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EFFECT OF SALBUTAMOL ON BLOOD-GAS TENSIONS IN ASTHMA
541
fairly well established (mestranol or ethinylaestradiol in doses ranging from 0-05 mg. to 0’1 mg.). My choice (in this country) would be ethinyloestradiol in a dose of 0-080.1 mg. There is a much wider range of choice with regard to the type and dose of progestogens, and the exact day in the cycle on which it is introduced. There are at present at least six readily available progestogens which can be used alone in very small doses: norgestrel is marginally effective in a daily dose of 0-075 mg., whereas lynestrenol and ethynodiol diacetate need to be given in daily doses of at least 0-25 mg. ; with norethisterone acetate the minimum effective daily dose is probably between 0-3 mg. and 0-5 mg.; with megestrol acetate and chlormadinone at least 0-5 mg. must be given (in this country 0-6-0-75 mg. would probably be safer). Clearly there is less margin for errors of omission and timing and more careful education of the patient is needed with the sequential and the low-dose-continuous regimens. Moreover the correct choice of dose vis-a-vis the ethnic group and its geographical placement is probably highly important. Bearing these points in mind it should be possible to bring the results with these two types of oral contraception nearly into line with those obtained with the combined tablet. MARGARET C. N. JACKSON Crediton, Devon. are
Medical Officer to the Exeter
Family Planning Association Clinic.
EFFECT OF SALBUTAMOL ON BLOOD-GAS TENSIONS IN ASTHMA Bass and his colleagues (Aug. 23, p. 438) SIR,-Dr. report a significant fall in arterial-blood oxygen tension measured from ear-lobe capillary blood in asthmatic children 30 minutes after the aerosol inhalation of salbutamol, although there was at that time a significant increase in forced expiratory volume (F.E.V. [time not specified]) and maximum voluntary ventilation (M.v.v.). This is at variance with our own findings in adults, where, although there was a significant improvement in both dynamic and static lung volumes, no fall in Pa02 occurred. 12 This we attributed to the fact that salbutamol, unlike isoprenaline, has little or no stimulant action on f3adrenergic receptors in the cardiovascular system3 and therefore does not increase cardiac output 4 or dilate pulmonary vasculature leading to intensification of ventilation/perfusion disturbances in the lung and worsening of hypoxaemia. There is, however, another factor which appears to determine the change in Pa02 after bronchodilator drugs. This is the extent to which the drug, in relieving airway obstruction, also reduces lung hyperinflation.5 We found Pa02 in asthma to correlate better with the forced vital capacity (F.v.c.) and the residual volume of the total lung capacity (R.v. %)-which are measures of lung hyperinflation-than with spirometric measurements of airway obstruction.2 6 F.E.v. and M.v.v., being time-dependent measurements, reflect airway obstruction rather than lung hyperinflation, and it will be interesting to know whether, in future work, Dr. Bass and his colleagues will be able to relate the changes in Pa02 after salbutamol to F.v.c. and R.V.% as well. Incidentally the dose is 200 {Lg. and not 200 mg. K. N. V. PALMER University Department of Medicine, M. L. DIAMENT. Aberdeen.
(Pao2)
1. 2. 3. 4. 5. 6.
Palmer, K. N. V., Diament, M. L. Br. med. J. 1969, i, 31. Palmer, K. N. V., Diament, M. L. Lancet, 1969, i, 591. Brittain, R. T., Farmer, J. B., Jack, D., Simpson, W. T. Nature, Lond. 1968, 219, 862. Kelman, G. R., Palmer, K. N. V., Cross, M. R. ibid. 1969, 221, 1251. Palmer, K. N. V., Diament, M. L. Lancet, 1968, i, 1372. Palmer, K. N. V., Diament, M. L. ibid. p. 318.
OOPHORECTOMY IN POSTMENOPAUSAL WOMEN WITH BREAST CANCER SIR,-In your annotation on this subject (Aug. 16, p. 366) you reached the conclusion that " the postmenopausal ovary produces no oestrogen and that its removal rarely, if ever, benefits the patient with breast cancer ". It would be a pity if early postmenopausal patients, especially those within a year of the menopause, were deprived-of a substantial chance of remission of their disease by readers who accept this conclusion. Patients within a year following the menopause rarely respond to other forms of hormonal therapy, and in an analysis of 501 patients with breast cancer treated by oophorectomy, the proportion of remissions in such cases was comparable to that found in premenopausal women.1-3 It is only in unselected series of postmenopausal patients, including those long past the menopause, that the remissionrate from castration falls below the 10% quoted in the annotation. In the absence of specific information concerning each individual’s ovarian activity after the menopause, I advise the surgical castration of patients with advanced breast cancer who had the menopause less than’a year ago, because the likelihood of remission is relatively high. Between one and five years following the menopause, I advise radiation castration (an effective but slower acting procedure) because the lesser likelihood of remission in this age-group may not
justify the surgical operation. Specific information is, however, available on the ovarian activity of the individual postmenopausal patient. Brown4 believes that ovarian cestrogen sources are suggested by high levels or by cyclical fluctuation in the excretion levels after the menopause. Castellanos et al. assume that ovarian oestrogen secretion is present after the menopause if oestrogen excretion is not suppressed by dexamethasone administration. Radiotherapy Department, St. Thomas’s Hospital, London S.E.1.
BASIL A. STOLL.
THE DISTENDING FORCE IN THE PRODUCTION OF COMMUNICATING SYRINGOMYELIA SIR,-In his paper on this subject (July 26,"p. 189), Mr. Williams uses the adjective " communicating to describe cases in which the syrinx communicates with the fourth ventricle. I have long maintained that all cases of true syringomyelia are due to such a communication and that the central canal becomes distended with ventricular fluid because of a partial obstruction of the outlets of the fourth ventricle. Neoplastic cysts in the central nervous system contain, not ventricular fluid, but rather a yellowish fluid of high protein content which is a transudate of blood-plasma. I cannot agree with Mr. Williams that changes in venous pressure, rather than the intracranial arterial pressure-wave, cause the ventricular fluid to distend and enlarge the syrinx. He points out that the pressure in the jugular veins will rise rapidly when they are obstructed and that such a rise in pressure is liable to occur in everyday living (a) by compression of the jugular veins from any cause, (b) by postural changes such as stooping or lying down, and (c) by forced expiration against a closed glottis. In reply to (a), I have never seen a positive Queckenstedt test in a patient with syringomyelia. This means that the intracranial and intra1. Barlow, J. J., Emerson, K., Saxena, B. N. New Engl. J. Med. 1969, 280, 633. 2. McDonald, J. Surg. Gynec. Obst. 1962, 115, 215. 3. Taylor, S. G. ibid. p. 443. 4. Brown, J. B. Personal communication. 5. Castellanos, H., Fairgrieve, J., O’Morchao, P. J., Moore, F. D. J. Am. med. Ass. 1963, 184, 295.
fairly well established (mestranol or ethinylaestradiol in doses ranging from 0-05 mg. to 0’1 mg.). My choice (in this country) would be ethinyloestradiol in a dose of 0-080.1 mg. There is a much wider range of choice with regard to the type and dose of progestogens, and the exact day in the cycle on which it is introduced. There are at present at least six readily available progestogens which can be used alone in very small doses: norgestrel is marginally effective in a daily dose of 0-075 mg., whereas lynestrenol and ethynodiol diacetate need to be given in daily doses of at least 0-25 mg. ; with norethisterone acetate the minimum effective daily dose is probably between 0-3 mg. and 0-5 mg.; with megestrol acetate and chlormadinone at least 0-5 mg. must be given (in this country 0-6-0-75 mg. would probably be safer). Clearly there is less margin for errors of omission and timing and more careful education of the patient is needed with the sequential and the low-dose-continuous regimens. Moreover the correct choice of dose vis-a-vis the ethnic group and its geographical placement is probably highly important. Bearing these points in mind it should be possible to bring the results with these two types of oral contraception nearly into line with those obtained with the combined tablet. MARGARET C. N. JACKSON Crediton, Devon. are
Medical Officer to the Exeter
Family Planning Association Clinic.
EFFECT OF SALBUTAMOL ON BLOOD-GAS TENSIONS IN ASTHMA Bass and his colleagues (Aug. 23, p. 438) SIR,-Dr. report a significant fall in arterial-blood oxygen tension measured from ear-lobe capillary blood in asthmatic children 30 minutes after the aerosol inhalation of salbutamol, although there was at that time a significant increase in forced expiratory volume (F.E.V. [time not specified]) and maximum voluntary ventilation (M.v.v.). This is at variance with our own findings in adults, where, although there was a significant improvement in both dynamic and static lung volumes, no fall in Pa02 occurred. 12 This we attributed to the fact that salbutamol, unlike isoprenaline, has little or no stimulant action on f3adrenergic receptors in the cardiovascular system3 and therefore does not increase cardiac output 4 or dilate pulmonary vasculature leading to intensification of ventilation/perfusion disturbances in the lung and worsening of hypoxaemia. There is, however, another factor which appears to determine the change in Pa02 after bronchodilator drugs. This is the extent to which the drug, in relieving airway obstruction, also reduces lung hyperinflation.5 We found Pa02 in asthma to correlate better with the forced vital capacity (F.v.c.) and the residual volume of the total lung capacity (R.v. %)-which are measures of lung hyperinflation-than with spirometric measurements of airway obstruction.2 6 F.E.v. and M.v.v., being time-dependent measurements, reflect airway obstruction rather than lung hyperinflation, and it will be interesting to know whether, in future work, Dr. Bass and his colleagues will be able to relate the changes in Pa02 after salbutamol to F.v.c. and R.V.% as well. Incidentally the dose is 200 {Lg. and not 200 mg. K. N. V. PALMER University Department of Medicine, M. L. DIAMENT. Aberdeen.
(Pao2)
1. 2. 3. 4. 5. 6.
Palmer, K. N. V., Diament, M. L. Br. med. J. 1969, i, 31. Palmer, K. N. V., Diament, M. L. Lancet, 1969, i, 591. Brittain, R. T., Farmer, J. B., Jack, D., Simpson, W. T. Nature, Lond. 1968, 219, 862. Kelman, G. R., Palmer, K. N. V., Cross, M. R. ibid. 1969, 221, 1251. Palmer, K. N. V., Diament, M. L. Lancet, 1968, i, 1372. Palmer, K. N. V., Diament, M. L. ibid. p. 318.
OOPHORECTOMY IN POSTMENOPAUSAL WOMEN WITH BREAST CANCER SIR,-In your annotation on this subject (Aug. 16, p. 366) you reached the conclusion that " the postmenopausal ovary produces no oestrogen and that its removal rarely, if ever, benefits the patient with breast cancer ". It would be a pity if early postmenopausal patients, especially those within a year of the menopause, were deprived-of a substantial chance of remission of their disease by readers who accept this conclusion. Patients within a year following the menopause rarely respond to other forms of hormonal therapy, and in an analysis of 501 patients with breast cancer treated by oophorectomy, the proportion of remissions in such cases was comparable to that found in premenopausal women.1-3 It is only in unselected series of postmenopausal patients, including those long past the menopause, that the remissionrate from castration falls below the 10% quoted in the annotation. In the absence of specific information concerning each individual’s ovarian activity after the menopause, I advise the surgical castration of patients with advanced breast cancer who had the menopause less than’a year ago, because the likelihood of remission is relatively high. Between one and five years following the menopause, I advise radiation castration (an effective but slower acting procedure) because the lesser likelihood of remission in this age-group may not
justify the surgical operation. Specific information is, however, available on the ovarian activity of the individual postmenopausal patient. Brown4 believes that ovarian cestrogen sources are suggested by high levels or by cyclical fluctuation in the excretion levels after the menopause. Castellanos et al. assume that ovarian oestrogen secretion is present after the menopause if oestrogen excretion is not suppressed by dexamethasone administration. Radiotherapy Department, St. Thomas’s Hospital, London S.E.1.
BASIL A. STOLL.
THE DISTENDING FORCE IN THE PRODUCTION OF COMMUNICATING SYRINGOMYELIA SIR,-In his paper on this subject (July 26,"p. 189), Mr. Williams uses the adjective " communicating to describe cases in which the syrinx communicates with the fourth ventricle. I have long maintained that all cases of true syringomyelia are due to such a communication and that the central canal becomes distended with ventricular fluid because of a partial obstruction of the outlets of the fourth ventricle. Neoplastic cysts in the central nervous system contain, not ventricular fluid, but rather a yellowish fluid of high protein content which is a transudate of blood-plasma. I cannot agree with Mr. Williams that changes in venous pressure, rather than the intracranial arterial pressure-wave, cause the ventricular fluid to distend and enlarge the syrinx. He points out that the pressure in the jugular veins will rise rapidly when they are obstructed and that such a rise in pressure is liable to occur in everyday living (a) by compression of the jugular veins from any cause, (b) by postural changes such as stooping or lying down, and (c) by forced expiration against a closed glottis. In reply to (a), I have never seen a positive Queckenstedt test in a patient with syringomyelia. This means that the intracranial and intra1. Barlow, J. J., Emerson, K., Saxena, B. N. New Engl. J. Med. 1969, 280, 633. 2. McDonald, J. Surg. Gynec. Obst. 1962, 115, 215. 3. Taylor, S. G. ibid. p. 443. 4. Brown, J. B. Personal communication. 5. Castellanos, H., Fairgrieve, J., O’Morchao, P. J., Moore, F. D. J. Am. med. Ass. 1963, 184, 295.