- Email: [email protected]
LEVAMISOLE
750
However, the cells display a growth pattern characteristic of cultured human B lymphoid cells: they grow in large clumps. The cultured lymphoid cells have extremely long surface projections and produce mature virions of a herpestype virus, probably those of the Epstein-Barr virus (see accompanying figure). It is known that this virus selectively transforms only B but not T human llmphocytes.10 Thus, the cells obtained in permanent culture from the spleen of a patient with L.R.E. appear and behave like B lymphocytes but display unusually long surface villi. University of Texas System Cancer Center, JOSEPH G. SINKOVICS M. D. Anderson Hospital, CHIU-HWA WANG. Houston, Texas 77025, U.S.A. Veterans Administration Hospital and Baylor College of Medicine, Houston, Texas 77025, U.S.A.
FERENC GYÖRKEY.
THE CONSULTANTS’ CONTRACT SiR,—The proposals put forward by the Secretary of State on Dec. 2011 seem on the surface to be good for the N.H. S. However, even if consultants were able to give more time to the N.H.S. as a result of this reshaped contract, there is not money available to provide the operating suites and outpatient consulting-rooms necessary. The situation is, however, more serious than this because by the Secretary of State’s proposals the scene would be set for changes of pattern of consultant activity that would worsen both the short and long term manpower situation so far as service and postgraduate education is concerned. How could the profession’s negotiators have accepted this at a time when there is insufficient money to maintain even the agreed 4% annual increase in consultant establishment and when, because of the continued effect of the Willink recommendation, the hospital service is more dependent on overseas doctors than at any time in its history ? The principles behind the Secretary of State’s proposals remain and it is for this reason that impasse has been reached. Editorial pens move people. Perhaps yours can be instrumental in urging the Government and profession to jointly seek a judicial definition of what the consultant contract
really
means.
Hellingly Hospital, Hailsham,
RONALD MAGGS,
Sussex BN27 4ER.
Whole-time consultant.
SiR,-In view of the escalating and irresponsible sanctions by some N.H.S. consultants, I call upon my fellow retired consultants to report for unpaid part-time duty, either at their former place of work or at the nearest hospital that needs them. In this way we may hope to salvage what is left of our reputation at home and abroad and to break the stranglehold that threatens our patients. llA Acol Road, London NW6 3AA.
L. S. MICHAELIS.
SIR,-It is with interest that we read Mr Robinson’s letter (March 15, p. 626). Do you, Sir, regard The Lancet " as essentially a consultants’ journal "? M. G. BAMBER H. R. L. BISHOP-CORNET Medical Students’ Residence, A. F. MANLEY Alder Hey Hospital, SUSAN M. MURRAY West Derby, M. WARMINGER. 12. Liverpool "
** *No: we do not look upon this journal as being essentially " for (or against, for that matter !) any parti-
cular group of readers.-ED. L. 10. Pattengale, P. K., Smith, R. W., Gerber, P. Lancet, 1973, ii, 93. 11. See Lancet, Jan. 11, 1975, p. 92.
DIOGENES SYNDROME
SIR,-I should like to agree with some of the points made in this correspondence (March 1, p. 515, March 15, p. 627). Fire hazards to the patient and to neighbours can be very real, and can often ultimately tip the scales towards compulsory removal. One must also add the danger of gassing and explosions if the house has gas appliances. I cannot, however, agree that one must always respect the wish of the individual to neglect himself even unto death. I have seen some patients who did not do well in a geriatric unit or eventide home, but I have also seen many take on a new and happy life after admission to such units, particularly if the units are stimulating and well run. In Scotland, such cases are rarely handled by compulsory admission powers under the Mental Health (Scotland) Act 1960. More appropriate (and .effective) is Section 47 of the National Assistance Act 1948 (" unable to devote to themselves proper care and attention, and not receiving it from others... " &c.) or the National Assistance (Amendment) Act 1951. Non-conformity in itself is never a sure sign of psychiatric
disorder and whether or not one invokes
compulsory powers depend on as accurate a psychiatric assessment as possible. Personality inventories and psychometric I assessments, fear, have no place in helping the clinician to make up his mind in the patient’s home. Repeated visits are nearly always necessary before an accurate may well
be made. The decision on the correct course of action will always be difficult, but I feel that if the physician approaches each case with an open mind and weighs all the clinical, social, and domestic factors carefully, he will usually take the action which is in the patient’s best interests. assessment can
Department of Community Medicine, Ruchill Hospital, Glasgow G20 9NB.
H. MACANESPIE.
LEVAMISOLE
SIR,—Your editorial (Jan. 18, p. 151) calls for controlled clinical trials of levamisole, and at least two centres are already using it in the treatment of human malignancies.I,2 We wish to support the caution sounded by Dr Hopper and others,3 regarding the experimental evidence for tumour inhibition by levamisole. In our experience with levamisole (L-tetramisole), and with the racemic mixture (D-L-tetramisole) to which greater activity has been attributed,4the drug did not stimulate humoral or cellular immune responsiveness. We found no evidence of altered humoral antibody response to sheep erythrocytes injected in groups of mice receiving 1-25 mg. per kg. body-weight intraperitoneally of levamisole over various time schedules.- We did not observe either immunosuppression associated with drug therapy before antigen challenge, or immunostimulation associated with drug administration with or soon after antigen challenge, as reported by others.4 Similarly, we found no evidence of accelerated rejection of tail skin grafts in mice treated by similar schedules, which also failed to inhibit growth of a transplanted fat tumour. In this last experiment, rats immunised with irradiated Walker 256 tumour cells or inoculated with viable tumour received the drug (2-5 mg. In-vitro assays per kg. body-weight) intraperitoneally. showed no increase in serum-antibody potency or spleencell cytotoxicity at different times following tumour Webster, D. J. T., Hughes, L. E. Lancet, Feb. 15, 1975, p. 389. Amery, W. ibid. Hopper, D. G., Pimm, M. V., Baldwin, R. W. ibid. March 8, 1975, p. 574. 4. Renoux, G., Renoux, M. J. Immun. 1974, 113, 779. 1. 2. 3.
751
challenge. In contrast, retardation of the growth of a rat epithelioma has been achieved by other non-specific immunostimulants, such as killed Brucella abortus. If levamisole is an immunostimulant, we do not know what it might stimulate, and the possibility of exciting an undesirable kind of immunological reaction demands further investigation in animal models before opening the floodgates of necessarily less controllable clinical trials. Department of Pathology and Immunology, Monash University Medical School, Melbourne, Australia 3181.
G. R. FLANNERY
J. M. ROLLAND R. C. NAIRN.
PERSON-TO-PERSON TRANSMISSION OF ENTERIC BACTERIAL INFECTION SIR,-Dr Steere and his colleagues (Feb. 8, p. 319) have demonstrated person-to-person spread of salmonellosis in cases where predisposition due to reduced gastric activity or previous treatment with antibiotics was precluded. This faces the epidemiologist once more with the question why challenges with very low concentrations of enteric pathogenic bacteria can occasionally trigger disease in persons, whereas, when the same organisms are absorbed with food, doses well over 103 colony-forming units seem to be required.l Outbreaks of salmonellosis II-ó and shigellosis 6-10 transmitted in drinking-water that was certainly not grossly contaminated have presented similar
healthy
questions. Such questions have prompted us to carry out some investigations of the kinetics of the emptying of the stomach, using a 99mTc-colloid dispersion in water, its fate being studied with a gamma camera on line with a computer. This revealed that, in healthy individuals, small amounts of water (up to 50 ml.) taken between meals pass the pyloric area with very little delay. When such small volumes of liquid substrate contain enteric pathogens, these bacteria are hardly exposed to the bactericidal effect of gastric juice and hence reach the duodenum in virtually the same numbers as ingested. In this way very small numbers of cells may lead to disease. However, when the same bacteria are absorbed with solid food, intragastric-retention times are considerable. This results in a dramatic reduction of viable bacterial cells, at least in normoacidic subjects. In this instance very high numbers of cells have to be absorbed to allow at least a few to penetrate the duodenal and lower areas. The infecting dose of given enteropathogenic bacteria thus depends greatly on the carrier wherein the bacteria are contained, particularly water versus solid foods. Person-toperson spread of such pathogens might result from a saliva-borne infection secondary to transmission by the contaminated hand, similar to the triggering of enteric bacterial disease resulting from the consumption of relatively, small volumes of only very sparsely polluted drinking-water. Institute for Food of Animal
Origin, State University of Utrecht, Netherlands.
D. A. A. MOSSEL H. Y. OEI.
Armstrong, R. W., Fodor, T., Curling, G. T., Cohen, A. B., Morris, G. K., Martin, W. T., Feldman, J. Am. J. Epidem. 1970, 91, 300. 2. Greenberg, A. E., Ongerth, J. H. J. Am. Water Works Ass. 1966, 58, 1145. 3. Price, J., Carter, H. R. Publ. Hlth Rep., Wash. 1967, 82, 551. 4. Renteln, H. A., Himman, A. R. Am. J. Epidem. 1967, 86, 1. 5. Boring, J. R., Martin, W. T., Elliot, L. M. ibid. 1971, 93, 49. 6. Drachman, R. H., Payne, F. J., Jenkins, A. A. Am. J. Hyg. 1960, 72, 321. 7. Green, D. M., Scott, S. S., Mowat, D. A. E., Shearer, E. J. M., Thomson, J. M. J. Hyg., Camb. 1968, 66, 383. 8. Schiff, S., Landiak, E., Hinman, A. R., Altman, R. Morbid. Mortal. Wkly Rep. 1971, 20, 389. 9. Dorothy, L., Voelker, E. C., Bridson, K., Lindell, S., Hausler, W., Kosuri, M. R., Carr, F., Reeve, A. M. ibid. 1973, 22, 21. 10. Burr, J., Pearson, M., Quick, R., Saslaw, M. S., Craun, G. ibid. 1974, 23, 134.
BLOOD-LEAD LEVELS, BEHAVIOUR, AND INTELLIGENCE SIR,-Dr McCabe’s letter (Oct. 12, p. 896) criticising the Center for Disease Control’s report of psychological deficit in children appears to be an exception to an observation we and others have made. We have noted that reports and commentary on lead toxicity tend to sharply divide between those who are alarmed that " low level lead " exposure is accompanied by adverse health effects, particularly in neuropsychological performance, and those who argue that no case has been made for low-level lead exposure as a hazard. We could find no statement, report, or study by an industry-sponsored scientist, whether in-house grantee, or academic consultant, which frankly acknowledges that low-level exposure is hazardous. Those reports of toxicity due to low-level lead exposure, on the other hand, tend to from departments of public health, paediatrics, or environmental science. This observation appears well literature and by views expressed the recent supported by at three major meetings. 1-3 The association between nature of sponsorship and position on low-level lead toxicity appears challenged by Dr McCabe’s letter. Dr McCabe cited his affiliation as an academic department of paediatrics in Wisconsin, but argued that low-level-lead effects have not been demonstrated. We find, however, that his text was first published almost verbatim as an International Lead Zinc Research Organisation In-House Report, dated "July 16, 1974. In that report, the face sheet lists him as Edward McCabe, Pediatric Consultant, ILZRO (International Lead Zinc Research Organisation ". It is not our interest to question Dr McCabe’s intent. That the lead industry supports research on the health effects of its products, and hires medical consultants for opinions, seems only proper. That these consultants acknowledge industry support when entering industry-sponsored comment into the scientific arena, seems to us not only proper, but obligatory.
come
Harvard Medical School, and Children’s Hospital Medical
Center, Longwood Avenue, Boston, Massachusetts 02115,
300
U.S.A.
Case Western Reserve University University of Illinois, School of Public Health. Harvard Medical School.
Hospital for Sick Children, Toronto.
HERBERT L. NEEDLEMAN. SAMUEL EPSTEIN. BERTRAM CARNOW.
JOHN SCANLON. DAVID PARKINSON.
Industrial Union Department, AFL-CIO.
SHELDON SAMUELS.
Oil, Chemistry and Atomic Workers.
ANTHONY MAZZOCHI.
State University of New York, Downstate.
OLIVER DAVID.
1.
** *
We showed this letter to Dr McCabe, whose follows.-ED. L.
reply
letter signed by Dr Needleman and others scientific rebuttal to my letter, which contained
SIR,-The offers
no
Symposium on Health Effects of Lead. Congress of European Communities, Environmental Protection Agency, Amsterdam, 1972. 2. Low Level Lead Exposure. National Institute of Environmental Health Science, Environmental Protection Agency. Raleigh, North Carolina, 1973. Environmental Health Perspectives, no. 7, May, 1974. 3. International Symposium, Recent Advances in the Assessment of the Health Effects of Environmental Pollution, W.H.O., C.E.C., E.P.A., Paris, 1974. 1. International
However, the cells display a growth pattern characteristic of cultured human B lymphoid cells: they grow in large clumps. The cultured lymphoid cells have extremely long surface projections and produce mature virions of a herpestype virus, probably those of the Epstein-Barr virus (see accompanying figure). It is known that this virus selectively transforms only B but not T human llmphocytes.10 Thus, the cells obtained in permanent culture from the spleen of a patient with L.R.E. appear and behave like B lymphocytes but display unusually long surface villi. University of Texas System Cancer Center, JOSEPH G. SINKOVICS M. D. Anderson Hospital, CHIU-HWA WANG. Houston, Texas 77025, U.S.A. Veterans Administration Hospital and Baylor College of Medicine, Houston, Texas 77025, U.S.A.
FERENC GYÖRKEY.
THE CONSULTANTS’ CONTRACT SiR,—The proposals put forward by the Secretary of State on Dec. 2011 seem on the surface to be good for the N.H. S. However, even if consultants were able to give more time to the N.H.S. as a result of this reshaped contract, there is not money available to provide the operating suites and outpatient consulting-rooms necessary. The situation is, however, more serious than this because by the Secretary of State’s proposals the scene would be set for changes of pattern of consultant activity that would worsen both the short and long term manpower situation so far as service and postgraduate education is concerned. How could the profession’s negotiators have accepted this at a time when there is insufficient money to maintain even the agreed 4% annual increase in consultant establishment and when, because of the continued effect of the Willink recommendation, the hospital service is more dependent on overseas doctors than at any time in its history ? The principles behind the Secretary of State’s proposals remain and it is for this reason that impasse has been reached. Editorial pens move people. Perhaps yours can be instrumental in urging the Government and profession to jointly seek a judicial definition of what the consultant contract
really
means.
Hellingly Hospital, Hailsham,
RONALD MAGGS,
Sussex BN27 4ER.
Whole-time consultant.
SiR,-In view of the escalating and irresponsible sanctions by some N.H.S. consultants, I call upon my fellow retired consultants to report for unpaid part-time duty, either at their former place of work or at the nearest hospital that needs them. In this way we may hope to salvage what is left of our reputation at home and abroad and to break the stranglehold that threatens our patients. llA Acol Road, London NW6 3AA.
L. S. MICHAELIS.
SIR,-It is with interest that we read Mr Robinson’s letter (March 15, p. 626). Do you, Sir, regard The Lancet " as essentially a consultants’ journal "? M. G. BAMBER H. R. L. BISHOP-CORNET Medical Students’ Residence, A. F. MANLEY Alder Hey Hospital, SUSAN M. MURRAY West Derby, M. WARMINGER. 12. Liverpool "
** *No: we do not look upon this journal as being essentially " for (or against, for that matter !) any parti-
cular group of readers.-ED. L. 10. Pattengale, P. K., Smith, R. W., Gerber, P. Lancet, 1973, ii, 93. 11. See Lancet, Jan. 11, 1975, p. 92.
DIOGENES SYNDROME
SIR,-I should like to agree with some of the points made in this correspondence (March 1, p. 515, March 15, p. 627). Fire hazards to the patient and to neighbours can be very real, and can often ultimately tip the scales towards compulsory removal. One must also add the danger of gassing and explosions if the house has gas appliances. I cannot, however, agree that one must always respect the wish of the individual to neglect himself even unto death. I have seen some patients who did not do well in a geriatric unit or eventide home, but I have also seen many take on a new and happy life after admission to such units, particularly if the units are stimulating and well run. In Scotland, such cases are rarely handled by compulsory admission powers under the Mental Health (Scotland) Act 1960. More appropriate (and .effective) is Section 47 of the National Assistance Act 1948 (" unable to devote to themselves proper care and attention, and not receiving it from others... " &c.) or the National Assistance (Amendment) Act 1951. Non-conformity in itself is never a sure sign of psychiatric
disorder and whether or not one invokes
compulsory powers depend on as accurate a psychiatric assessment as possible. Personality inventories and psychometric I assessments, fear, have no place in helping the clinician to make up his mind in the patient’s home. Repeated visits are nearly always necessary before an accurate may well
be made. The decision on the correct course of action will always be difficult, but I feel that if the physician approaches each case with an open mind and weighs all the clinical, social, and domestic factors carefully, he will usually take the action which is in the patient’s best interests. assessment can
Department of Community Medicine, Ruchill Hospital, Glasgow G20 9NB.
H. MACANESPIE.
LEVAMISOLE
SIR,—Your editorial (Jan. 18, p. 151) calls for controlled clinical trials of levamisole, and at least two centres are already using it in the treatment of human malignancies.I,2 We wish to support the caution sounded by Dr Hopper and others,3 regarding the experimental evidence for tumour inhibition by levamisole. In our experience with levamisole (L-tetramisole), and with the racemic mixture (D-L-tetramisole) to which greater activity has been attributed,4the drug did not stimulate humoral or cellular immune responsiveness. We found no evidence of altered humoral antibody response to sheep erythrocytes injected in groups of mice receiving 1-25 mg. per kg. body-weight intraperitoneally of levamisole over various time schedules.- We did not observe either immunosuppression associated with drug therapy before antigen challenge, or immunostimulation associated with drug administration with or soon after antigen challenge, as reported by others.4 Similarly, we found no evidence of accelerated rejection of tail skin grafts in mice treated by similar schedules, which also failed to inhibit growth of a transplanted fat tumour. In this last experiment, rats immunised with irradiated Walker 256 tumour cells or inoculated with viable tumour received the drug (2-5 mg. In-vitro assays per kg. body-weight) intraperitoneally. showed no increase in serum-antibody potency or spleencell cytotoxicity at different times following tumour Webster, D. J. T., Hughes, L. E. Lancet, Feb. 15, 1975, p. 389. Amery, W. ibid. Hopper, D. G., Pimm, M. V., Baldwin, R. W. ibid. March 8, 1975, p. 574. 4. Renoux, G., Renoux, M. J. Immun. 1974, 113, 779. 1. 2. 3.
751
challenge. In contrast, retardation of the growth of a rat epithelioma has been achieved by other non-specific immunostimulants, such as killed Brucella abortus. If levamisole is an immunostimulant, we do not know what it might stimulate, and the possibility of exciting an undesirable kind of immunological reaction demands further investigation in animal models before opening the floodgates of necessarily less controllable clinical trials. Department of Pathology and Immunology, Monash University Medical School, Melbourne, Australia 3181.
G. R. FLANNERY
J. M. ROLLAND R. C. NAIRN.
PERSON-TO-PERSON TRANSMISSION OF ENTERIC BACTERIAL INFECTION SIR,-Dr Steere and his colleagues (Feb. 8, p. 319) have demonstrated person-to-person spread of salmonellosis in cases where predisposition due to reduced gastric activity or previous treatment with antibiotics was precluded. This faces the epidemiologist once more with the question why challenges with very low concentrations of enteric pathogenic bacteria can occasionally trigger disease in persons, whereas, when the same organisms are absorbed with food, doses well over 103 colony-forming units seem to be required.l Outbreaks of salmonellosis II-ó and shigellosis 6-10 transmitted in drinking-water that was certainly not grossly contaminated have presented similar
healthy
questions. Such questions have prompted us to carry out some investigations of the kinetics of the emptying of the stomach, using a 99mTc-colloid dispersion in water, its fate being studied with a gamma camera on line with a computer. This revealed that, in healthy individuals, small amounts of water (up to 50 ml.) taken between meals pass the pyloric area with very little delay. When such small volumes of liquid substrate contain enteric pathogens, these bacteria are hardly exposed to the bactericidal effect of gastric juice and hence reach the duodenum in virtually the same numbers as ingested. In this way very small numbers of cells may lead to disease. However, when the same bacteria are absorbed with solid food, intragastric-retention times are considerable. This results in a dramatic reduction of viable bacterial cells, at least in normoacidic subjects. In this instance very high numbers of cells have to be absorbed to allow at least a few to penetrate the duodenal and lower areas. The infecting dose of given enteropathogenic bacteria thus depends greatly on the carrier wherein the bacteria are contained, particularly water versus solid foods. Person-toperson spread of such pathogens might result from a saliva-borne infection secondary to transmission by the contaminated hand, similar to the triggering of enteric bacterial disease resulting from the consumption of relatively, small volumes of only very sparsely polluted drinking-water. Institute for Food of Animal
Origin, State University of Utrecht, Netherlands.
D. A. A. MOSSEL H. Y. OEI.
Armstrong, R. W., Fodor, T., Curling, G. T., Cohen, A. B., Morris, G. K., Martin, W. T., Feldman, J. Am. J. Epidem. 1970, 91, 300. 2. Greenberg, A. E., Ongerth, J. H. J. Am. Water Works Ass. 1966, 58, 1145. 3. Price, J., Carter, H. R. Publ. Hlth Rep., Wash. 1967, 82, 551. 4. Renteln, H. A., Himman, A. R. Am. J. Epidem. 1967, 86, 1. 5. Boring, J. R., Martin, W. T., Elliot, L. M. ibid. 1971, 93, 49. 6. Drachman, R. H., Payne, F. J., Jenkins, A. A. Am. J. Hyg. 1960, 72, 321. 7. Green, D. M., Scott, S. S., Mowat, D. A. E., Shearer, E. J. M., Thomson, J. M. J. Hyg., Camb. 1968, 66, 383. 8. Schiff, S., Landiak, E., Hinman, A. R., Altman, R. Morbid. Mortal. Wkly Rep. 1971, 20, 389. 9. Dorothy, L., Voelker, E. C., Bridson, K., Lindell, S., Hausler, W., Kosuri, M. R., Carr, F., Reeve, A. M. ibid. 1973, 22, 21. 10. Burr, J., Pearson, M., Quick, R., Saslaw, M. S., Craun, G. ibid. 1974, 23, 134.
BLOOD-LEAD LEVELS, BEHAVIOUR, AND INTELLIGENCE SIR,-Dr McCabe’s letter (Oct. 12, p. 896) criticising the Center for Disease Control’s report of psychological deficit in children appears to be an exception to an observation we and others have made. We have noted that reports and commentary on lead toxicity tend to sharply divide between those who are alarmed that " low level lead " exposure is accompanied by adverse health effects, particularly in neuropsychological performance, and those who argue that no case has been made for low-level lead exposure as a hazard. We could find no statement, report, or study by an industry-sponsored scientist, whether in-house grantee, or academic consultant, which frankly acknowledges that low-level exposure is hazardous. Those reports of toxicity due to low-level lead exposure, on the other hand, tend to from departments of public health, paediatrics, or environmental science. This observation appears well literature and by views expressed the recent supported by at three major meetings. 1-3 The association between nature of sponsorship and position on low-level lead toxicity appears challenged by Dr McCabe’s letter. Dr McCabe cited his affiliation as an academic department of paediatrics in Wisconsin, but argued that low-level-lead effects have not been demonstrated. We find, however, that his text was first published almost verbatim as an International Lead Zinc Research Organisation In-House Report, dated "July 16, 1974. In that report, the face sheet lists him as Edward McCabe, Pediatric Consultant, ILZRO (International Lead Zinc Research Organisation ". It is not our interest to question Dr McCabe’s intent. That the lead industry supports research on the health effects of its products, and hires medical consultants for opinions, seems only proper. That these consultants acknowledge industry support when entering industry-sponsored comment into the scientific arena, seems to us not only proper, but obligatory.
come
Harvard Medical School, and Children’s Hospital Medical
Center, Longwood Avenue, Boston, Massachusetts 02115,
300
U.S.A.
Case Western Reserve University University of Illinois, School of Public Health. Harvard Medical School.
Hospital for Sick Children, Toronto.
HERBERT L. NEEDLEMAN. SAMUEL EPSTEIN. BERTRAM CARNOW.
JOHN SCANLON. DAVID PARKINSON.
Industrial Union Department, AFL-CIO.
SHELDON SAMUELS.
Oil, Chemistry and Atomic Workers.
ANTHONY MAZZOCHI.
State University of New York, Downstate.
OLIVER DAVID.
1.
** *
We showed this letter to Dr McCabe, whose follows.-ED. L.
reply
letter signed by Dr Needleman and others scientific rebuttal to my letter, which contained
SIR,-The offers
no
Symposium on Health Effects of Lead. Congress of European Communities, Environmental Protection Agency, Amsterdam, 1972. 2. Low Level Lead Exposure. National Institute of Environmental Health Science, Environmental Protection Agency. Raleigh, North Carolina, 1973. Environmental Health Perspectives, no. 7, May, 1974. 3. International Symposium, Recent Advances in the Assessment of the Health Effects of Environmental Pollution, W.H.O., C.E.C., E.P.A., Paris, 1974. 1. International