- Email: [email protected]
ABORTION: THE UNITED STATES SUPREME COURT DECISION
301
they are with the Burkitt lymphoma .25 The frequency in Africa apparently lessens with distance from this focus, though the decline is not uniform. 22 There is also a tendency for the more atypical cases to occur in areas more distant from the focus.22 A suggested connection with onchocerciasis could not be confirmed and-at least if tropical ulcer// sarcoma,
as
of the skin is taken as indicative of traumatically determined cancer-there is no relation between trauma and Kaposi’s sarcoma. 25 As to aetiology, a viral causation has long been mooted; but there is no direct evidence and no real epidemiological evidence to suggest spread by an infectious agent. This may be because no-one has examined the distribution of the disease in space and time; TAYLOR et al. suggest 25 that this sort of work would be most profitable in a stable rural African community rather than in the bustling cities where most medical schools are located. Material from French and African patients with Kaposi’s sarcoma has, however, been examined from the virological viewpoint by GIRALDO et al.,30,31 with most interesting results. These workers established 51 cell-lines in continuous culture from 40 cases of Kaposi’s sarcoma, and some have been continuously propagated for 1-1years. 25 of these cell-lines were derived from tumour-nodule biopsy specimens, 16 from lymph-nodes draining limbs in which there were nodules, and 10 from normal skin. The long-term cultures had irregular growth patterns of either fibroblastoid cells or cells with an epithelioid pattern, and the cells did not exhibit contact inhibition. Considerable pleomorphism was seen in the cultures, but electronmicroscopy revealed herpesvirus particles in 5 of 8 lines examined; in another line, in which the cells were more of the epithelioid type (the herpesvirus lines were fibroblastoid or had undergone a change to a cell which seemed to have some macrophage characteriscancer
tics), cytomegalovirus was present. Preliminary immunological testing indicated that the herpesvirus had antigens in common with Epstein-Barr virus, but to low titre; the virus has yet to be identified fully. All the Kaposi’s sarcoma cases in which virus particles were seen came from Uganda or Zaire. These results
of great interest, but much more information is needed. The ease with which long-term cultures were obtained gives hope that the investigations will quickly be repeated. It will be no surprise if a herpesvirus is involved, since the number of herpesviruses which seem to be oncogenic-at least in certain species-seems to mount monthly. One investigation is displaying some disconcerting features, not least to the experimentalist, 30
are
Giraldo, G., Beth, E., Coeur, P., Vogel, C. L., Dhru, Cancer Inst. 1972, 49, 1495. 31. Giraldo, G., Beth, E., Haguenau, F. ibid. p. 1509.
D.
S. J.
natn.
for HUNT et al.32 record that while all of 12 marmosets with Herpesvirus ateles died of a lymphoblastic leucosarcoma in 26-30 days, a non-injected but caged marmoset died with identical lesions on the 86th day and Herpesvirus ateles was isolated from the lesions. Just how this marmoset became infected is not clear. Thus it will not be surprising if a herpesvirus is involved in production of Kaposi’s sarcoma. Many have thought of the tumour as basically a disease of the reticuloendothelial system, and, in Caucasians at least, it is often complicated by other lymphomas, notably Hodgkin’s disease. Why this does not happen more often in Africans is part of the mystery.
ABORTION: THE UNITED STATES SUPREME
COURT DECISION ABORTION-LAW reform in the United States started later than in the U.K. but proceeded faster and further. In four States it reached total repeal of the existing abortion laws in 1970. In these States abortion is available on request-that is, on the free decision of the woman and one medical practitioner of her choice, and with the minimum of administrative restrictions.
The fundamental question in all abortion legislation is the degree of control which the community or Government should exert over the wishes of the pregnant woman herself. In Britain only Parliament can decide this issue. The United States has a constitution guaranteeing certain freedoms, and a citizen can challenge any part of his State’s legislation which he feels curtails or restricts these rights. This has now been done, and on Jan. 22 the United States Supreme Court ruled that the abortion laws of the State of Texas (enacted 1857, amended 1911) and of Georgia (1968) are unconstitutional and therefore invalid because they imposed restrictions upon the rights of the pregnant woman.33 A final ruling of the Supreme Court, such as has now been given, can for all practical purposes be regarded as concluding the issue. The basic principles laid down by the Court are as follows: "
For the stage prior to approximately the end of the trimester, the abortion decision and its effectuation must be left to the medical judgment of the pregnant woman’s attending physician. " For the stage subsequent to approximately the end of the first trimester, the State, in promoting its interest in the health of the mother, may, if it chooses, regulate the abortion procedure in ways that are reasonably related to maternal health. " For the stage subsequent to viability the State, in promoting its interest in the potentiality of human life, may, if it chooses, regulate and even proscribe abortion except where it is necessary, in appropriate medical judgment, for the preservation of the life or health of the mother." first
The result of this ruling is that, while States may legislation to control abortion within the limits
enact
Melendez, L. V., Garcia, F. G., Trum, B. F. ibid. p. 1631. 33. Reports of the Supreme Court of the United States. No. 70-18. 32. Hunt, R. D.,
302 any legislation which purports to impose restrictions inconsistent with these principles is invalid. In this way the rights of the pregnant woman to terminate her pregnancy, within the limits prescribed, are preserved throughout the United States. Already new abortion facilities are opening in States with restrictive laws, and the total number of legal abortions is expected to rise sharply.
prescribed,
In reaching its new ruling the Supreme Court was influenced by ethical and medical considerations. " We need not resolve the difficult question of when life begins. When those trained in the respective disciplines of medicine, philosophy, and theology are unable to arrive at any consensus, the judiciary, at this point in the development of man’s knowledge, is not in a In its position to speculate as to the answer." judgment the Court calls attention to the newer medical techniques, including menstrual extraction and the morning-after pill.
Statistics on live births and registered abortions to residents of New York State demonstrate the benefits which may follow wide application of the new ruling. It is estimated that in 1971 there would have been 150,700 births at the fertility-rate prevailing immediately before the 1970 law reform.34 131,900 babies The concomitant increase in were, in fact, born. abortions registered was 65,000. Thus, at most, 3500 of the observed increase in registered abortions would account for the fall in the birth-rate. In 1972, the number of births fell by a further 15,500 but the registered abortions increased by only 7700. Therefore the major part of the observed decline in the birth-rate in New York has been due to improved contraception, and the overwhelming majority of the legal abortions registered must have taken the place of abortions previously performed illegally. Declines in the mortality and in the hospital admissions for incomplete abortion reported by Tietze and Guttmacher 35 further confirm these findings.
INFORMATION ON ADVERSE REACTIONS TO DRUGS
something unexpected happens in an illness, questions should be asked: What drugs has the patient been taking ? " and " Could it have been caused by one or more of them ? ". Help is often needed to answer the second question. The most reliable answer would obviously be obtained ’by consulting a comprehensive and up-to-date store of information on adverse drug reactions, but until lately most doctors have had to be content with less. WHEr1
two
"
ago an editorial reviewed the sources of information then available, 3and expressed the hope that the Committee on Safety of Drugs would publish more of the data in its adverse reactions register. The Committee on Safety of Medicines, its successor, has now taken an important step in this direction by making available two loose-leaf volumes of extracts 4 years
34. Tietze, C. Family Planning Perspectives, January, 1973. 35. Tietze, C., Guttmacher, A. F. Lancet, Jan. 13, 1973, p. 105. 36. ibid. 1969, i, 34.
from the Register of Adverse Reactions to departof medicine and therapeutics, postgraduate medical centres, medical libraries, and chief pharmacists of hospitals. These edited and selected extracts summarise reported reactions to 626 drugs. For most the of Ecl0 number drugs prescriptions issued in and Wales is stated for 1968, 1969, and 1970, England a estimate of the order of magnitude of giving rough the denominator; but the extracts summarise reports from hospitals as well as from general practice in the whole of the United Kingdom for the period from January, 1964, to Ottober, 1971, so the estimated denominator cannot be directly applied to the extracts. And for drugs used mainly in hospitals EclO figures mean little, even where they can be given. The data must be interpreted quite cautiously and critically in other respects also, as is explained in a prefatory note. Perhaps the most important reasons for caution are that only a small proportion of reactions are reported, and that some are reported selectively. In addition, of course, the recording of an event does not necessarily mean that it is causally related to the drug named in the list.
ments
Many examples could be cited to illustrate the value (and the shortcomings) of this information. Among tricyclic antidepressives, protriptyline stands out for the number of reports of photosensitivity (47), urticaria (20), and other skin reactions (46), in a total of about 200 reports during 3tyears. A comparison of antirheumatic drugs shows interesting differences between their adverse-effects profiles. With phenylbutazone and oxyphenbutazone serious blood disorders accounted for 36% of all reports and for 76% of all reported deaths, while with indomethacin the corresponding proportions were 8% and 24%. Conversely, major gastrointestinal disturbances made up 20% of all reports and 9 °of reported deaths with phenylbutazone and oxyphenbutazone, whereas with indomethacin the proportions were 17% of all reports and 40%of the deaths. Blood disorders are thus more prominent with phenylbutazone and oxyphenbutazone, and gastrointestinal troubles with indomethacin. The differences also suggest the possibility that the less serious effects on the blood and especially on the alimentary tract may be more likely to get reported with phenylbutazone and oxyphenbutazone than with indomethacin. Such differences in reporting make absolute comparisons between drugs very unreliable, and it would be unwise to conclude that indomethacin is much safer than phenylbutazone because it apparently causes rather fewer reported deaths per million prescriptions. The absence in the register of reports of many well-recognised effects indicates that most doctors think them not worth For example, under dexamphetamine reporting. (1-2 million prescriptions in 1970) only 4 reports of Under dihydrocodeine dependence are recorded. (about 1-5 million prescriptions a year) there are 32 reports of nausea and vomiting and 1 of constipationwhen Palmer et al.37 gave 30 mg. of the drug daily to healthy volunteers, nausea and vomiting and constipation each occurred in about 10%. The extracts 37.
Palmer, R. N., Eade, O. E., O’Shea, P. J., Cuthbert, M. F. ibid 1966, ii, 620.
they are with the Burkitt lymphoma .25 The frequency in Africa apparently lessens with distance from this focus, though the decline is not uniform. 22 There is also a tendency for the more atypical cases to occur in areas more distant from the focus.22 A suggested connection with onchocerciasis could not be confirmed and-at least if tropical ulcer// sarcoma,
as
of the skin is taken as indicative of traumatically determined cancer-there is no relation between trauma and Kaposi’s sarcoma. 25 As to aetiology, a viral causation has long been mooted; but there is no direct evidence and no real epidemiological evidence to suggest spread by an infectious agent. This may be because no-one has examined the distribution of the disease in space and time; TAYLOR et al. suggest 25 that this sort of work would be most profitable in a stable rural African community rather than in the bustling cities where most medical schools are located. Material from French and African patients with Kaposi’s sarcoma has, however, been examined from the virological viewpoint by GIRALDO et al.,30,31 with most interesting results. These workers established 51 cell-lines in continuous culture from 40 cases of Kaposi’s sarcoma, and some have been continuously propagated for 1-1years. 25 of these cell-lines were derived from tumour-nodule biopsy specimens, 16 from lymph-nodes draining limbs in which there were nodules, and 10 from normal skin. The long-term cultures had irregular growth patterns of either fibroblastoid cells or cells with an epithelioid pattern, and the cells did not exhibit contact inhibition. Considerable pleomorphism was seen in the cultures, but electronmicroscopy revealed herpesvirus particles in 5 of 8 lines examined; in another line, in which the cells were more of the epithelioid type (the herpesvirus lines were fibroblastoid or had undergone a change to a cell which seemed to have some macrophage characteriscancer
tics), cytomegalovirus was present. Preliminary immunological testing indicated that the herpesvirus had antigens in common with Epstein-Barr virus, but to low titre; the virus has yet to be identified fully. All the Kaposi’s sarcoma cases in which virus particles were seen came from Uganda or Zaire. These results
of great interest, but much more information is needed. The ease with which long-term cultures were obtained gives hope that the investigations will quickly be repeated. It will be no surprise if a herpesvirus is involved, since the number of herpesviruses which seem to be oncogenic-at least in certain species-seems to mount monthly. One investigation is displaying some disconcerting features, not least to the experimentalist, 30
are
Giraldo, G., Beth, E., Coeur, P., Vogel, C. L., Dhru, Cancer Inst. 1972, 49, 1495. 31. Giraldo, G., Beth, E., Haguenau, F. ibid. p. 1509.
D.
S. J.
natn.
for HUNT et al.32 record that while all of 12 marmosets with Herpesvirus ateles died of a lymphoblastic leucosarcoma in 26-30 days, a non-injected but caged marmoset died with identical lesions on the 86th day and Herpesvirus ateles was isolated from the lesions. Just how this marmoset became infected is not clear. Thus it will not be surprising if a herpesvirus is involved in production of Kaposi’s sarcoma. Many have thought of the tumour as basically a disease of the reticuloendothelial system, and, in Caucasians at least, it is often complicated by other lymphomas, notably Hodgkin’s disease. Why this does not happen more often in Africans is part of the mystery.
ABORTION: THE UNITED STATES SUPREME
COURT DECISION ABORTION-LAW reform in the United States started later than in the U.K. but proceeded faster and further. In four States it reached total repeal of the existing abortion laws in 1970. In these States abortion is available on request-that is, on the free decision of the woman and one medical practitioner of her choice, and with the minimum of administrative restrictions.
The fundamental question in all abortion legislation is the degree of control which the community or Government should exert over the wishes of the pregnant woman herself. In Britain only Parliament can decide this issue. The United States has a constitution guaranteeing certain freedoms, and a citizen can challenge any part of his State’s legislation which he feels curtails or restricts these rights. This has now been done, and on Jan. 22 the United States Supreme Court ruled that the abortion laws of the State of Texas (enacted 1857, amended 1911) and of Georgia (1968) are unconstitutional and therefore invalid because they imposed restrictions upon the rights of the pregnant woman.33 A final ruling of the Supreme Court, such as has now been given, can for all practical purposes be regarded as concluding the issue. The basic principles laid down by the Court are as follows: "
For the stage prior to approximately the end of the trimester, the abortion decision and its effectuation must be left to the medical judgment of the pregnant woman’s attending physician. " For the stage subsequent to approximately the end of the first trimester, the State, in promoting its interest in the health of the mother, may, if it chooses, regulate the abortion procedure in ways that are reasonably related to maternal health. " For the stage subsequent to viability the State, in promoting its interest in the potentiality of human life, may, if it chooses, regulate and even proscribe abortion except where it is necessary, in appropriate medical judgment, for the preservation of the life or health of the mother." first
The result of this ruling is that, while States may legislation to control abortion within the limits
enact
Melendez, L. V., Garcia, F. G., Trum, B. F. ibid. p. 1631. 33. Reports of the Supreme Court of the United States. No. 70-18. 32. Hunt, R. D.,
302 any legislation which purports to impose restrictions inconsistent with these principles is invalid. In this way the rights of the pregnant woman to terminate her pregnancy, within the limits prescribed, are preserved throughout the United States. Already new abortion facilities are opening in States with restrictive laws, and the total number of legal abortions is expected to rise sharply.
prescribed,
In reaching its new ruling the Supreme Court was influenced by ethical and medical considerations. " We need not resolve the difficult question of when life begins. When those trained in the respective disciplines of medicine, philosophy, and theology are unable to arrive at any consensus, the judiciary, at this point in the development of man’s knowledge, is not in a In its position to speculate as to the answer." judgment the Court calls attention to the newer medical techniques, including menstrual extraction and the morning-after pill.
Statistics on live births and registered abortions to residents of New York State demonstrate the benefits which may follow wide application of the new ruling. It is estimated that in 1971 there would have been 150,700 births at the fertility-rate prevailing immediately before the 1970 law reform.34 131,900 babies The concomitant increase in were, in fact, born. abortions registered was 65,000. Thus, at most, 3500 of the observed increase in registered abortions would account for the fall in the birth-rate. In 1972, the number of births fell by a further 15,500 but the registered abortions increased by only 7700. Therefore the major part of the observed decline in the birth-rate in New York has been due to improved contraception, and the overwhelming majority of the legal abortions registered must have taken the place of abortions previously performed illegally. Declines in the mortality and in the hospital admissions for incomplete abortion reported by Tietze and Guttmacher 35 further confirm these findings.
INFORMATION ON ADVERSE REACTIONS TO DRUGS
something unexpected happens in an illness, questions should be asked: What drugs has the patient been taking ? " and " Could it have been caused by one or more of them ? ". Help is often needed to answer the second question. The most reliable answer would obviously be obtained ’by consulting a comprehensive and up-to-date store of information on adverse drug reactions, but until lately most doctors have had to be content with less. WHEr1
two
"
ago an editorial reviewed the sources of information then available, 3and expressed the hope that the Committee on Safety of Drugs would publish more of the data in its adverse reactions register. The Committee on Safety of Medicines, its successor, has now taken an important step in this direction by making available two loose-leaf volumes of extracts 4 years
34. Tietze, C. Family Planning Perspectives, January, 1973. 35. Tietze, C., Guttmacher, A. F. Lancet, Jan. 13, 1973, p. 105. 36. ibid. 1969, i, 34.
from the Register of Adverse Reactions to departof medicine and therapeutics, postgraduate medical centres, medical libraries, and chief pharmacists of hospitals. These edited and selected extracts summarise reported reactions to 626 drugs. For most the of Ecl0 number drugs prescriptions issued in and Wales is stated for 1968, 1969, and 1970, England a estimate of the order of magnitude of giving rough the denominator; but the extracts summarise reports from hospitals as well as from general practice in the whole of the United Kingdom for the period from January, 1964, to Ottober, 1971, so the estimated denominator cannot be directly applied to the extracts. And for drugs used mainly in hospitals EclO figures mean little, even where they can be given. The data must be interpreted quite cautiously and critically in other respects also, as is explained in a prefatory note. Perhaps the most important reasons for caution are that only a small proportion of reactions are reported, and that some are reported selectively. In addition, of course, the recording of an event does not necessarily mean that it is causally related to the drug named in the list.
ments
Many examples could be cited to illustrate the value (and the shortcomings) of this information. Among tricyclic antidepressives, protriptyline stands out for the number of reports of photosensitivity (47), urticaria (20), and other skin reactions (46), in a total of about 200 reports during 3tyears. A comparison of antirheumatic drugs shows interesting differences between their adverse-effects profiles. With phenylbutazone and oxyphenbutazone serious blood disorders accounted for 36% of all reports and for 76% of all reported deaths, while with indomethacin the corresponding proportions were 8% and 24%. Conversely, major gastrointestinal disturbances made up 20% of all reports and 9 °of reported deaths with phenylbutazone and oxyphenbutazone, whereas with indomethacin the proportions were 17% of all reports and 40%of the deaths. Blood disorders are thus more prominent with phenylbutazone and oxyphenbutazone, and gastrointestinal troubles with indomethacin. The differences also suggest the possibility that the less serious effects on the blood and especially on the alimentary tract may be more likely to get reported with phenylbutazone and oxyphenbutazone than with indomethacin. Such differences in reporting make absolute comparisons between drugs very unreliable, and it would be unwise to conclude that indomethacin is much safer than phenylbutazone because it apparently causes rather fewer reported deaths per million prescriptions. The absence in the register of reports of many well-recognised effects indicates that most doctors think them not worth For example, under dexamphetamine reporting. (1-2 million prescriptions in 1970) only 4 reports of Under dihydrocodeine dependence are recorded. (about 1-5 million prescriptions a year) there are 32 reports of nausea and vomiting and 1 of constipationwhen Palmer et al.37 gave 30 mg. of the drug daily to healthy volunteers, nausea and vomiting and constipation each occurred in about 10%. The extracts 37.
Palmer, R. N., Eade, O. E., O’Shea, P. J., Cuthbert, M. F. ibid 1966, ii, 620.