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TOTAL FASTING FOR UP TO 249 DAYS
1082 groups, is two or three times higher in women under the age of 35 who have had more than four pregnancies than it is in any other group of women (including multiparous women in all the age-brackets over 35 years). No cases were detected among 654 nulliparous women below the age of 35. Young women of high parity are at great risk, and must be screened and rescreened at 5-year intervals if the incidence of cervical carcinoma is to be lowered in the community. Department of Obstetrics and Gynæcology, J. ELIZABETH MACGREGOR. University of Aberdeen.
MOUNTAIN SICKNESS
SIR,-I was interested to read Dr. Waterlow and Dr. Bunje’s observations on acute mountain sickness (Sept. 24, p. 655). Their reference to our work in the Himalayas1 suggests that we defined the time-course of early changes in respiratory control on acclimatisation. Actually the nature of the expediton precluded this since, as they point out, much acclimatisation takes place on the march out and during establishment of the highaltitude camps. We showed only that the decrease in carbondioxide " threshold " of response was complete by 5-7 days after moving from 14,000 to 19,000 feet. Kellogg,2 however, has shown that this change takes place rapidly. In 1 day after arrival at altitude half the change has taken place and it is com-
time-course of these three observations. It will be seen that the reduction in PC02 is very largely complete by the first observation, about 20 hours after arrival at altitude. The Pco2 fell from 49 to 42 mm. Hg in this time and thereafter fell slowly to 39 mm. Hg over the next 4 days, when it was the same as that of five subjects who had been at altitude for more than 6 months. This rapid lowering of Pco2 is probably due to the very rapid acidbase adjustment in the cerebrospinal fluid shown by Severinghaus et al. The urine pH did not rise as high as we expected, and the " alkaline tide " lasted only 2-3 days. The symptoms did not appear until 12-18 hours after arrival, reached a maximum at 36-48 hours, and did not clear until after 5 days. All values are means of the twenty subjects; there was of course quite a scatter, especially of symptoms severity. The results suggest that acid-base adjustment in the blood is largely complete before symptoms reach their maximum, and therefore probably is not the direct cause of acute mountain sickness. Christian Medical College and Hospital,
plete in about 8 days. From my observations in 1964 in collaboration with the Indian Armed Forces Medical Services, I agree with Dr. Water-
Post Box no. 3, Vellore 1, South India.
JAMES S. MILLEDGE.
TOTAL FASTING FOR UP TO 249 DAYS SiR,łHyperuricaemia accompanying the fasting state has been studied in rather more detail than is mentioned in the paper by Dr. Thomson and his colleagues (Nov. 5, p. 992). It is probably due to a direct inhibitory action of ketone bodies upon the renal tubular excretion of uric acid, since a fall in uric-acid clearance can be reproduced by infusion of P-hydro-
xybutyrate .6-77 Charing Cross Hospital, London W.C.2
J. T.
SCOTT.
ABO BLOOD-GROUPS AND SEX RATIO
SIR,-Allan8 suggested that the sex ratio varies with ABO blood-groups. In one series the order of sex ratios of newborn babies was shown to be B > 0 > A, but a larger series gave 0 > B. In all series combined, the conclusion was reached that the sex ratio of the 0 babies was very significantly higher than that of the A babies. I have examined a large sample of ABO blood-group data, consisting of nearly all children of school age and some adults in the 65 school areas on the island of Oahu, Hawaii, typed during 1942-43 by the Blood Bank of Hawaii for the Office of Civil Defense. - A total of 58,633 individuals with complete information on age, sex, and racial classification were included, representing 91-9% of the whole sample. They were of eight major races and their combinations. The Caucasian component was estimated to be about 24%. The numbers of individuals and proportions of males, both overall and adjusted by multiple regression within racial groups, for each ABO group were as follows:
low and Dr. Bunje that the usually accepted cause for acute mountain sickness-namely, that the symptoms are directly due to respiratory alkalosis-is inadequate, because we found that the time-course of the acid-base changes and of the symptoms did not coincide. Twenty army personnel were flown from sea-level to altitude in about 3 hours, and were taken from there to our station at 12,000 feet by road in another 2 hours. Symptoms of headache, anorexia (and nausea and vomiting), and sleeplessness were noted and scored. The urine pH was estimated by " universal indication strip " and mixed venous PC02 estimated by a rebreathing technique.3 The accompanying figure shows the 1.
Milledge, J. S. in Proceedings of the J. S. Haldane Centenary Symposium (edited by D. J. C. Cunningham and B. B. Lloyd); p. 397. Oxford,
2. 3.
Kellogg, R. H. ibid., p. 379. Campbell, E. J. M., Howell, I
1963. B I
Br med.
J. 1960, i, 458.
Based on Allan’s observations, three linear contrasts were set up-namely, (1) B >0, AB > A; (2) 0, AB > A, B; and (3) 0 > B, AB > A. I tested the null hypothesis of non-existence of ABO effects on sex ratios within racial groups in order to eliminate variations due to racial differences in gene frequencies. Similarly, age differences were simultaneously held constant by 4. 5. 6. 7.
8.
Severinghaus, J. W., Mitchell, R. A., Richardson, B. W., Singer, M. M. J. appl. Physiol. 1963, 18, 1155. Scott, J. T., McCallum, F. M., Holloway, V. P. Clin. Sci. 1964, 27, 209 Lecocq, F. R., McPhaull, J. J. Metabolism, 1965, 14, 186. Goldfinger, S., Klinenberg, J. R., Seegmiller, J. E. New Engl. J. Med. 1965. 272, 351. Allan, T. M. Br. med. J. 1959, i, 553.
MOUNTAIN SICKNESS
SIR,-I was interested to read Dr. Waterlow and Dr. Bunje’s observations on acute mountain sickness (Sept. 24, p. 655). Their reference to our work in the Himalayas1 suggests that we defined the time-course of early changes in respiratory control on acclimatisation. Actually the nature of the expediton precluded this since, as they point out, much acclimatisation takes place on the march out and during establishment of the highaltitude camps. We showed only that the decrease in carbondioxide " threshold " of response was complete by 5-7 days after moving from 14,000 to 19,000 feet. Kellogg,2 however, has shown that this change takes place rapidly. In 1 day after arrival at altitude half the change has taken place and it is com-
time-course of these three observations. It will be seen that the reduction in PC02 is very largely complete by the first observation, about 20 hours after arrival at altitude. The Pco2 fell from 49 to 42 mm. Hg in this time and thereafter fell slowly to 39 mm. Hg over the next 4 days, when it was the same as that of five subjects who had been at altitude for more than 6 months. This rapid lowering of Pco2 is probably due to the very rapid acidbase adjustment in the cerebrospinal fluid shown by Severinghaus et al. The urine pH did not rise as high as we expected, and the " alkaline tide " lasted only 2-3 days. The symptoms did not appear until 12-18 hours after arrival, reached a maximum at 36-48 hours, and did not clear until after 5 days. All values are means of the twenty subjects; there was of course quite a scatter, especially of symptoms severity. The results suggest that acid-base adjustment in the blood is largely complete before symptoms reach their maximum, and therefore probably is not the direct cause of acute mountain sickness. Christian Medical College and Hospital,
plete in about 8 days. From my observations in 1964 in collaboration with the Indian Armed Forces Medical Services, I agree with Dr. Water-
Post Box no. 3, Vellore 1, South India.
JAMES S. MILLEDGE.
TOTAL FASTING FOR UP TO 249 DAYS SiR,łHyperuricaemia accompanying the fasting state has been studied in rather more detail than is mentioned in the paper by Dr. Thomson and his colleagues (Nov. 5, p. 992). It is probably due to a direct inhibitory action of ketone bodies upon the renal tubular excretion of uric acid, since a fall in uric-acid clearance can be reproduced by infusion of P-hydro-
xybutyrate .6-77 Charing Cross Hospital, London W.C.2
J. T.
SCOTT.
ABO BLOOD-GROUPS AND SEX RATIO
SIR,-Allan8 suggested that the sex ratio varies with ABO blood-groups. In one series the order of sex ratios of newborn babies was shown to be B > 0 > A, but a larger series gave 0 > B. In all series combined, the conclusion was reached that the sex ratio of the 0 babies was very significantly higher than that of the A babies. I have examined a large sample of ABO blood-group data, consisting of nearly all children of school age and some adults in the 65 school areas on the island of Oahu, Hawaii, typed during 1942-43 by the Blood Bank of Hawaii for the Office of Civil Defense. - A total of 58,633 individuals with complete information on age, sex, and racial classification were included, representing 91-9% of the whole sample. They were of eight major races and their combinations. The Caucasian component was estimated to be about 24%. The numbers of individuals and proportions of males, both overall and adjusted by multiple regression within racial groups, for each ABO group were as follows:
low and Dr. Bunje that the usually accepted cause for acute mountain sickness-namely, that the symptoms are directly due to respiratory alkalosis-is inadequate, because we found that the time-course of the acid-base changes and of the symptoms did not coincide. Twenty army personnel were flown from sea-level to altitude in about 3 hours, and were taken from there to our station at 12,000 feet by road in another 2 hours. Symptoms of headache, anorexia (and nausea and vomiting), and sleeplessness were noted and scored. The urine pH was estimated by " universal indication strip " and mixed venous PC02 estimated by a rebreathing technique.3 The accompanying figure shows the 1.
Milledge, J. S. in Proceedings of the J. S. Haldane Centenary Symposium (edited by D. J. C. Cunningham and B. B. Lloyd); p. 397. Oxford,
2. 3.
Kellogg, R. H. ibid., p. 379. Campbell, E. J. M., Howell, I
1963. B I
Br med.
J. 1960, i, 458.
Based on Allan’s observations, three linear contrasts were set up-namely, (1) B >0, AB > A; (2) 0, AB > A, B; and (3) 0 > B, AB > A. I tested the null hypothesis of non-existence of ABO effects on sex ratios within racial groups in order to eliminate variations due to racial differences in gene frequencies. Similarly, age differences were simultaneously held constant by 4. 5. 6. 7.
8.
Severinghaus, J. W., Mitchell, R. A., Richardson, B. W., Singer, M. M. J. appl. Physiol. 1963, 18, 1155. Scott, J. T., McCallum, F. M., Holloway, V. P. Clin. Sci. 1964, 27, 209 Lecocq, F. R., McPhaull, J. J. Metabolism, 1965, 14, 186. Goldfinger, S., Klinenberg, J. R., Seegmiller, J. E. New Engl. J. Med. 1965. 272, 351. Allan, T. M. Br. med. J. 1959, i, 553.