1291
Would not the cost of a national programme be better spent in the
provision of a more accessible service for patients with symptomatic breast disease by the appointment of surgeons, radiologists, and oncologists committed both to patient care and to the investigation of the biology and therapeutics of this all too common disease? Department of Surgery, University of Bristol, Bristol Royal Infirmary, Bristol BS2 8HW, UK
S. NICHOLSON R. FARNDON
J.
B*This letter has been shown to Dr Alexander and colleagues, replies follow.-ED. L. SIR,-The analysis presented in our report is standard for screening
whose
trial data and overcomes biases which otherwise arise-in particular, selection bias, which occurs if women who attended are formally compared with non-attenders, and lead time and length bias if survival comparisons (ie, use of case counts as denominators) are made.l,2 The pitfalls awaiting alternative analyses are not immediately apparent but are unanimously accepted by epidemiologists working in this area and also by most people involved in breast cancer screening. Unfortunately, this awareness of the correct methodology does not extend to the wider medical community so that, for example, claims for the efficiency of neuroblastoma screening are based on invalid analyses (eg, ref 3). We believe, therefore, that analysis of data from a well-designed breast cancer screening trial, in the way Mr Nicholson and Professor Famdon do in their table, is an unfortunate and retrograde step. The percentages in the final column are uninterpretable because of the effects of the three biases. The appropriate denominators are woman-years at risk. Nicholson and Famdon have sought to calculate these for the attenders by adding together the total number of screening visits given in table IV. Since many women did not return for later screening visits this is a gross underestimate. In our earlier letter (April 21, p 969) we give the total number of woman-years at risk for the ever-attenders and their breast cancer mortality rate, which is 30% lower than that in the controls and 36% lower than the never-attenders. Such comparisons are, of course, subject to selection bias but we cite them to emphasise that Nicholson and Famdon’s conclusions are false: our data in no way suggest "that the mortality for non-attenders does not differ from that of the attenders". Finally, we would emphasise that the Edinburgh study, correctly analysed and avoiding biases, found a 17 % reduction in mortality in the total study population when compared with the controls. This difference was not, however, statistically significant, and the 95% confidence interval includes reduction of up to 42% as well as being consistent with no reduction. Leukaemia Research Fund Centre, Department of Pathology, University of Leeds, Leeds LS2 9NG, UK; and University of Edinburgh Breast Cancer Screening Trial
F. E. ALEXANDER T. J. ANDERSON P. T. DONNAN R. J. PRESCOTT
PC, Hankey BF, Bundy BN Concepts and problems in the evaluation of screening programs. J Chronic Dis 1981; 34: 159-71. 2. Alexander FE. Statistical analysis of population screening. Med Lab Sci 1989; 46: 1. Prorok
255-67. 3. Sawada
T, Kidowaki T, Sakamoto I, et al. Neuroblastoma: detection and its prognosis. Cancer 1984; 53: 2731-35.
mass
screening for early
Intracranial pressure monitoring in fulminant hepatic failure and liver
transplantation SIR,-Liver transplantation
is
increasingly being
fulminant hepatic failure (FHF).1,2 Cerebral oedema is
done for a
frequent
fatal complication of FHF3 and significantly increases perioperative
mortality. Although intracranial pressure (ICP) is raised in models of acute hepatic failure,4 there are only isolated case reports on the use of ICP monitoring during liver transplantation. 5,6 We routinely use ICP monitors (subarachnoid screw) in patients with stage 4 encephalopathy due to FHF who are awaiting transplantation. In the past month, perioperative ICP has been
monitored
in 3 patients undergoing liver transplantation. Preoperative computed tomography (CT) scans confirmed cerebral swelling; maximum ICP was 30, 28, and 27 mm Hg, respectively. All responded to osmotherapy. Transcranial doppler analysis
showed normal flow velocities in all cerebral vessels studied. Intraoperative ICP increased acutely in all patients during reperfusion following liver transplantation, but returned to normal in the first 24 hours post transplantation. Improvement in hepatic function coincided with resolution of intracranial hypertension, encephalopathy, and CT evidence of cerebral swelling. The care of patients with FHF/grade 4 encephalopathy is greatly facilitated by ICP monitoring. Maximum ICP occurs during reperfusion of the transplanted liver.
Departments of Neurological Surgery and Surgery, University of Washington Medical Center, Seattle, WA 98195, USA
PETER D. LEROUX J. PAUL ELLIOTT JAMES D. PERKINS H. RICHARD WINN
S, Esquivel C, Gordon R. Liver transplantation for fulminant hepatic failure. 1985; 5: 325-28. 2. O’Grady J, Williams R. Management of acute liver failure. Schweiz Med Wochenschr 1986; 116: 541-44. 3. Ware A, D’Agnostino A, Combes B. Cerebral edema a major complication of massive hepatic necrosis. Gastroenterology 1971; 61: 877-84. 4. Hanid M, Mackenzie R, Jenner R, et al. Intracranial pressure in pigs with surgically induced acute liver failure. Gastroenterology 1979; 76: 123-31. 5. Brajtbord D, Parks R, Ramsay M, et al. Management of acute elevation of intracranial pressure during hepatic transplantation Anesthesiology 1989; 70: 139-41. 6. Potter D, Peachey T, Eason J, Ginsburg R, O’Grady J. Intracranial pressure 1. Iwatsuki
Sem Liver Dis
monitoring during orthotopic liver transplantation Transplant Proc 1989; 21: 3528.
for acute liver failure.
Calcitriol for osteoporosis SIR,-Your May 5 editorial on "new" treatments for osteoporosis includes one which is no longer new (oestrogen), one which you do not recommend (fluoride), and two which are in the early stages of assessment (calcitonin and bisphosphonates). Three
others, in regular use by us, are not mentioned—namely calcium,l nandrolone decanoate,2-4 and calcitriol, which corrects any malabsorption of calcium while lowering hydroxyproline excretion.5 There has been no significant loss of bone in our 99 cases treated for 149 patient-years at a dose of 0 25 µg calcitriol daily combined with a calcium supplement. Larger doses given without a calcium supplement may do more harm than good6 but our regimen is safe and effective. Division of Clinical Chemistry, Institute of Medical and Veterinary Science, Adelaide, South Australia 5000
ALLAN G. NEED HOWARD A. MORRIS B. E. CHRISTOPHER NORDIN
1. Nordin BEC, Heaney RB. Calcium supplementation of the diet: justified by present evidence. Br Med J 1990; 300: 1056-60. 2. Dequeker J, Geusens P. Anabolic steroids and osteoporosis. Acta Endocrinol 1985; 271: 45-52. 3. Johansen JS, Hassager C, Podenphant J, et al. Treatment of postmenopausal osteoporosis: is the anabolic steroid nandrolone decanoate a candidate? Bone Mineral 1989; 6: 77-86. 4. Need AG, Horowitz M, Walker CJ, Chatterton BE, Chapman IC, Nordin BEC.
Cross-over study of fat-correlated forearm mineral content during nandrolone decanoate therapy for osteoporosis. Bone 1989; 10: 3-6. 5. Need AG, Horowitz M, Philcox JC, Nordin BEC. 1,25-dihydroxycalciferol and calcium therapy in osteoporosis with calcium malabsorption. Mineral Electrolyte Metab 1985; 11: 35-40. 6. Ott SM, Chesnut CH. Calcitriol treatment is not effective m postmenopausal osteoporosis. Ann Intern Med 1989; 110: 267-74.
Unusual adverse reaction to
an
acaricide
with suspected scabies was SIR,-A 51-year-old healthy prescribed ’AscabioF (May and Baker), a scabicid solution, to apply all over the body twice daily for two consecutive days. At midday on the third day the patient became flushed and a swift downward spreading, burning facial erythema developed. He then had sudden headache, watering of the eyes, rhinorrhoea, sweating, and general malaise. On admission, he had a macular non-pruritic rash, mainly affecting the chest and back. The patient recovered spontaneously within a few hours. He had wine-laden breath and had consumed a moderate amount of red wine with a meal, suggesting a disulfiramlike effect of the drug. man
1292
Ascabiol includes tetraethylthiuram monosulphide which produces effects similar to those of disulphide compounds used to induce aversion to alcohol.l However, such a side-effect of acaricides has seldom been reported.2,3 It implies substantial percutaneous absorption of the drug, poorly documented so far but probably attributable to its liposolubility. Therefore, despite the apparent low frequency of this adverse reaction, patients on such treatment should be routinely advised to abstain from alcohol for at least 48 h. Dermatology Clinic, Hôpital St Jacques, 25030 Besancon Cedex, France 1.
Reynolds JEF, ed. Martindale: the Pharmaceutical Press, 1989: 1352.
TABLE II-CORRELATIONS BETWEEN LYMPHOSARCOMA OR PROSTATE CANCER INCIDENCE AND RADON, CALCULATED MINIMUM DOSE, AND ESTIMATED RADON-ASSOCIATED ALPHA-ACTIVITY AT 20BqjmJ
D. BLANC PH. DEPREZ extra
pharmacopoeia.
29th ed. London:
2. Gold S. A skinful of alcohol. Lancet 1966; ii: 1417. 3. Plouvier B, Lemoine X, De Coninck, P, et al. Effet antabuse lors de l’application d’un topique à base de monosulfirame. Nouv Presse Med 1982; 11: 3209.
Radon and prostate cancer SIR,-We have reported correlations (April 28, p 1008) between the international incidence of various cancers and radon levels in houses. In the light of the work by Gardner et all implicating occupational radiation exposure of fathers with cancer incidence in their children, we have applied the population-averaged radon values from the fourteen countries used previously to cancers of the reproductive system. The correlations are greater for male than for female organs (table I). In particular cancer of the prostate gland correlates strongly with radon (figure). TABLE I-CORRELATION COEFFICIENTS FOR CANCERS OF THE REPRODUCTIVE SYSTEM AND POPULATION-AVERAGED RADON EXPOSURE
Data from Cancer Incidence in FIve Continents Vol V except for * from vol III. t UK orily.
A no-threshold linear response model may be used to determine both the minimum alpha dose to the prostate and the minimum alpha activity, for an alpha-particle quality factor of 20. Despite the large errors in the analysis the predicted activity is much larger than would be expected from radon alone (table n). A possible interpretation is that high concentrations of radon daughters are present in the prostate. Although the alpha-activity in the prostate is unknown it is worth noting the similarity with a corresponding plot of lymphosarcoma
Cancer data from Cancer Incidents in FIve Continents vol V; countries with less than 10 cases omitted.
incidence and radon concentration. Lymphosarcoma correlates strongly with radon and the predicted alpha-activity to the critical cells is similar to that predicted for the prostate (table II). The average alpha-particle dose to the critical cells in lymphosarcoma induction is again unknown; however, work with natural long-lived alpha-emitters in tracheobronchial lymph nodes yields, by standard pathway calculations, 0- 19 mSv per year. Direct measurements in this laboratory3 indicated that activity was much greater, at 6-0 mSv annually. There seem to be very high doses from alpha-emitters in parts of the lymphatic system that are not predicted by model calculations-and long-lived alpha-emitting radionuclides may be present in the prostate in high concentrations also. If the mechanism implicated by Gardner et al is correct, naturally occurring alpha-emitters in the male reproductive organs could lead to the induction of natural childhood cancers. In radiation workers who receive internal contamination the nuclides may accumulate in the prostate. This would not be revealed by an external personal dose-meter. Workers at nuclear facilities do have high standardised mortality ratios for prostate cancer. 4-7 Accumulated radionuclides in the prostate could explain why a genetic effect is found in radiation workers but not in survivors of the Japanese atomic bombs, exposed to gamma and neutron radiation.8 H. H Wills Physics Laboratory, University of Bristol,
JONATHAN P. EATOUGH
Bristol BS8 1TL, UK
DENIS L. HENSHAW
1. Gardner MJ, Snee MP, Hall AJ, Powell CA, Downes S, Terrell JD. Results of case-control study of leukaemia and lymphoma among young people near Sellafield nuclear plant in West Cumbria. Br Med J 1990; 300: 423-34. 2. Committee on Medical Aspects of Radiation in the Environment (COMARE). Second report. London: HM Stationery Office, 1988. 3 Henshaw DL, Fews AP, Maharaj R, Shepherd L. Autopsy studies of the microdistribution of alpha-active nuclides in lung tissue Ann Occup Hyg 1988; 32: 1081-94. 4. Beral V, Inskip H, Fraser P, et al. Mortality of employees of the United Kingdom Atomic Energy Authonty, 1946-1979. Br Med J 1985; 29: 440-47. 5. Beral V, Fraser P, Carpenter L, Booth M, Brown A, Rose G. Mortality of employees at the Atomic Weapons Establishment Energy Authority, 1951-82. Br Med J 1988; 19: 757-70. 6. Smith PG, Douglas AJ. Mortality of workers at the Sellafield plant of British Nuclear Fuels. Br Med J 1986; 293: 845-52. 7. Checkoway H, Matthew RM, Shy CM, et al. Radiation, work experience, and cause specific mortality among workers at an energy research laboratory. Br J Ind Med 1985; 42: 525-33 8. Ishimaru T, Ishimaru M, Mikami M. Leukaemia incidence among individuals exposed m utero, children of atomic bomb survivors and their controls, Hiroshima and Nagasaki, 1945-79. Hiroshima: Radiation Effects Research Foundation, 1981.
CORRECTION
Incidence (per 100 000 per year).
Effects of coronary risk reduction on mortality.-In this letter by Dr N. Spritz (April 14, p 923) the end of the first paragraph should have read "... predict substantial decreases in deaths from all causes for men in whom cholesterol concentrations are lowered by 10 or 20%. This extrapolation is not supported by data from interventional studies in which cholesterol lowering has been achieved and in which a favourable effect on mortality has not been demonstrated". The last sentence of the third paragraph was omitted and should have read, "This, at least, indicates that the decision to include no time-lag between cholesterol lowering and diminished mortality is incorrect, and that at neither 5 nor 10 years after cholesterol lowering could improvement in overall mortality be predicted".
Would not the cost of a national programme be better spent in the
provision of a more accessible service for patients with symptomatic breast disease by the appointment of surgeons, radiologists, and oncologists committed both to patient care and to the investigation of the biology and therapeutics of this all too common disease? Department of Surgery, University of Bristol, Bristol Royal Infirmary, Bristol BS2 8HW, UK
S. NICHOLSON R. FARNDON
J.
B*This letter has been shown to Dr Alexander and colleagues, replies follow.-ED. L. SIR,-The analysis presented in our report is standard for screening
whose
trial data and overcomes biases which otherwise arise-in particular, selection bias, which occurs if women who attended are formally compared with non-attenders, and lead time and length bias if survival comparisons (ie, use of case counts as denominators) are made.l,2 The pitfalls awaiting alternative analyses are not immediately apparent but are unanimously accepted by epidemiologists working in this area and also by most people involved in breast cancer screening. Unfortunately, this awareness of the correct methodology does not extend to the wider medical community so that, for example, claims for the efficiency of neuroblastoma screening are based on invalid analyses (eg, ref 3). We believe, therefore, that analysis of data from a well-designed breast cancer screening trial, in the way Mr Nicholson and Professor Famdon do in their table, is an unfortunate and retrograde step. The percentages in the final column are uninterpretable because of the effects of the three biases. The appropriate denominators are woman-years at risk. Nicholson and Famdon have sought to calculate these for the attenders by adding together the total number of screening visits given in table IV. Since many women did not return for later screening visits this is a gross underestimate. In our earlier letter (April 21, p 969) we give the total number of woman-years at risk for the ever-attenders and their breast cancer mortality rate, which is 30% lower than that in the controls and 36% lower than the never-attenders. Such comparisons are, of course, subject to selection bias but we cite them to emphasise that Nicholson and Famdon’s conclusions are false: our data in no way suggest "that the mortality for non-attenders does not differ from that of the attenders". Finally, we would emphasise that the Edinburgh study, correctly analysed and avoiding biases, found a 17 % reduction in mortality in the total study population when compared with the controls. This difference was not, however, statistically significant, and the 95% confidence interval includes reduction of up to 42% as well as being consistent with no reduction. Leukaemia Research Fund Centre, Department of Pathology, University of Leeds, Leeds LS2 9NG, UK; and University of Edinburgh Breast Cancer Screening Trial
F. E. ALEXANDER T. J. ANDERSON P. T. DONNAN R. J. PRESCOTT
PC, Hankey BF, Bundy BN Concepts and problems in the evaluation of screening programs. J Chronic Dis 1981; 34: 159-71. 2. Alexander FE. Statistical analysis of population screening. Med Lab Sci 1989; 46: 1. Prorok
255-67. 3. Sawada
T, Kidowaki T, Sakamoto I, et al. Neuroblastoma: detection and its prognosis. Cancer 1984; 53: 2731-35.
mass
screening for early
Intracranial pressure monitoring in fulminant hepatic failure and liver
transplantation SIR,-Liver transplantation
is
increasingly being
fulminant hepatic failure (FHF).1,2 Cerebral oedema is
done for a
frequent
fatal complication of FHF3 and significantly increases perioperative
mortality. Although intracranial pressure (ICP) is raised in models of acute hepatic failure,4 there are only isolated case reports on the use of ICP monitoring during liver transplantation. 5,6 We routinely use ICP monitors (subarachnoid screw) in patients with stage 4 encephalopathy due to FHF who are awaiting transplantation. In the past month, perioperative ICP has been
monitored
in 3 patients undergoing liver transplantation. Preoperative computed tomography (CT) scans confirmed cerebral swelling; maximum ICP was 30, 28, and 27 mm Hg, respectively. All responded to osmotherapy. Transcranial doppler analysis
showed normal flow velocities in all cerebral vessels studied. Intraoperative ICP increased acutely in all patients during reperfusion following liver transplantation, but returned to normal in the first 24 hours post transplantation. Improvement in hepatic function coincided with resolution of intracranial hypertension, encephalopathy, and CT evidence of cerebral swelling. The care of patients with FHF/grade 4 encephalopathy is greatly facilitated by ICP monitoring. Maximum ICP occurs during reperfusion of the transplanted liver.
Departments of Neurological Surgery and Surgery, University of Washington Medical Center, Seattle, WA 98195, USA
PETER D. LEROUX J. PAUL ELLIOTT JAMES D. PERKINS H. RICHARD WINN
S, Esquivel C, Gordon R. Liver transplantation for fulminant hepatic failure. 1985; 5: 325-28. 2. O’Grady J, Williams R. Management of acute liver failure. Schweiz Med Wochenschr 1986; 116: 541-44. 3. Ware A, D’Agnostino A, Combes B. Cerebral edema a major complication of massive hepatic necrosis. Gastroenterology 1971; 61: 877-84. 4. Hanid M, Mackenzie R, Jenner R, et al. Intracranial pressure in pigs with surgically induced acute liver failure. Gastroenterology 1979; 76: 123-31. 5. Brajtbord D, Parks R, Ramsay M, et al. Management of acute elevation of intracranial pressure during hepatic transplantation Anesthesiology 1989; 70: 139-41. 6. Potter D, Peachey T, Eason J, Ginsburg R, O’Grady J. Intracranial pressure 1. Iwatsuki
Sem Liver Dis
monitoring during orthotopic liver transplantation Transplant Proc 1989; 21: 3528.
for acute liver failure.
Calcitriol for osteoporosis SIR,-Your May 5 editorial on "new" treatments for osteoporosis includes one which is no longer new (oestrogen), one which you do not recommend (fluoride), and two which are in the early stages of assessment (calcitonin and bisphosphonates). Three
others, in regular use by us, are not mentioned—namely calcium,l nandrolone decanoate,2-4 and calcitriol, which corrects any malabsorption of calcium while lowering hydroxyproline excretion.5 There has been no significant loss of bone in our 99 cases treated for 149 patient-years at a dose of 0 25 µg calcitriol daily combined with a calcium supplement. Larger doses given without a calcium supplement may do more harm than good6 but our regimen is safe and effective. Division of Clinical Chemistry, Institute of Medical and Veterinary Science, Adelaide, South Australia 5000
ALLAN G. NEED HOWARD A. MORRIS B. E. CHRISTOPHER NORDIN
1. Nordin BEC, Heaney RB. Calcium supplementation of the diet: justified by present evidence. Br Med J 1990; 300: 1056-60. 2. Dequeker J, Geusens P. Anabolic steroids and osteoporosis. Acta Endocrinol 1985; 271: 45-52. 3. Johansen JS, Hassager C, Podenphant J, et al. Treatment of postmenopausal osteoporosis: is the anabolic steroid nandrolone decanoate a candidate? Bone Mineral 1989; 6: 77-86. 4. Need AG, Horowitz M, Walker CJ, Chatterton BE, Chapman IC, Nordin BEC.
Cross-over study of fat-correlated forearm mineral content during nandrolone decanoate therapy for osteoporosis. Bone 1989; 10: 3-6. 5. Need AG, Horowitz M, Philcox JC, Nordin BEC. 1,25-dihydroxycalciferol and calcium therapy in osteoporosis with calcium malabsorption. Mineral Electrolyte Metab 1985; 11: 35-40. 6. Ott SM, Chesnut CH. Calcitriol treatment is not effective m postmenopausal osteoporosis. Ann Intern Med 1989; 110: 267-74.
Unusual adverse reaction to
an
acaricide
with suspected scabies was SIR,-A 51-year-old healthy prescribed ’AscabioF (May and Baker), a scabicid solution, to apply all over the body twice daily for two consecutive days. At midday on the third day the patient became flushed and a swift downward spreading, burning facial erythema developed. He then had sudden headache, watering of the eyes, rhinorrhoea, sweating, and general malaise. On admission, he had a macular non-pruritic rash, mainly affecting the chest and back. The patient recovered spontaneously within a few hours. He had wine-laden breath and had consumed a moderate amount of red wine with a meal, suggesting a disulfiramlike effect of the drug. man
1292
Ascabiol includes tetraethylthiuram monosulphide which produces effects similar to those of disulphide compounds used to induce aversion to alcohol.l However, such a side-effect of acaricides has seldom been reported.2,3 It implies substantial percutaneous absorption of the drug, poorly documented so far but probably attributable to its liposolubility. Therefore, despite the apparent low frequency of this adverse reaction, patients on such treatment should be routinely advised to abstain from alcohol for at least 48 h. Dermatology Clinic, Hôpital St Jacques, 25030 Besancon Cedex, France 1.
Reynolds JEF, ed. Martindale: the Pharmaceutical Press, 1989: 1352.
TABLE II-CORRELATIONS BETWEEN LYMPHOSARCOMA OR PROSTATE CANCER INCIDENCE AND RADON, CALCULATED MINIMUM DOSE, AND ESTIMATED RADON-ASSOCIATED ALPHA-ACTIVITY AT 20BqjmJ
D. BLANC PH. DEPREZ extra
pharmacopoeia.
29th ed. London:
2. Gold S. A skinful of alcohol. Lancet 1966; ii: 1417. 3. Plouvier B, Lemoine X, De Coninck, P, et al. Effet antabuse lors de l’application d’un topique à base de monosulfirame. Nouv Presse Med 1982; 11: 3209.
Radon and prostate cancer SIR,-We have reported correlations (April 28, p 1008) between the international incidence of various cancers and radon levels in houses. In the light of the work by Gardner et all implicating occupational radiation exposure of fathers with cancer incidence in their children, we have applied the population-averaged radon values from the fourteen countries used previously to cancers of the reproductive system. The correlations are greater for male than for female organs (table I). In particular cancer of the prostate gland correlates strongly with radon (figure). TABLE I-CORRELATION COEFFICIENTS FOR CANCERS OF THE REPRODUCTIVE SYSTEM AND POPULATION-AVERAGED RADON EXPOSURE
Data from Cancer Incidence in FIve Continents Vol V except for * from vol III. t UK orily.
A no-threshold linear response model may be used to determine both the minimum alpha dose to the prostate and the minimum alpha activity, for an alpha-particle quality factor of 20. Despite the large errors in the analysis the predicted activity is much larger than would be expected from radon alone (table n). A possible interpretation is that high concentrations of radon daughters are present in the prostate. Although the alpha-activity in the prostate is unknown it is worth noting the similarity with a corresponding plot of lymphosarcoma
Cancer data from Cancer Incidents in FIve Continents vol V; countries with less than 10 cases omitted.
incidence and radon concentration. Lymphosarcoma correlates strongly with radon and the predicted alpha-activity to the critical cells is similar to that predicted for the prostate (table II). The average alpha-particle dose to the critical cells in lymphosarcoma induction is again unknown; however, work with natural long-lived alpha-emitters in tracheobronchial lymph nodes yields, by standard pathway calculations, 0- 19 mSv per year. Direct measurements in this laboratory3 indicated that activity was much greater, at 6-0 mSv annually. There seem to be very high doses from alpha-emitters in parts of the lymphatic system that are not predicted by model calculations-and long-lived alpha-emitting radionuclides may be present in the prostate in high concentrations also. If the mechanism implicated by Gardner et al is correct, naturally occurring alpha-emitters in the male reproductive organs could lead to the induction of natural childhood cancers. In radiation workers who receive internal contamination the nuclides may accumulate in the prostate. This would not be revealed by an external personal dose-meter. Workers at nuclear facilities do have high standardised mortality ratios for prostate cancer. 4-7 Accumulated radionuclides in the prostate could explain why a genetic effect is found in radiation workers but not in survivors of the Japanese atomic bombs, exposed to gamma and neutron radiation.8 H. H Wills Physics Laboratory, University of Bristol,
JONATHAN P. EATOUGH
Bristol BS8 1TL, UK
DENIS L. HENSHAW
1. Gardner MJ, Snee MP, Hall AJ, Powell CA, Downes S, Terrell JD. Results of case-control study of leukaemia and lymphoma among young people near Sellafield nuclear plant in West Cumbria. Br Med J 1990; 300: 423-34. 2. Committee on Medical Aspects of Radiation in the Environment (COMARE). Second report. London: HM Stationery Office, 1988. 3 Henshaw DL, Fews AP, Maharaj R, Shepherd L. Autopsy studies of the microdistribution of alpha-active nuclides in lung tissue Ann Occup Hyg 1988; 32: 1081-94. 4. Beral V, Inskip H, Fraser P, et al. Mortality of employees of the United Kingdom Atomic Energy Authonty, 1946-1979. Br Med J 1985; 29: 440-47. 5. Beral V, Fraser P, Carpenter L, Booth M, Brown A, Rose G. Mortality of employees at the Atomic Weapons Establishment Energy Authority, 1951-82. Br Med J 1988; 19: 757-70. 6. Smith PG, Douglas AJ. Mortality of workers at the Sellafield plant of British Nuclear Fuels. Br Med J 1986; 293: 845-52. 7. Checkoway H, Matthew RM, Shy CM, et al. Radiation, work experience, and cause specific mortality among workers at an energy research laboratory. Br J Ind Med 1985; 42: 525-33 8. Ishimaru T, Ishimaru M, Mikami M. Leukaemia incidence among individuals exposed m utero, children of atomic bomb survivors and their controls, Hiroshima and Nagasaki, 1945-79. Hiroshima: Radiation Effects Research Foundation, 1981.
CORRECTION
Incidence (per 100 000 per year).
Effects of coronary risk reduction on mortality.-In this letter by Dr N. Spritz (April 14, p 923) the end of the first paragraph should have read "... predict substantial decreases in deaths from all causes for men in whom cholesterol concentrations are lowered by 10 or 20%. This extrapolation is not supported by data from interventional studies in which cholesterol lowering has been achieved and in which a favourable effect on mortality has not been demonstrated". The last sentence of the third paragraph was omitted and should have read, "This, at least, indicates that the decision to include no time-lag between cholesterol lowering and diminished mortality is incorrect, and that at neither 5 nor 10 years after cholesterol lowering could improvement in overall mortality be predicted".
