- Email: [email protected]
INDOMETHACIN IN BREAST CANCER
384 certain behavioural anomalies due
to
incapacity
to
acquire
basic knowledge because of verbal difficulties, and perhaps to the more fundamental disturbance of not grasping in four dimensions the actual experiences of comprehension and reasoning. If the results of our research corroborate our hypothesis, the non-verbal teaching of mathematics could be considered a therapy for behavioural anomalies in children; and it might be possible at a later stage to develop speech with mathematical symbols. Universities of Brussels and Mons.
J. CORDIER.
Vrije Universiteit Brussels, Belgium.
F. LOWENTHAL.*
Prostaglandins are widely distributed throughout the tissues and are thought to modify the specific effects of hormones locally at targets including the adrenal cortex, -thyroid, ovary, and mammary gland. Since the effect of agents such as indomethacin and aspirin is to inhibit the synthesis of prostaglandin in the tissuesit would not be surprising if they had an effect on the growth of hormonesensitive mammary cancer. I am engaged in the trial of a regimen, including indomethacin, in the treatment of a series of patients with advanced breast cancer. The animal studies noted above would suggest a trial of indomethacin in patients with hypercalcsemia complicating breast cancer and not responding to corticosteroid or phosphate therapy. Radiotherapy Department, St. Thomas’s Hospital, London SE1.
BASIL A. STOLL.
PREVENTION OF INFANTILE ATOPY
SIR,-Dr Taylor and his colleagues (July 21,
p. 111) are supplying laboratory evidence a brief period of allergen avoidance during a symptom-free vulnerable period might prevent much atopic disease ". I have for twenty-five years past so advised the atopic parents of newborns. They have been taught to keep the environmental allergen exposures as limited as possible and to maintain the simplest of diets during the first six months of the newborn’s life. As a result, significantly fewer of their offspring have clinical
be congratulated which suggests that "
to
B LYMPHOCYTES DURING CHILDHOOD
on
evidence of atopy. Department of Dermatology, Rush-Presbyterian St. Luke’s Medical Center, Chicago, Illinois, U.S.A.
SIR,-It has been shown that B cells carry a heavy density of immunoglobulins on their surface and can be identified by immunofluorescence staining.3 The number of lymphocytes bearing IgG, IgA, and IgM is important for the study of immunodeficiency states,4,5 neoplastic lymphocytes, 6-8 and irradiation-induced lymphopenia.9 Nevertheless, the number of B cells changes during child-
hood and differs from newborn babies to normal adults.10 It seems that the normal pattern has to be established during childhood.
S. J. KAPLAN.
INDOMETHACIN IN BREAST CANCER
SIR,-May I add a clinical comment to recent correspondence on the effect of indomethacin on experimental tumours? Tashjian et el.have reported that mouse fibrosarcoma can produce a bone-resorbing factor which, like prostaglandin E2, can be inhibited by indomethacin. Dr Powles’ group at the Chester Beatty Research Institute (July 14, p. 100) have reported that aspirin and indomethacin can inhibit the osteolytic effect of Walker 256 carcinoma metastases in rats, and prevent the tumour-induced hypercalcsemia. It is subsequently suggested by Dr LiVolsi (Aug. 4, p. 263) that the tumour-inhibiting effect of indomethacin may, in this
case
also, reflect inhibition of
prostaglandin E2. In the case of human mammary cancer with bone metastases, we are uncertain as to the mechanism of osteolysis and of the hypercalcaemia which occurs in about 15% of these cases. Serendipity has led to my observation that the prescription of indomethacin 100-150 mg. orally daily can markedly relieve the pain of bone metastases from breast cancer for 2 or even 3 months in some patients, although I have failed to show sclerosis or recalcification in such metastases unless radiation therapy is added. That the response is not merely a placebo effect is shown by the
following case-history: A woman aged 71 developed skeletal and soft-tissue metastases 7 years after mastectomy. The prescription of indomethacin 25 mg. four times a day relieved the pain of her bone metastases and was followed also by almost complete disappearance of a group of metastatic nodules, between 0-5 and 10 cm. in diameter, in the vicinity of the scar. Unfortunately, the patient could not tolerate treatment for longer than 2 months because of epigastric discomfort, and after a short regression the nodules were re-
activated. *
Present address: J. Van 1.
Rijswijcklaan, 106, Antwerp, Belgium. H., Voelkel, E. F., Levine, L., Goldhaber, B. J. exp. Med. 1972, 136, 1329.
Tashjian,
A.
Percentage of peripheral lymphocytes stained by immunofluorescence with anti IgG, IgA, and IgM sera.
Staining was carried out by the immunofluorescence method of Rabellino and Grey.3 We used monospecific immunosera, anti-IgG, anti-IgA, and anti-IgM (Hyland), whose specificity had been previously proved by immuno-
electrophoresis. The results are shown in the accompanying figure. All the neonates had in cord-blood IgA-bearing lymphpcytes, though scanty in number. Between 1 and 3 months all kinds of Ig-bearing cells decreased. We interpret this as an increase in their rate of transformation to plasma cells This without a corresponding increase in formation. would be another phenomenon of the postnatal adaptation
period. Departamento de Pediatria, Facultad de Medicina, Valladolid, Spain.
S. BLANCO A. BLANCO E. SANCHEZ VILLARES.
Flower, R. J., Vane, J. R. Nature, 1972, 240, 410. Rabellino, E., Grey, H. M. J. Immun. 1971, 106, 1418. Cooper, M., Lawton, A. R. Lancet, 1971, ii, 791. Siegal, F. P., Pernis, B., Kunkel, H. G. Eur. J. Immun. 1971, 1, 482. 6. Aisenberg, A. C., Bloch, K. J. New Engl. J. Med. 1972, 287, 272. 7. Papamichail, M., Holborow, E. J., Keit, H. J., Currey, H. L. F. Lancet, 1972, ii, 64. 8. Wilson, J. D., Nossal, G. J. ibid. 1971, ii, 788. 9. Stjernsward, J., Vanky, F., Jondal, M., Wigzell, H., Sealy, R. ibid. 1972, i, 1352. 10. Froland, S. S., Natvig, J. B. Clin. exp. Immun. 1972, 11, 495. 2. 3. 4. 5.
to
incapacity
to
acquire
basic knowledge because of verbal difficulties, and perhaps to the more fundamental disturbance of not grasping in four dimensions the actual experiences of comprehension and reasoning. If the results of our research corroborate our hypothesis, the non-verbal teaching of mathematics could be considered a therapy for behavioural anomalies in children; and it might be possible at a later stage to develop speech with mathematical symbols. Universities of Brussels and Mons.
J. CORDIER.
Vrije Universiteit Brussels, Belgium.
F. LOWENTHAL.*
Prostaglandins are widely distributed throughout the tissues and are thought to modify the specific effects of hormones locally at targets including the adrenal cortex, -thyroid, ovary, and mammary gland. Since the effect of agents such as indomethacin and aspirin is to inhibit the synthesis of prostaglandin in the tissuesit would not be surprising if they had an effect on the growth of hormonesensitive mammary cancer. I am engaged in the trial of a regimen, including indomethacin, in the treatment of a series of patients with advanced breast cancer. The animal studies noted above would suggest a trial of indomethacin in patients with hypercalcsemia complicating breast cancer and not responding to corticosteroid or phosphate therapy. Radiotherapy Department, St. Thomas’s Hospital, London SE1.
BASIL A. STOLL.
PREVENTION OF INFANTILE ATOPY
SIR,-Dr Taylor and his colleagues (July 21,
p. 111) are supplying laboratory evidence a brief period of allergen avoidance during a symptom-free vulnerable period might prevent much atopic disease ". I have for twenty-five years past so advised the atopic parents of newborns. They have been taught to keep the environmental allergen exposures as limited as possible and to maintain the simplest of diets during the first six months of the newborn’s life. As a result, significantly fewer of their offspring have clinical
be congratulated which suggests that "
to
B LYMPHOCYTES DURING CHILDHOOD
on
evidence of atopy. Department of Dermatology, Rush-Presbyterian St. Luke’s Medical Center, Chicago, Illinois, U.S.A.
SIR,-It has been shown that B cells carry a heavy density of immunoglobulins on their surface and can be identified by immunofluorescence staining.3 The number of lymphocytes bearing IgG, IgA, and IgM is important for the study of immunodeficiency states,4,5 neoplastic lymphocytes, 6-8 and irradiation-induced lymphopenia.9 Nevertheless, the number of B cells changes during child-
hood and differs from newborn babies to normal adults.10 It seems that the normal pattern has to be established during childhood.
S. J. KAPLAN.
INDOMETHACIN IN BREAST CANCER
SIR,-May I add a clinical comment to recent correspondence on the effect of indomethacin on experimental tumours? Tashjian et el.have reported that mouse fibrosarcoma can produce a bone-resorbing factor which, like prostaglandin E2, can be inhibited by indomethacin. Dr Powles’ group at the Chester Beatty Research Institute (July 14, p. 100) have reported that aspirin and indomethacin can inhibit the osteolytic effect of Walker 256 carcinoma metastases in rats, and prevent the tumour-induced hypercalcsemia. It is subsequently suggested by Dr LiVolsi (Aug. 4, p. 263) that the tumour-inhibiting effect of indomethacin may, in this
case
also, reflect inhibition of
prostaglandin E2. In the case of human mammary cancer with bone metastases, we are uncertain as to the mechanism of osteolysis and of the hypercalcaemia which occurs in about 15% of these cases. Serendipity has led to my observation that the prescription of indomethacin 100-150 mg. orally daily can markedly relieve the pain of bone metastases from breast cancer for 2 or even 3 months in some patients, although I have failed to show sclerosis or recalcification in such metastases unless radiation therapy is added. That the response is not merely a placebo effect is shown by the
following case-history: A woman aged 71 developed skeletal and soft-tissue metastases 7 years after mastectomy. The prescription of indomethacin 25 mg. four times a day relieved the pain of her bone metastases and was followed also by almost complete disappearance of a group of metastatic nodules, between 0-5 and 10 cm. in diameter, in the vicinity of the scar. Unfortunately, the patient could not tolerate treatment for longer than 2 months because of epigastric discomfort, and after a short regression the nodules were re-
activated. *
Present address: J. Van 1.
Rijswijcklaan, 106, Antwerp, Belgium. H., Voelkel, E. F., Levine, L., Goldhaber, B. J. exp. Med. 1972, 136, 1329.
Tashjian,
A.
Percentage of peripheral lymphocytes stained by immunofluorescence with anti IgG, IgA, and IgM sera.
Staining was carried out by the immunofluorescence method of Rabellino and Grey.3 We used monospecific immunosera, anti-IgG, anti-IgA, and anti-IgM (Hyland), whose specificity had been previously proved by immuno-
electrophoresis. The results are shown in the accompanying figure. All the neonates had in cord-blood IgA-bearing lymphpcytes, though scanty in number. Between 1 and 3 months all kinds of Ig-bearing cells decreased. We interpret this as an increase in their rate of transformation to plasma cells This without a corresponding increase in formation. would be another phenomenon of the postnatal adaptation
period. Departamento de Pediatria, Facultad de Medicina, Valladolid, Spain.
S. BLANCO A. BLANCO E. SANCHEZ VILLARES.
Flower, R. J., Vane, J. R. Nature, 1972, 240, 410. Rabellino, E., Grey, H. M. J. Immun. 1971, 106, 1418. Cooper, M., Lawton, A. R. Lancet, 1971, ii, 791. Siegal, F. P., Pernis, B., Kunkel, H. G. Eur. J. Immun. 1971, 1, 482. 6. Aisenberg, A. C., Bloch, K. J. New Engl. J. Med. 1972, 287, 272. 7. Papamichail, M., Holborow, E. J., Keit, H. J., Currey, H. L. F. Lancet, 1972, ii, 64. 8. Wilson, J. D., Nossal, G. J. ibid. 1971, ii, 788. 9. Stjernsward, J., Vanky, F., Jondal, M., Wigzell, H., Sealy, R. ibid. 1972, i, 1352. 10. Froland, S. S., Natvig, J. B. Clin. exp. Immun. 1972, 11, 495. 2. 3. 4. 5.