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RED BLOOD CELLS FOR CANCER PATIENTS
363
abnormal; they had observed them in tumour patients after radiotherapy and in individuals occupationally exposed to as
radioactive materials. We have found these variants in individuals who have never had any radiation therapy or exposure to radiation. Perhaps these variants make individuals prone to tumours and are not caused by radiation exposure, as claimed by Dooley et al.
Supported by Grant MCT-440-14. Medical Genetics Division, Department of Pediatrics, Meharry Medical College, Nashville, Tennessee 37208, U.S.A.
S. BARDHAN D. N. SINGH K. DAVIS
RED BLOOD CELLS FOR CANCER PATIENTS
SIR,-I am impressed by the results of the prospective study on the effect of pretransplantation transfusions of packed unwashed red and white blood cells on cadaver kidney graft survival reported by Dr Opelz and colleagues (June 6, p. 1223) and the implications that transfusions somehow create a state of immune tolerance. Since tumour antigens are in many ways similar to histocompatibility antigens and since the immune suppression created by the transfusions appeared to be rather non-selective for histocompatibility antigens, is it possible that patients with malignant tumours who receive transfusions of whole blood are suppressed to the point where the malignant tumour has a better chance to survive? Anaemia of various causes is commonly associated with malignant tumours. Perhaps such patients should be given only packed washed or frozen red blood cells (which are automatically washed) until some data are obtained on this problem. Division of Nephrology, Department of Medicine, Michael Reese Hospital, Chicago, Illinois 60616, U.S.A.
CLARENCE L.
GANTT
SURVIVAL AFTER A BLOOD ALCOHOL OF 1127
mg/dl
SIR,-A 59-year-old, 66 kg man was admitted after consumption of two and a half bottles of whisky over a few hours in a suicide attempt. There was no history of chronic alcoholism but the patient had had endogeneous depression in the preceeding weeks. He was deeply comatose, with a temperature of32°C. Laboratory tests revealed hypoxaemia and acidosis. His serum ethanol concentration on admission was 245 mmol/1 (1127 mg/dl), and 12 h later it was 123 mmol/1 (566 mg/dl). He required artificial ventilation and fluid therapy and vasopressors for the shock and acidosis. 6 h after admission he went into asystole; spontaneous cardiac rhythm returned after 4 min of conventional emergency therapy (including adrenaline and calcium). Over the ensuing days the patient’s course was complicated by a haemorrhagic pancreatitis with disseminated intravascular coagulation, pneumonia, and a bleeding gastric ulcer. Acute tubulointerstitial nephropathy developed with a plasma creatinine rising to 871 mol/1. In 20 days renal function returned to normal without haemodialysis. On discharge, 1 month after the acute intoxication, the patient showed no signs of physical or, according to his wife, intellectual damage. In acute ethanol intoxication a blood ethanol of 500 mg/dl carries only a 50% probability of survival,2 and death is usually caused by respiratory depression.3 To our knowledge the highest bloodethanol hitherto measured in a patient is 780 mg/dl.1 Medicine Department C,
University Hospital of Gentofte, DK-2900 Hellerup, Denmark
DAG BERILD HANS HASSELBALCH
1 Hammond KB, Rumack BH, Rodgerson DO. Blood ethanol: a report of
unusually high
levels m a living patient. JAMA 1973; 22: 64. 2 Lindblad B, Olsson R. Unusually high levels of blood alcohol? JAMA 1976; 236: 1600-02 3 Sellers EM, Kalant H. Alcohol intoxication and withdrawal. N Engl J Med 1976; 294: 757-62.
BREAST CANCER AND THE OESTROGEN WINDOW HYPOTHESIS
SIR,-The "oestrogen-window hypothesis"
on
the
aetiology
of
cancerl proposes that "normal oestrogen stimulation and inadequacy, characterised by diminished progesterone secretion, could explain the main epidemiological features of the aetiology of breast cancer" and that " unopposed oestrogen
breast luteal
stimulation is the most favourable state for tumour induction". On this hypothesis there are two main induction periods "the first prior to ovulatory menstrual cycles and the second during the perimenopausal period", and "Establishment of regular ovulatory cycles would be expected to considerably reduce susceptibility to tumour induction". Although the establishment of regular cycles does not guarantee an ovulatory cycle with normal luteal-phase progesterone secretion, women with regular cycles do have higher levels of luteal-phase progesterone than do women with irregular cycles.2The oestrogenwindow hypothesis would thus predict that the period from the onset of menstruation until the establishment of regular cycles will be longer for breast cancer patients. In our case-control study of breast cancer in women under age 333we recorded age at onset of menstruation (menarche) and age when regular menstruation was established. Contrary to the prediction of the oestrogen-window hypothesis the cases had established regular cycles significantly earlier than controls (table I). A woman with early menarche (age 12 or younger) and "immediate" establishment of regular cycles had an almost 4-fold increased risk of breast cancer when compared with a woman with late menarche and long duration of irregular cycles (table n). The paper of Tokunaga et al.4 on breast cancer risk in atomic bomb survivors from 1950-74 is also quoted in support of the oestrogen-window hypothesis. The claim is based on the apparent marked dependence of radiation breast cancer risk-on age at the time of the bomb (ATB). The summary of Tokunaga et al.4 reads: "Excess risk estimates ... for women aged 10-19, 20-29, 30-39 (ATB)... were 7-3, 4-2, 2.66 ... cases per million women per year per rad, respectively", so that the greatest risk is in the age group with inadequate corpus-luteum function. The summary fails to state, however, that these risk estimates were calculated ignoring all woman-years of exposure under age 30. This, of course, has no effect on women over age 30 ATB and progressively more and more effect on women exposed in the age group 20-29 and 10-19. When risk estimates are calculated for.all years between 1950-74 in all age groups the risks do not vary between these age groups (see
Tokunaga et al.4, fig. 1). The observation of Tokunaga et al. that radiation had no effect on breast cancer rates in women aged 40-49 ATB, although it apparently increased rates in women aged 50 + ATB, is intriguing. Many women aged 40-49 ATB will have been perimenopausal with inadequate corpus luteum function, so that this result is completely contrary to the oestrogen-window hypothesis. Two little known papers by Sawada5,6 may provide at least part of the key to these anomalous results. Sawada found that many radiation exposed women aged 40-49 ATB experienced a radiation induced menopause ATB. This induced ovarian failure will by itself have caused a lower breast cancer rate in exposed women.The fact that no effect of radiation was seen implies to us that extra breast cancers 1. Korenman SG. Oestrogen window hypothesis ofthe aetiology of breast cancer. Lancet 1980; i: 700-01. 2. Lee PA, Xenakis T, Winer J, et al. Puberty in girls: Correlation of serum levels of gondotropins, prolactin, androgens, estrogens, and progestins with physical changes. J Clin Endocrinol 1976; 43: 775-84. 3. Pike MC, Henderson BE, Casagrande JT, et al. Oral contraceptive use and early abortion as risk factors for breast cancer in young women. Br J Cancer 1981; 43: 72-76. 4. Tokunaga M, Norman JE, Asano M, et al. Malignant breast tumors among atomic bomb survivors, Hiroshima and Nagasaki, 1950-74. J Natn Cancer Inst 1979; 62: 1347-59. 5. Sawada H. Sexual function in female atomic bomb survivors 1949-57, Hiroshima. J Hiroshima Med Ass 1960; 13: 1158-70. 6. Sawada H. Sexual function in female atomic bomb survivors 1949-59, Hiroshima: Atomic Bomb Casualty Commission technical report 34-59. Hiroshima: ABCC, 1959. 7. MacMahon B, Cole P, Brown J Etiology of human breast cancer: a review. J Natn Cancer Inst 1973; 50: 21-42.
abnormal; they had observed them in tumour patients after radiotherapy and in individuals occupationally exposed to as
radioactive materials. We have found these variants in individuals who have never had any radiation therapy or exposure to radiation. Perhaps these variants make individuals prone to tumours and are not caused by radiation exposure, as claimed by Dooley et al.
Supported by Grant MCT-440-14. Medical Genetics Division, Department of Pediatrics, Meharry Medical College, Nashville, Tennessee 37208, U.S.A.
S. BARDHAN D. N. SINGH K. DAVIS
RED BLOOD CELLS FOR CANCER PATIENTS
SIR,-I am impressed by the results of the prospective study on the effect of pretransplantation transfusions of packed unwashed red and white blood cells on cadaver kidney graft survival reported by Dr Opelz and colleagues (June 6, p. 1223) and the implications that transfusions somehow create a state of immune tolerance. Since tumour antigens are in many ways similar to histocompatibility antigens and since the immune suppression created by the transfusions appeared to be rather non-selective for histocompatibility antigens, is it possible that patients with malignant tumours who receive transfusions of whole blood are suppressed to the point where the malignant tumour has a better chance to survive? Anaemia of various causes is commonly associated with malignant tumours. Perhaps such patients should be given only packed washed or frozen red blood cells (which are automatically washed) until some data are obtained on this problem. Division of Nephrology, Department of Medicine, Michael Reese Hospital, Chicago, Illinois 60616, U.S.A.
CLARENCE L.
GANTT
SURVIVAL AFTER A BLOOD ALCOHOL OF 1127
mg/dl
SIR,-A 59-year-old, 66 kg man was admitted after consumption of two and a half bottles of whisky over a few hours in a suicide attempt. There was no history of chronic alcoholism but the patient had had endogeneous depression in the preceeding weeks. He was deeply comatose, with a temperature of32°C. Laboratory tests revealed hypoxaemia and acidosis. His serum ethanol concentration on admission was 245 mmol/1 (1127 mg/dl), and 12 h later it was 123 mmol/1 (566 mg/dl). He required artificial ventilation and fluid therapy and vasopressors for the shock and acidosis. 6 h after admission he went into asystole; spontaneous cardiac rhythm returned after 4 min of conventional emergency therapy (including adrenaline and calcium). Over the ensuing days the patient’s course was complicated by a haemorrhagic pancreatitis with disseminated intravascular coagulation, pneumonia, and a bleeding gastric ulcer. Acute tubulointerstitial nephropathy developed with a plasma creatinine rising to 871 mol/1. In 20 days renal function returned to normal without haemodialysis. On discharge, 1 month after the acute intoxication, the patient showed no signs of physical or, according to his wife, intellectual damage. In acute ethanol intoxication a blood ethanol of 500 mg/dl carries only a 50% probability of survival,2 and death is usually caused by respiratory depression.3 To our knowledge the highest bloodethanol hitherto measured in a patient is 780 mg/dl.1 Medicine Department C,
University Hospital of Gentofte, DK-2900 Hellerup, Denmark
DAG BERILD HANS HASSELBALCH
1 Hammond KB, Rumack BH, Rodgerson DO. Blood ethanol: a report of
unusually high
levels m a living patient. JAMA 1973; 22: 64. 2 Lindblad B, Olsson R. Unusually high levels of blood alcohol? JAMA 1976; 236: 1600-02 3 Sellers EM, Kalant H. Alcohol intoxication and withdrawal. N Engl J Med 1976; 294: 757-62.
BREAST CANCER AND THE OESTROGEN WINDOW HYPOTHESIS
SIR,-The "oestrogen-window hypothesis"
on
the
aetiology
of
cancerl proposes that "normal oestrogen stimulation and inadequacy, characterised by diminished progesterone secretion, could explain the main epidemiological features of the aetiology of breast cancer" and that " unopposed oestrogen
breast luteal
stimulation is the most favourable state for tumour induction". On this hypothesis there are two main induction periods "the first prior to ovulatory menstrual cycles and the second during the perimenopausal period", and "Establishment of regular ovulatory cycles would be expected to considerably reduce susceptibility to tumour induction". Although the establishment of regular cycles does not guarantee an ovulatory cycle with normal luteal-phase progesterone secretion, women with regular cycles do have higher levels of luteal-phase progesterone than do women with irregular cycles.2The oestrogenwindow hypothesis would thus predict that the period from the onset of menstruation until the establishment of regular cycles will be longer for breast cancer patients. In our case-control study of breast cancer in women under age 333we recorded age at onset of menstruation (menarche) and age when regular menstruation was established. Contrary to the prediction of the oestrogen-window hypothesis the cases had established regular cycles significantly earlier than controls (table I). A woman with early menarche (age 12 or younger) and "immediate" establishment of regular cycles had an almost 4-fold increased risk of breast cancer when compared with a woman with late menarche and long duration of irregular cycles (table n). The paper of Tokunaga et al.4 on breast cancer risk in atomic bomb survivors from 1950-74 is also quoted in support of the oestrogen-window hypothesis. The claim is based on the apparent marked dependence of radiation breast cancer risk-on age at the time of the bomb (ATB). The summary of Tokunaga et al.4 reads: "Excess risk estimates ... for women aged 10-19, 20-29, 30-39 (ATB)... were 7-3, 4-2, 2.66 ... cases per million women per year per rad, respectively", so that the greatest risk is in the age group with inadequate corpus-luteum function. The summary fails to state, however, that these risk estimates were calculated ignoring all woman-years of exposure under age 30. This, of course, has no effect on women over age 30 ATB and progressively more and more effect on women exposed in the age group 20-29 and 10-19. When risk estimates are calculated for.all years between 1950-74 in all age groups the risks do not vary between these age groups (see
Tokunaga et al.4, fig. 1). The observation of Tokunaga et al. that radiation had no effect on breast cancer rates in women aged 40-49 ATB, although it apparently increased rates in women aged 50 + ATB, is intriguing. Many women aged 40-49 ATB will have been perimenopausal with inadequate corpus luteum function, so that this result is completely contrary to the oestrogen-window hypothesis. Two little known papers by Sawada5,6 may provide at least part of the key to these anomalous results. Sawada found that many radiation exposed women aged 40-49 ATB experienced a radiation induced menopause ATB. This induced ovarian failure will by itself have caused a lower breast cancer rate in exposed women.The fact that no effect of radiation was seen implies to us that extra breast cancers 1. Korenman SG. Oestrogen window hypothesis ofthe aetiology of breast cancer. Lancet 1980; i: 700-01. 2. Lee PA, Xenakis T, Winer J, et al. Puberty in girls: Correlation of serum levels of gondotropins, prolactin, androgens, estrogens, and progestins with physical changes. J Clin Endocrinol 1976; 43: 775-84. 3. Pike MC, Henderson BE, Casagrande JT, et al. Oral contraceptive use and early abortion as risk factors for breast cancer in young women. Br J Cancer 1981; 43: 72-76. 4. Tokunaga M, Norman JE, Asano M, et al. Malignant breast tumors among atomic bomb survivors, Hiroshima and Nagasaki, 1950-74. J Natn Cancer Inst 1979; 62: 1347-59. 5. Sawada H. Sexual function in female atomic bomb survivors 1949-57, Hiroshima. J Hiroshima Med Ass 1960; 13: 1158-70. 6. Sawada H. Sexual function in female atomic bomb survivors 1949-59, Hiroshima: Atomic Bomb Casualty Commission technical report 34-59. Hiroshima: ABCC, 1959. 7. MacMahon B, Cole P, Brown J Etiology of human breast cancer: a review. J Natn Cancer Inst 1973; 50: 21-42.