day enable some form of biological engineering to correct the fundamental fault in the immune system or provide an acceptable healthy line of cells to compensate for those that are defective. The distribution of tumour types in immune deficiency diseases does not follow the pattern we might expect if the risk of developing cancer was non-specifically increased in these children. Of the 151 tumours recorded in the immune deficiency diseases registry in 1973,1 2 over half (88) were lymphoreticular tumours. This group of tumours were predominant in all the main types of immune deficiency diseaseisolated deficiency, Wiskott-Aldrich syndrome, ataxia telangiectasia, common variable hypogammaglobulinaemia, and severe combined immunodeficiency. In ataxia telangiectasia the risk of cancer is as high as 10%. On the other hand, the incidence of tumours of the central nervous system, bones, and other sites such as the kidney is much lower than would be expected if the deficiency disease simply generally increased the risk of developing cancer.3 4 Leukaemias, for example, are only half as common as would be expected from their normal percentage contribution to the spectrum of children's tumours. The distribution of subgroups of lymphoreticular cancers is also abnormal. Dr Good estimated that in an unselected population of such cancers 12% would be B-cell type, 18% T-cell type, and 7000 classified as nul. In patients with immune deficiency diseases, however, 78% of these cancers were B-cell type and 22% T-cell type, which again shows the special biological selection operating in these conditions. Another view of the relation of immunodepression and cancer comes as an unwelcome consequence of replacing diseased organs by grafting, which necessitates chronic immunosuppression to prevent graft rejection. Penn5 has recently reviewed this phenomenon and calculated that the risk of cancer is increased 10 to 100 times by iatrogenic immunosuppression. In patients with such secondary immunodeficiency, epithelial tumours accounted for 67% of the cancers, with the lip, skin, and cervix being most often affected. Hoover and Fraumeni,6 reviewing 6297 patients given kidney transplants in 1951-71, calculated that their risk of developing lymphoma was 30-40 times the expected risk in age-matched controls. We have no evidence that tissues from patients with immune deficiency diseases show an increased susceptibility to carcinogenic viruses, such as neoplastic transformation by SV40 virus,7 though fibroblasts from patients with Fanconi's syndrome8 and Down's syndrome9 do show an increased susceptibility. Some workers suspect that chromosome 14 may be abnormal in patients with immune deficiency diseases but this needs further study. Indeed, hard evidence on how the basic defect of an immune deficiency syndrome or secondary immunosuppression is linked to the induction of cancer is still lacking. The preferential development of certain types of tumours weighs against a glib explanation that the cancers arise because of the lack of protection from an immunosurveillance system. Kersey, J H, Spector, B D, and Good, R A, International J7ournal of Cancer, 1973, 12, 333. 2 Kirkpatrick, C H, Birth Defects, Original Article Series, 1976, 12, 61. 3Kersey, J H, Spector, B D, and Good, R A,J'ournal of Pediatrics, 1974, 84, 263. 4Miller, R W, J'ournal of Pediatrics, 1969, 75, 685. 5 Penn, I, Cancer, 1974, 34 (suppl), 858. 6 Hoover, R, and Fraumeni, J F, Lancet, 1973 2, 55. 7 Kersey, J H, Gatti, R A, and Good, R A, Proceedings of the National Academy of Science, USA, 1972, 69, 980. 8 Todaro, G J, Green, H, and Swift, M R, Science, 1966, 153, 1252. 9 Todaro, G J, and Martin, G, Proceedings of the Society for Experimental Biology and Medicine, 1967, 124, 1232.
