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TESTOSTERONE METABOLISM BY BREAST TUMOURS
714 shows a similar continuous increase from 62% at age 15-19 to 82% after age 50 and continuing after age 70. This is explained by a combination of two factors: first, the excess mortality among the most severely handicapped first admitted to hospital as children or young people; second, in the absence of other facilities, the need to admit to hospitals older less-handicapped people who have been cared for by their families until the parents become frail or die. These data are largely confirmed in the very recently published national census of hospital patients, published by the Department of Health and Social Security.
Thus the implementation of Cmnd. 4683 could indeed lower the average age of existing hospital residents. The task of providing effective programmes of care and education for the remaining younger and more dependent residents could be an exciting challenge, given the staff, resources, and skills to undertake it. Wessex Project on Mental Handicap, ALBERT KUSHLICK Wessex
Regional Hospital Board, Winchester.
adenocarcinoma implantation. The number of animals with pulmonary metastases at the time of death, as determined by the method of Wexler,3 was decreased by all forms of drug treatment, including aspirin. The results were:
Aspirin Heparin Warfarin *
90% 40% 30% 30% Fisher exact probability
-
0-05 0-025 0-025 test.
Aspirin may well be as effective in containing the spread of malignant disease as the more potent drugs, heparin and warfarin. This property may be important, even though aspirin is of little value in treating deep venous thrombosis. Department of Surgery, Cleveland Metropolitan General
Hospital,
ROGER BLUNDEN.
Probability.
Metastatic growth Saline control
Case Western Reserve University School of Medicine, Cleveland, Ohio 44109, U.S.A.
JAMES J. KOLENICH EDWARD G. MANSOUR ARTHUR FLYNN.
TESTOSTERONE METABOLISM BY BREAST TUMOURS
SIR,-We Mrs. Ash
can
(Sept.
confirm the finding of Dr. Jenkins and 9, p. 513) that human breast cancer can
convert testosterone to 5cx-dihydrotestosterone. However, we do not agree that this 5 rx-reductase activity is absent in
normal breast. In two of three specimens of histologically proven normal breast tissue obtained from breasts removed for carcinoma, we found that the conversion of testosterone to 5rx-dihydrotestosterone equalled that in the tumour itself. Similarly, conversion has been demonstrated in three specimens of normal breast tissue removed with a fibroadenoma. The hypothesis that conversions are higher in undifferentiated tumours is not supported by our finding that, in two of three fibroadenomas, the conversion of testosterone to 5
benign
tumours.
Department of Clinical Surgery, Royal Infirmary,
Edinburgh
EH3 9YW.
W. R. MILLER A. P. M. FORREST.
HÆMATOLOGICAL EFFECTS OF ASPIRIN
SiR,—The postoperative course of malignant conditions carries with it the possibility of venous thrombosis and, as was indicated lately (Sept. 2, p. 441), inhibition of platelet aggregation by aspirin is not the therapeutic answer. A problem which sometimes is more pressing is the prevention of the dissemination of viable tumour cells by the circulatory system. Metastases have been associated with thrombus formation1 as well as with platelet aggregation 2; a drug such as aspirin may be vital in treating this phase of surgically operative cancer. We have used aspirin in a
preliminary study as a means of controlling the vascular spread of potentially viable tumour cells. We compared aspirin with sodium heparin and sodium warfarin in preventing the formation of pulmonary Adenocarcinoma BW 10232 was inoculated 40 C57B1/6Jax mice and followed 2-5 weeks after cell injections. The mice were divided
metastases.
subcutaneously into
into four groups: saline control, 75 mg. per kg. aspirin, 3-0 mg. per kg. heparin, and 0-30 mg. per kg. warfarin, total daily dosage, and were begun on drugs at the time of 1.
2.
Coman, D. R. Cancer Res. 1961, 21, 1436. Gasic, G. J., Gasic, T. B., Stewart, C. C. Proc. U.S.A. 1968, 61, 46.
natn.
Acad.
Sci.,
ENZYME TREATMENT OF VITREOUS HÆMORRHAGE SiR,—Iwas most interested in the letter of Mr. Williamson and Dr. Forrester (Sept. 2, p. 488) on their use of urokinase for vitreous hsemorrhage in a 38-year-old diabetic. Although I think laser-beam photocoagulation is probably the best therapy for some ocular bleeds, may I comment on enzyme treatment of this condition ? I have used another enzyme, chymotrypsin, and am impressed by the way it helps clear the vision in some patients with massive vitreous haemorrhage in sickle-cell haemoglobin C (Hb/SC) disease in Accra. Commencing with an oral dosage of 2 tablets three times daily (300,000 units daily) two or three days after the massive bleed, one patient with recurrent haemorrhages noticed that his vision cleared much quicker than when chymotrypsin was not used. I have previously mentioned the complications and some aspects of the management of vitreous hxmorrhages in Hb/SC disease in Accra.44 There are at least two reasons why urokinase therapy should not be encouraged in the ophthalmopathy of sicklecell disease: (i) general anaesthesia was administered in order to introduce the urokinase into the eye, and, although experienced anxsthetists encountered no trouble anassthetising more than 500 consecutive sicklers for various surgical procedures in Accra,5 general anxsthesia should, if possible, be avoided in sickle-cell disease; (ii) urokinase (activator of plasminogen) which has helped to digest intraocular clots to clear vision can also impair " healing of lesions of the urinary pathways "and produce hasmaturia, which is another " hxmorrhagic " complication of sickle-cell haemoglobin C disease. In fact, epsilon-aminocaproic acid, which inhibits urokinase, has been used for hasmaturia in
hmmoglobinopathies.7 These considerations are not merely of theoretical interest, since Glasgow, where Mr. Williamson and Dr. Forrester work, has a large immigrant population with a relatively high incidence of hasmoglobinopathy. Figures from Accraunderline the importance of vitreous and renal haemorrhages in sickle-cell disease: of 605 consecutive Hb/SC patients seen at the Korle Bu Sickle-cell Clinic over a period of 6 years, 64 (10-6%) had vitreous haemorrhages, compared with 1 (0-2%) of 600 Hb/SS patients (?< 0-001). The frequency of hxmaturia was 15 (2-5%) in 603 con3. 4. 5. 6. 7. 8.
Wexler, H. J. natn. Cancer Inst. 1966, 36, 641. Konotey-Ahulu, F. I. D. Lancet, 1968, ii, 222. Oduro, K. A., Searle, J. Br. med. J. (in the press). Anderson, L. Acta chir. scand. 1962, 124, 355. Immergut, M. A., St. Evenson, T. J. Urol. 1965, 93, 110. Konotey-Ahulu, F. I. D. Unpublished.
Thus the implementation of Cmnd. 4683 could indeed lower the average age of existing hospital residents. The task of providing effective programmes of care and education for the remaining younger and more dependent residents could be an exciting challenge, given the staff, resources, and skills to undertake it. Wessex Project on Mental Handicap, ALBERT KUSHLICK Wessex
Regional Hospital Board, Winchester.
adenocarcinoma implantation. The number of animals with pulmonary metastases at the time of death, as determined by the method of Wexler,3 was decreased by all forms of drug treatment, including aspirin. The results were:
Aspirin Heparin Warfarin *
90% 40% 30% 30% Fisher exact probability
-
0-05 0-025 0-025 test.
Aspirin may well be as effective in containing the spread of malignant disease as the more potent drugs, heparin and warfarin. This property may be important, even though aspirin is of little value in treating deep venous thrombosis. Department of Surgery, Cleveland Metropolitan General
Hospital,
ROGER BLUNDEN.
Probability.
Metastatic growth Saline control
Case Western Reserve University School of Medicine, Cleveland, Ohio 44109, U.S.A.
JAMES J. KOLENICH EDWARD G. MANSOUR ARTHUR FLYNN.
TESTOSTERONE METABOLISM BY BREAST TUMOURS
SIR,-We Mrs. Ash
can
(Sept.
confirm the finding of Dr. Jenkins and 9, p. 513) that human breast cancer can
convert testosterone to 5cx-dihydrotestosterone. However, we do not agree that this 5 rx-reductase activity is absent in
normal breast. In two of three specimens of histologically proven normal breast tissue obtained from breasts removed for carcinoma, we found that the conversion of testosterone to 5rx-dihydrotestosterone equalled that in the tumour itself. Similarly, conversion has been demonstrated in three specimens of normal breast tissue removed with a fibroadenoma. The hypothesis that conversions are higher in undifferentiated tumours is not supported by our finding that, in two of three fibroadenomas, the conversion of testosterone to 5
benign
tumours.
Department of Clinical Surgery, Royal Infirmary,
Edinburgh
EH3 9YW.
W. R. MILLER A. P. M. FORREST.
HÆMATOLOGICAL EFFECTS OF ASPIRIN
SiR,—The postoperative course of malignant conditions carries with it the possibility of venous thrombosis and, as was indicated lately (Sept. 2, p. 441), inhibition of platelet aggregation by aspirin is not the therapeutic answer. A problem which sometimes is more pressing is the prevention of the dissemination of viable tumour cells by the circulatory system. Metastases have been associated with thrombus formation1 as well as with platelet aggregation 2; a drug such as aspirin may be vital in treating this phase of surgically operative cancer. We have used aspirin in a
preliminary study as a means of controlling the vascular spread of potentially viable tumour cells. We compared aspirin with sodium heparin and sodium warfarin in preventing the formation of pulmonary Adenocarcinoma BW 10232 was inoculated 40 C57B1/6Jax mice and followed 2-5 weeks after cell injections. The mice were divided
metastases.
subcutaneously into
into four groups: saline control, 75 mg. per kg. aspirin, 3-0 mg. per kg. heparin, and 0-30 mg. per kg. warfarin, total daily dosage, and were begun on drugs at the time of 1.
2.
Coman, D. R. Cancer Res. 1961, 21, 1436. Gasic, G. J., Gasic, T. B., Stewart, C. C. Proc. U.S.A. 1968, 61, 46.
natn.
Acad.
Sci.,
ENZYME TREATMENT OF VITREOUS HÆMORRHAGE SiR,—Iwas most interested in the letter of Mr. Williamson and Dr. Forrester (Sept. 2, p. 488) on their use of urokinase for vitreous hsemorrhage in a 38-year-old diabetic. Although I think laser-beam photocoagulation is probably the best therapy for some ocular bleeds, may I comment on enzyme treatment of this condition ? I have used another enzyme, chymotrypsin, and am impressed by the way it helps clear the vision in some patients with massive vitreous haemorrhage in sickle-cell haemoglobin C (Hb/SC) disease in Accra. Commencing with an oral dosage of 2 tablets three times daily (300,000 units daily) two or three days after the massive bleed, one patient with recurrent haemorrhages noticed that his vision cleared much quicker than when chymotrypsin was not used. I have previously mentioned the complications and some aspects of the management of vitreous hxmorrhages in Hb/SC disease in Accra.44 There are at least two reasons why urokinase therapy should not be encouraged in the ophthalmopathy of sicklecell disease: (i) general anaesthesia was administered in order to introduce the urokinase into the eye, and, although experienced anxsthetists encountered no trouble anassthetising more than 500 consecutive sicklers for various surgical procedures in Accra,5 general anxsthesia should, if possible, be avoided in sickle-cell disease; (ii) urokinase (activator of plasminogen) which has helped to digest intraocular clots to clear vision can also impair " healing of lesions of the urinary pathways "and produce hasmaturia, which is another " hxmorrhagic " complication of sickle-cell haemoglobin C disease. In fact, epsilon-aminocaproic acid, which inhibits urokinase, has been used for hasmaturia in
hmmoglobinopathies.7 These considerations are not merely of theoretical interest, since Glasgow, where Mr. Williamson and Dr. Forrester work, has a large immigrant population with a relatively high incidence of hasmoglobinopathy. Figures from Accraunderline the importance of vitreous and renal haemorrhages in sickle-cell disease: of 605 consecutive Hb/SC patients seen at the Korle Bu Sickle-cell Clinic over a period of 6 years, 64 (10-6%) had vitreous haemorrhages, compared with 1 (0-2%) of 600 Hb/SS patients (?< 0-001). The frequency of hxmaturia was 15 (2-5%) in 603 con3. 4. 5. 6. 7. 8.
Wexler, H. J. natn. Cancer Inst. 1966, 36, 641. Konotey-Ahulu, F. I. D. Lancet, 1968, ii, 222. Oduro, K. A., Searle, J. Br. med. J. (in the press). Anderson, L. Acta chir. scand. 1962, 124, 355. Immergut, M. A., St. Evenson, T. J. Urol. 1965, 93, 110. Konotey-Ahulu, F. I. D. Unpublished.