- Email: [email protected]
CANCER RESEARCH CAMPAIGN
139
of men had no formal mental illness. LODGE PATCH, 24 after a psychiatric survey of a lodging-house sample in London, reported that half the group had abnormal personalities manifest in various defined ways. Characteristically, their sexual attitudes were such as to handicap them in establishing a stable relationship and thereby a home. Nevertheless, many gave histories of successful and often long careers in the Services. Their social incapacities or failure became apparent only in ordinary civilian life. decade during which the role of the mental hospital has changed and much progress has been made towards extramural care, ignorance still often prevails about many of society’s problems, such as those of the homeless. At the same time, patterns of service are now taking shape which may not change for many years. What are the special yet attainable needs for this large group of men, who rely heavily on social security, who often serve short sentences in prison, whose work record is grotesquely erratic ? Is it beyond our ingenuity to devise for them a framework within which they can function as happily and effectively as they often did in the Forces ? Those with chronic illnesses are exceptionally common in this population; and those with psychiatric disabilities seem to evade continued treatment, no doubt in part because of their elusiveness outside hospital. With more rapid discharge from hospital, the problem may be increasing. BERRY and ORWIN,25 reviewing admissions to the psychiatric hospitals serving Birmingham, found that between 1961 and 1965 those of no fixed abode had risen from 8-3% to 13-6%. LODGE PATCH 24 reported that, of his sample of 123 men, 18 had gross schizophrenia, and all 18 had been in hospital but only 3 were having any form of outpatient treatment. Such men are commonly unacceptable in voluntary hostels, as Iscs 26has pointed out, yet they need some definite help if they are not to drift back into prison or hospital. The time has come for a nationwide policy on hostels. At present too much of a burden is placed on the services of the independent voluntary agencies, such as the Salvation Army, without sufficient public support or money. Nor has community care by local authorities developed sufficiently or uniformly enough to plug the gap. With more staff, better exchange of information between hostel and hospital, training programmes, special provision for particular groups of men, and more research, much might be done to bring stability and more regular employment to homeless single men, and incidentally to confer some human dignity on an often degraded section of the community. All this needs planning on an informed national basis, and a critical opportunity may be After
a
passing. 24. 25. 26.
Lodge Patch, I. C. Proc. R. Soc. Med. 1970, 63, 437. Berry, C., Orwin, A. Br. J. Psychiat. 1966, 112, 1019. Isaacs, A. D. Public lecture, Institute of Psychiatry, London, May 20, 1970.
CANCER RESEARCH CAMPAIGN
ONE outcome of the changes in the affairs of the Cancer Research Campaign (until lately the British Empire Cancer Campaign for Research) is to be a new format for its annual report: the fat grey volume for 1969 just published1 is to be the last of its kind. This change will be welcome if the new style enables the reader to find more easily the important and significant advances by the institutions and individuals supported by the Campaign and if contributions can be set in a meaningful context of worldwide cancer research. In an area as complex as cancer research, there is always a need for two quite different types of individual: the one who looks for basic truths in specially developed model systems designed to overcome the tiresome fact of biological variation; and the other, the tireless observer, who is content to observe and record the seemingly infinite number of different patterns of web which Nature weaves as a corollary of the principle of natural selection. The two are in complementary, and advance knowledge depends At present, on a proper balance between the two. studies in molecular biology in relation to cancer suffer because of an excess of the first kind of worker.
survival based
on
Tyne, R. J. Scothorne2 reports that histoincompatible intramuscular thyroid grafts were rejected by mice bearing skin-grafts from the same donor, but survived in mice without skingrafts. Survival in the second case is likely to be due to failure of the afferent limb of the homograft reaction. Similar experiments indicated that intratesticular grafts survived even in mice bearing immunising skingrafts, suggesting a failure in the efferent limb, probably dependent on the paucity of lymphatic From Newcastle upon
vessels in the testis. The absence of immunoblasts in the lymphatic vessels draining the pregnant uterus is consistent with the hypothesis that the lumen of uterus is an immunologically privileged site. C. Rudenstam and others3 find that the risk of metastasis is increased when the thoracic duct of a rat bearing a benzpyrene-induced sarcoma in the hind leg is drained for a period of six days before amputation of the affected limb. They claim that the responsible of the thoracic lymph is in the y-globulin component fraction. In the past, inhibition of tumour growth has been the criterion in most screening tests of potential chemotherapeutic agents for cancer. Several attempts have been made to develop screening systems in which the ability of a test substance to inhibit metastasis could be detected. Progress along these lines is now reported 4 in experiments with two transplantable hamster lymphomas, of which one metastasises and the other does not. In the case of the metastasising lymphoma, the frequency of metastasis increased and decreased pari passu with the effects of chemical treatment on the primary tumour graft. Treatment with 5-aziridino-2, 1. 47th Annual Report of the British Empire Cancer Campaign for Research covering the year 1969. The Campaign’s offices are at 2 Carlton House Terrace, London S.W.1. 2. Scothorne, R. J. Rep. Br. Emp. Cancer Campn, 1969, 47, 298. 3. Rudenstam, C., Proctor, J., Alexander, P. ibid. p. 84. 4. Carter, R. L., Mitchley, B. C. V. ibid. p. 52.
140
4-dinitrobenzamide (CB 1954) or with actinomycin D at certain dose levels, however, actually favoured metastasis by the non-metastasising lymphoma. J. Marchant5 reports that the administration of antilymphocyte serum at the time of injection of methylcholanthrene into mice reduced the incidence of sarcoma at the site of injection of methylcholanthrene. This result is the opposite to that expected in the light of the enhancement of carcinogenic response by thymectomy and to that observed by R. K. Gershon and R. L. Carter 6-namely, increased growth at the subcutaneous inoculation site and stimulation of metastasis when antilymphocyte serum is given to hamsters bearing grafts of a normally non-metastasising
tumorigenic effects of a carcinogen of the polycyclic aromatic hydrocarbon type. Basic inquiries of these kinds will, it is to be hoped, provide much-needed
lymphoma.
tains
Other observations by Marchant7 also stand out the trend. It has become fashionable to discover un-host-like antigens in primary neoplasms. Marchant’s failure to discover immunogenic properties in spontaneous reticular or mammary tumours of putatively non-viral origin in mice emphasises that the existence of exploitable immunological differences between host and tumour should not be
against
presumed. I. A. Evans and her colleagues8 in Bangor, from their work on the carcinogenecity of bracken, believe the toxic principle has an empirical formula of C7Hs04, with a carboxylic-acid group in its molecule, but no benzene ring. Dominant lethal mutations, malignant lymphoma, and neoplasms of lung, liver, and gastrointestinal tract have been induced by giving this substance to mice. Furthermore, there is evidence of transfer of a carcinogenic principle from mothers to their progeny via the placenta and/or the milk. The development of a method for detecting the active compound chromatographically has made it possible to look for it in cow’s milk and in foods consumed in Japan, where a very high risk of cancer of the stomach may be related to the consumption of bracken. Brackens of varieties consumed in Japan have been shown to induce cancers in rats, and the carcinogenic principle has been demonstrated by chromatography in the canned product’Warabi ’. There is an increasing awareness of the possible influence of gut flora and of the enzymes they produce on nutrition and on the activity of drugs and in relation to carcinogenecity.9The role of gut flora in converting a non-carcinogenic precursor in cycad meal to an active carcinogen is well known.1o New findings in the United States 11 point to differences between germfree and conventionally maintained rats in the way they metabolise the carcinogen, N-hydroxy-N-2-fluorenylacetamide. Work in this country 12 has shown that germ-free status may, under certain circumstances, dramatically reduce the susceptibility of mice to the Marchant, J. ibid. p. 280. Gershon, R. K., Carter, R. L. Nature, Lond. 1970, 226, 368. Marchant, J. Rep. Br. Emp. Cancer Campn, 1969, 47, 279. Evans, I. A., Barber, G. D., Jones, R. S., Leach, H. ibid. p. 446. 9. Lancet, 1970, i, 552. 10. Laqueur, G. L., McDaniel, E. G., Matsumoto, H. J. natn. Cancer Inst. 1967, 39, 355. 11. Grantham, P. H., Horton, R. E., Weisburger, E. K., Weisburger, J. H. Biochem. Pharmacol. 1970, 19, 163. 12. Grant, G. A., Roe, F. J. C. Rep. Br. Emp. Cancer Campn, 1969, 47, 35. 5. 6. 7. 8.
clues
to
the causation of
gastrointestinal
cancers.
THE CAROTID BODY THE carotid body, that small lobulated structure at the fork of the common carotid artery, consists of groups of cells, surrounded by cellular fibrous tissue, with a rich supply of blood-vessels and nerves. It contwo types of parenchymal cell : the type-l or chief and the slightly less numerous type-li or sustentacell, cular cell. The chief cells show some variation in depth of staining of their cytoplasm and have been subdivided into light and dark cells. Sustentacular cells have long processes which envelop the surface of the chief cells and separate them from the adjacent capillaries.1 Bloodflow through the carotid body, per unit of tissue, is greater than in any other organ of the body, being about forty times that of the heart and four times that of the thyroid.2
Debate continues about the origin and function of the carotid body.3 It is a chemoreceptor organ, and one main physiological function is to respond to a low blood-oxygen tension. Apart from the rare carotidbody tumour, little is known of pathological changes in the organ. Chemical analysis has demonstrated the presence of catecholamines and noradrenaline in the carotid body and its tumourS,4and the chief cells, both normal and neoplastic, have been shown by studies of ultrastructure to contain abundant granules of catecholamine type.5 6
noted that the carotid bodies were significantly larger in people living at high altitudes than in those living at sea level, though there were no differences in histological characteristics. As this observation suggested that sustained hypoxia resulted in hyperplasia, Heath et al. examined the carotid bodies in patients dying of respiratory disease. They studied the carotid bodies in 40 successive necropsies-an unselected group that included 9 cases of emphysema, 2 of cor pulmonale, and 1 of the pickwickian syndrome. The carotid bodies were carefully dissected out and weighed, and a detailed histological examination and differential cell-counts were performed on 21 specimens. In every case the heart was dissected8 to obtain the weights of the right and left ventricles. The weights of the two carotid bodies together ranged from 4-7 mg. to 84-8 mg. with a mean combined weight of 24-2 mg. There was no correlation between the patients’ age and carotid-body weight. In the patients with emphysema the mean weight of Arias-Stella
1. 2. 3. 4. 5. 6. 7. 8.
Grimley, P. M., Glenner, G. G. Circulation, 1968, 37, 648. Bell, G. H., Davidson, J. N., Scarborough, H. Textbook of Physiology and Biochemistry. London, 1968. Karnauchow, P. N. Can. med. Ass. J. 1965, 92, 1298. Pryse-Davies, J., Dawson, I. M. P., Westbury, G. Cancer, N.Y. 1964, 17, 185. Grimley, P. M., Glenner, G. G. ibid. 1967, 20, 1473. Arias-Stella, J. Am. J. Path. 1969, 55, 82a. Heath, D., Edwards, C., Harris, P. Thorax, 1970, 25, 129. Fulton, R. M., Hutchinson, E. C., Jones, A. M. Br. Heart J. 1952, 14, 413.
of men had no formal mental illness. LODGE PATCH, 24 after a psychiatric survey of a lodging-house sample in London, reported that half the group had abnormal personalities manifest in various defined ways. Characteristically, their sexual attitudes were such as to handicap them in establishing a stable relationship and thereby a home. Nevertheless, many gave histories of successful and often long careers in the Services. Their social incapacities or failure became apparent only in ordinary civilian life. decade during which the role of the mental hospital has changed and much progress has been made towards extramural care, ignorance still often prevails about many of society’s problems, such as those of the homeless. At the same time, patterns of service are now taking shape which may not change for many years. What are the special yet attainable needs for this large group of men, who rely heavily on social security, who often serve short sentences in prison, whose work record is grotesquely erratic ? Is it beyond our ingenuity to devise for them a framework within which they can function as happily and effectively as they often did in the Forces ? Those with chronic illnesses are exceptionally common in this population; and those with psychiatric disabilities seem to evade continued treatment, no doubt in part because of their elusiveness outside hospital. With more rapid discharge from hospital, the problem may be increasing. BERRY and ORWIN,25 reviewing admissions to the psychiatric hospitals serving Birmingham, found that between 1961 and 1965 those of no fixed abode had risen from 8-3% to 13-6%. LODGE PATCH 24 reported that, of his sample of 123 men, 18 had gross schizophrenia, and all 18 had been in hospital but only 3 were having any form of outpatient treatment. Such men are commonly unacceptable in voluntary hostels, as Iscs 26has pointed out, yet they need some definite help if they are not to drift back into prison or hospital. The time has come for a nationwide policy on hostels. At present too much of a burden is placed on the services of the independent voluntary agencies, such as the Salvation Army, without sufficient public support or money. Nor has community care by local authorities developed sufficiently or uniformly enough to plug the gap. With more staff, better exchange of information between hostel and hospital, training programmes, special provision for particular groups of men, and more research, much might be done to bring stability and more regular employment to homeless single men, and incidentally to confer some human dignity on an often degraded section of the community. All this needs planning on an informed national basis, and a critical opportunity may be After
a
passing. 24. 25. 26.
Lodge Patch, I. C. Proc. R. Soc. Med. 1970, 63, 437. Berry, C., Orwin, A. Br. J. Psychiat. 1966, 112, 1019. Isaacs, A. D. Public lecture, Institute of Psychiatry, London, May 20, 1970.
CANCER RESEARCH CAMPAIGN
ONE outcome of the changes in the affairs of the Cancer Research Campaign (until lately the British Empire Cancer Campaign for Research) is to be a new format for its annual report: the fat grey volume for 1969 just published1 is to be the last of its kind. This change will be welcome if the new style enables the reader to find more easily the important and significant advances by the institutions and individuals supported by the Campaign and if contributions can be set in a meaningful context of worldwide cancer research. In an area as complex as cancer research, there is always a need for two quite different types of individual: the one who looks for basic truths in specially developed model systems designed to overcome the tiresome fact of biological variation; and the other, the tireless observer, who is content to observe and record the seemingly infinite number of different patterns of web which Nature weaves as a corollary of the principle of natural selection. The two are in complementary, and advance knowledge depends At present, on a proper balance between the two. studies in molecular biology in relation to cancer suffer because of an excess of the first kind of worker.
survival based
on
Tyne, R. J. Scothorne2 reports that histoincompatible intramuscular thyroid grafts were rejected by mice bearing skin-grafts from the same donor, but survived in mice without skingrafts. Survival in the second case is likely to be due to failure of the afferent limb of the homograft reaction. Similar experiments indicated that intratesticular grafts survived even in mice bearing immunising skingrafts, suggesting a failure in the efferent limb, probably dependent on the paucity of lymphatic From Newcastle upon
vessels in the testis. The absence of immunoblasts in the lymphatic vessels draining the pregnant uterus is consistent with the hypothesis that the lumen of uterus is an immunologically privileged site. C. Rudenstam and others3 find that the risk of metastasis is increased when the thoracic duct of a rat bearing a benzpyrene-induced sarcoma in the hind leg is drained for a period of six days before amputation of the affected limb. They claim that the responsible of the thoracic lymph is in the y-globulin component fraction. In the past, inhibition of tumour growth has been the criterion in most screening tests of potential chemotherapeutic agents for cancer. Several attempts have been made to develop screening systems in which the ability of a test substance to inhibit metastasis could be detected. Progress along these lines is now reported 4 in experiments with two transplantable hamster lymphomas, of which one metastasises and the other does not. In the case of the metastasising lymphoma, the frequency of metastasis increased and decreased pari passu with the effects of chemical treatment on the primary tumour graft. Treatment with 5-aziridino-2, 1. 47th Annual Report of the British Empire Cancer Campaign for Research covering the year 1969. The Campaign’s offices are at 2 Carlton House Terrace, London S.W.1. 2. Scothorne, R. J. Rep. Br. Emp. Cancer Campn, 1969, 47, 298. 3. Rudenstam, C., Proctor, J., Alexander, P. ibid. p. 84. 4. Carter, R. L., Mitchley, B. C. V. ibid. p. 52.
140
4-dinitrobenzamide (CB 1954) or with actinomycin D at certain dose levels, however, actually favoured metastasis by the non-metastasising lymphoma. J. Marchant5 reports that the administration of antilymphocyte serum at the time of injection of methylcholanthrene into mice reduced the incidence of sarcoma at the site of injection of methylcholanthrene. This result is the opposite to that expected in the light of the enhancement of carcinogenic response by thymectomy and to that observed by R. K. Gershon and R. L. Carter 6-namely, increased growth at the subcutaneous inoculation site and stimulation of metastasis when antilymphocyte serum is given to hamsters bearing grafts of a normally non-metastasising
tumorigenic effects of a carcinogen of the polycyclic aromatic hydrocarbon type. Basic inquiries of these kinds will, it is to be hoped, provide much-needed
lymphoma.
tains
Other observations by Marchant7 also stand out the trend. It has become fashionable to discover un-host-like antigens in primary neoplasms. Marchant’s failure to discover immunogenic properties in spontaneous reticular or mammary tumours of putatively non-viral origin in mice emphasises that the existence of exploitable immunological differences between host and tumour should not be
against
presumed. I. A. Evans and her colleagues8 in Bangor, from their work on the carcinogenecity of bracken, believe the toxic principle has an empirical formula of C7Hs04, with a carboxylic-acid group in its molecule, but no benzene ring. Dominant lethal mutations, malignant lymphoma, and neoplasms of lung, liver, and gastrointestinal tract have been induced by giving this substance to mice. Furthermore, there is evidence of transfer of a carcinogenic principle from mothers to their progeny via the placenta and/or the milk. The development of a method for detecting the active compound chromatographically has made it possible to look for it in cow’s milk and in foods consumed in Japan, where a very high risk of cancer of the stomach may be related to the consumption of bracken. Brackens of varieties consumed in Japan have been shown to induce cancers in rats, and the carcinogenic principle has been demonstrated by chromatography in the canned product’Warabi ’. There is an increasing awareness of the possible influence of gut flora and of the enzymes they produce on nutrition and on the activity of drugs and in relation to carcinogenecity.9The role of gut flora in converting a non-carcinogenic precursor in cycad meal to an active carcinogen is well known.1o New findings in the United States 11 point to differences between germfree and conventionally maintained rats in the way they metabolise the carcinogen, N-hydroxy-N-2-fluorenylacetamide. Work in this country 12 has shown that germ-free status may, under certain circumstances, dramatically reduce the susceptibility of mice to the Marchant, J. ibid. p. 280. Gershon, R. K., Carter, R. L. Nature, Lond. 1970, 226, 368. Marchant, J. Rep. Br. Emp. Cancer Campn, 1969, 47, 279. Evans, I. A., Barber, G. D., Jones, R. S., Leach, H. ibid. p. 446. 9. Lancet, 1970, i, 552. 10. Laqueur, G. L., McDaniel, E. G., Matsumoto, H. J. natn. Cancer Inst. 1967, 39, 355. 11. Grantham, P. H., Horton, R. E., Weisburger, E. K., Weisburger, J. H. Biochem. Pharmacol. 1970, 19, 163. 12. Grant, G. A., Roe, F. J. C. Rep. Br. Emp. Cancer Campn, 1969, 47, 35. 5. 6. 7. 8.
clues
to
the causation of
gastrointestinal
cancers.
THE CAROTID BODY THE carotid body, that small lobulated structure at the fork of the common carotid artery, consists of groups of cells, surrounded by cellular fibrous tissue, with a rich supply of blood-vessels and nerves. It contwo types of parenchymal cell : the type-l or chief and the slightly less numerous type-li or sustentacell, cular cell. The chief cells show some variation in depth of staining of their cytoplasm and have been subdivided into light and dark cells. Sustentacular cells have long processes which envelop the surface of the chief cells and separate them from the adjacent capillaries.1 Bloodflow through the carotid body, per unit of tissue, is greater than in any other organ of the body, being about forty times that of the heart and four times that of the thyroid.2
Debate continues about the origin and function of the carotid body.3 It is a chemoreceptor organ, and one main physiological function is to respond to a low blood-oxygen tension. Apart from the rare carotidbody tumour, little is known of pathological changes in the organ. Chemical analysis has demonstrated the presence of catecholamines and noradrenaline in the carotid body and its tumourS,4and the chief cells, both normal and neoplastic, have been shown by studies of ultrastructure to contain abundant granules of catecholamine type.5 6
noted that the carotid bodies were significantly larger in people living at high altitudes than in those living at sea level, though there were no differences in histological characteristics. As this observation suggested that sustained hypoxia resulted in hyperplasia, Heath et al. examined the carotid bodies in patients dying of respiratory disease. They studied the carotid bodies in 40 successive necropsies-an unselected group that included 9 cases of emphysema, 2 of cor pulmonale, and 1 of the pickwickian syndrome. The carotid bodies were carefully dissected out and weighed, and a detailed histological examination and differential cell-counts were performed on 21 specimens. In every case the heart was dissected8 to obtain the weights of the right and left ventricles. The weights of the two carotid bodies together ranged from 4-7 mg. to 84-8 mg. with a mean combined weight of 24-2 mg. There was no correlation between the patients’ age and carotid-body weight. In the patients with emphysema the mean weight of Arias-Stella
1. 2. 3. 4. 5. 6. 7. 8.
Grimley, P. M., Glenner, G. G. Circulation, 1968, 37, 648. Bell, G. H., Davidson, J. N., Scarborough, H. Textbook of Physiology and Biochemistry. London, 1968. Karnauchow, P. N. Can. med. Ass. J. 1965, 92, 1298. Pryse-Davies, J., Dawson, I. M. P., Westbury, G. Cancer, N.Y. 1964, 17, 185. Grimley, P. M., Glenner, G. G. ibid. 1967, 20, 1473. Arias-Stella, J. Am. J. Path. 1969, 55, 82a. Heath, D., Edwards, C., Harris, P. Thorax, 1970, 25, 129. Fulton, R. M., Hutchinson, E. C., Jones, A. M. Br. Heart J. 1952, 14, 413.